Miriam E. Tucker

A Food and Drug Administration advisory panel has voted narrowly to recommend approval of the monoclonal antibody teplizumab (Tzield, Provention Bio) for the delay of type 1 diabetes in at-risk individuals.

The 10-7 vote of the FDA’s endocrinologic and metabolic drugs advisory committee on May 27 reflected a difficult decision-making process on the part of many members to weigh the benefits of a potential 2-year delay in the onset of type 1 diabetes against both observed and theoretical risks, as well as what most considered to be insufficient data.

Regardless of their vote, nearly all panel members advised the FDA that the company should be required to conduct at least one additional larger long-term efficacy and safety trial to satisfy what they felt were major gaps in the data. Some advised that use of the drug be restricted to a very narrow group of recipients until efficacy and safety can be better established.

If approved, teplizumab, which interferes with T cell–mediated autoimmune destruction of pancreatic beta cells, would be the first disease-modifying therapy for impeding progression of type 1 diabetes. The proposed indication is for individuals who have two or more type 1 diabetes-associated autoantibodies and subclinical dysglycemia.

That “stage 2” or “at-risk” condition is associated with a nearly 100% lifetime risk of progression to clinical (“stage 3”) type 1 diabetes and a 75% risk of developing the disease within 5 years. As of now, most such individuals are first-degree relatives of people with type 1 diabetes identified through TrialNet.
 

What’s the evidence to support approval so far?

In 2019, a pivotal phase 2 randomized, placebo-controlled TN-10 trial involving 76 at-risk children and adults ages 8 years and older showed that a single 14-day treatment of daily intravenous infusions of teplizumab in 44 patients resulted in a significant median 2-year delay to onset of clinical type 1 diabetes, compared with 32 who received placebo. Further follow-up data continue to show that fewer patients who received teplizumab have progressed to clinical type 1 diabetes.

While most advisory panelists agreed that the TN-10 study demonstrated efficacy, several also said that the sample size was insufficient and at least one additional randomized trial should be conducted to replicate the findings.

Although the FDA typically requires companies to demonstrate a drug’s effectiveness with at least two separate clinical trials, the agency allows companies to substitute other forms of data for a second randomized clinical trial, such as study results for the drug in a closely related condition, mechanistic data, or knowledge of other drugs from the same class.

In this case, Provention’s submission included as “confirmatory” evidence a meta-analysis of data from five earlier randomized trials (three placebo controlled, two open label) of a total 942 individuals with newly diagnosed type 1 diabetes (“stage 3”) who received either one or two 14-day teplizumab courses (n = 729) or placebo. These showed consistent preservation of C-peptide, a surrogate marker of beta-cell function, along with lower mean insulin use.

Several panel members expressed dissatisfaction with those confirmatory data, noting the patient population was different from those for which the company is currently seeking the indication, and that C-peptide is an inadequate endpoint for demonstrating efficacy.
 

Safety: Adverse events mostly transient, but unanswered questions

Adverse events reported in at least 10% of teplizumab recipients included lymphopenia (76.8% vs. 9.4% placebo; relative risk, 8.2), leukopenia (82.1% vs. 24.1%; RR, 3.4), and rash (44.5% vs. 9.0%; RR, 4.9).

“Most adverse events related to teplizumab were mechanism-based, predictable, transient, and manageable,” Chief Medical Officer of Provention Bio, Eleanor Ramos, MD, said.

Among other safety issues that concerned the panel, diabetic ketoacidosis (DKA) was seen in 2.3% of 773 teplizumab recipients with new-onset type 1 diabetes versus just 1% among the 245 controls, a significant, nearly sixfold increase. No DKA occurred in the TN-10 trial. No clear explanation was offered for the imbalance in the meta-analysis.

Cytokine release syndrome occurred in 0.6% of patients who received teplizumab versus no controls, and infections in 3.4% versus 2.0%, respectively.

Approximately 10% of patients were not able to complete the treatment course because of protocol-directed withdrawal criteria, which included elevations in bilirubin or liver enzymes, or drops in platelet count, neutrophils, or hemoglobin, FDA reviewer Lauren Wood Heickman, MD, noted.

There was only one malignancy, a melanoma in a patient with a preexisting lesion, but malignancy is a theoretical concern with long-term immunosuppression, Dr. Heickman said.

Despite the concerns about the data, panel members expressed unanimous appreciation for the 18 people who spoke during public comments attesting to the lifelong burdens involved in living with type 1 diabetes who urged the FDA to approve teplizumab.

Many of them noted that even a 2-year reprieve from the burden of constant attention to managing blood glucose can make a major difference in the life of a young person. The speakers included physicians, parents of children with type 1 diabetes, adults who have the condition themselves and who worry about their children getting it, and researchers in the field.
 

Panel members describe ‘struggle’ with vote decision

Panel member Michael Blaha, MD, of Johns Hopkins University, Baltimore, voted in favor of teplizumab approval. However, he said, “I was very conflicted on this one and my ‘yes’ is very qualified. In my opinion the risk-benefit is very narrow, and I would only approve this drug for the exact indication of the trial. ... Patients who don’t fit the criteria could hopefully be enrolled in a second confirmatory trial.”

He also advised an extensive Risk Evaluation and Mitigation Strategies program to look for both short- and long-term adverse effects.

“My overall take on this is that I do think it’s a promising paradigm-shifting therapy that really needs to move forward, at least scientifically. I’m excited about it, but I have a lot of skepticism about the entire body of data to make any more than the most narrow of approval,” Dr. Blaha said.  

Susan S. Ellenberg, PhD, professor of biostatistics, medical ethics, and health policy at the University of Pennsylvania, Philadelphia, voted yes but also with difficulty.

“I really struggled with it. ... I was pushed by the very encouraging results of what is admittedly a very small study and something I can’t feel is completely definitive. But I would not like to deny the kind of people that we heard from today the opportunity to weigh their own risks and benefits to try this. And I would certainly agree that a very, very rigorous postmarketing program, preferably including another controlled trial, should be carried out.”

But David M. Nathan, MD, director of the Diabetes Center and Clinical Research Center, Massachusetts General Hospital, Boston, voted no.

“I struggled with this vote, tremendously, having listened carefully to the patients with type 1 diabetes ... but that said, having done clinical research for 40 years in type 1 diabetes, I think we need more data, both in terms of efficacy and of safety. I would hate a number of years down the road to figure out that we actually caused more harm than good, especially keeping in mind that the treatment of type 1 diabetes is evolving rapidly.”

A different perspective came from Mara L. Becker, MD, vice chair of the department of pediatric rheumatology at Duke University, Durham, N.C. She voted yes, pointing out that she’s accustomed to prescribing biologics for chronic conditions in children.

“I was unconflicted in my vote, which was yes. I thought the data ... were convincing and the need is great. I would support a label for children [aged 8 years] and older with at least stage 2 disease ... and I would require postmarketing safety surveillance to understand what the long-term side effects could be, but I would still be in favor of it.”

FDA advisory panel committee members are vetted for conflicts of interest and waivers granted for participation if necessary; none were granted for this meeting.

A version of this article first appeared on Medscape.com.

A Food and Drug Administration advisory panel has voted narrowly to recommend approval of the monoclonal antibody teplizumab (Tzield, Provention Bio) for the delay of type 1 diabetes in at-risk individuals.

The 10-7 vote of the FDA’s endocrinologic and metabolic drugs advisory committee on May 27 reflected a difficult decision-making process on the part of many members to weigh the benefits of a potential 2-year delay in the onset of type 1 diabetes against both observed and theoretical risks, as well as what most considered to be insufficient data.

Regardless of their vote, nearly all panel members advised the FDA that the company should be required to conduct at least one additional larger long-term efficacy and safety trial to satisfy what they felt were major gaps in the data. Some advised that use of the drug be restricted to a very narrow group of recipients until efficacy and safety can be better established.

If approved, teplizumab, which interferes with T cell–mediated autoimmune destruction of pancreatic beta cells, would be the first disease-modifying therapy for impeding progression of type 1 diabetes. The proposed indication is for individuals who have two or more type 1 diabetes-associated autoantibodies and subclinical dysglycemia.

That “stage 2” or “at-risk” condition is associated with a nearly 100% lifetime risk of progression to clinical (“stage 3”) type 1 diabetes and a 75% risk of developing the disease within 5 years. As of now, most such individuals are first-degree relatives of people with type 1 diabetes identified through TrialNet.
 

What’s the evidence to support approval so far?

In 2019, a pivotal phase 2 randomized, placebo-controlled TN-10 trial involving 76 at-risk children and adults ages 8 years and older showed that a single 14-day treatment of daily intravenous infusions of teplizumab in 44 patients resulted in a significant median 2-year delay to onset of clinical type 1 diabetes, compared with 32 who received placebo. Further follow-up data continue to show that fewer patients who received teplizumab have progressed to clinical type 1 diabetes.

While most advisory panelists agreed that the TN-10 study demonstrated efficacy, several also said that the sample size was insufficient and at least one additional randomized trial should be conducted to replicate the findings.

Although the FDA typically requires companies to demonstrate a drug’s effectiveness with at least two separate clinical trials, the agency allows companies to substitute other forms of data for a second randomized clinical trial, such as study results for the drug in a closely related condition, mechanistic data, or knowledge of other drugs from the same class.

In this case, Provention’s submission included as “confirmatory” evidence a meta-analysis of data from five earlier randomized trials (three placebo controlled, two open label) of a total 942 individuals with newly diagnosed type 1 diabetes (“stage 3”) who received either one or two 14-day teplizumab courses (n = 729) or placebo. These showed consistent preservation of C-peptide, a surrogate marker of beta-cell function, along with lower mean insulin use.

Several panel members expressed dissatisfaction with those confirmatory data, noting the patient population was different from those for which the company is currently seeking the indication, and that C-peptide is an inadequate endpoint for demonstrating efficacy.
 

Safety: Adverse events mostly transient, but unanswered questions

Adverse events reported in at least 10% of teplizumab recipients included lymphopenia (76.8% vs. 9.4% placebo; relative risk, 8.2), leukopenia (82.1% vs. 24.1%; RR, 3.4), and rash (44.5% vs. 9.0%; RR, 4.9).

“Most adverse events related to teplizumab were mechanism-based, predictable, transient, and manageable,” Chief Medical Officer of Provention Bio, Eleanor Ramos, MD, said.

Among other safety issues that concerned the panel, diabetic ketoacidosis (DKA) was seen in 2.3% of 773 teplizumab recipients with new-onset type 1 diabetes versus just 1% among the 245 controls, a significant, nearly sixfold increase. No DKA occurred in the TN-10 trial. No clear explanation was offered for the imbalance in the meta-analysis.

Cytokine release syndrome occurred in 0.6% of patients who received teplizumab versus no controls, and infections in 3.4% versus 2.0%, respectively.

Approximately 10% of patients were not able to complete the treatment course because of protocol-directed withdrawal criteria, which included elevations in bilirubin or liver enzymes, or drops in platelet count, neutrophils, or hemoglobin, FDA reviewer Lauren Wood Heickman, MD, noted.

There was only one malignancy, a melanoma in a patient with a preexisting lesion, but malignancy is a theoretical concern with long-term immunosuppression, Dr. Heickman said.

Despite the concerns about the data, panel members expressed unanimous appreciation for the 18 people who spoke during public comments attesting to the lifelong burdens involved in living with type 1 diabetes who urged the FDA to approve teplizumab.

Many of them noted that even a 2-year reprieve from the burden of constant attention to managing blood glucose can make a major difference in the life of a young person. The speakers included physicians, parents of children with type 1 diabetes, adults who have the condition themselves and who worry about their children getting it, and researchers in the field.
 

Panel members describe ‘struggle’ with vote decision

Panel member Michael Blaha, MD, of Johns Hopkins University, Baltimore, voted in favor of teplizumab approval. However, he said, “I was very conflicted on this one and my ‘yes’ is very qualified. In my opinion the risk-benefit is very narrow, and I would only approve this drug for the exact indication of the trial. ... Patients who don’t fit the criteria could hopefully be enrolled in a second confirmatory trial.”

He also advised an extensive Risk Evaluation and Mitigation Strategies program to look for both short- and long-term adverse effects.

“My overall take on this is that I do think it’s a promising paradigm-shifting therapy that really needs to move forward, at least scientifically. I’m excited about it, but I have a lot of skepticism about the entire body of data to make any more than the most narrow of approval,” Dr. Blaha said.  

Susan S. Ellenberg, PhD, professor of biostatistics, medical ethics, and health policy at the University of Pennsylvania, Philadelphia, voted yes but also with difficulty.

“I really struggled with it. ... I was pushed by the very encouraging results of what is admittedly a very small study and something I can’t feel is completely definitive. But I would not like to deny the kind of people that we heard from today the opportunity to weigh their own risks and benefits to try this. And I would certainly agree that a very, very rigorous postmarketing program, preferably including another controlled trial, should be carried out.”

But David M. Nathan, MD, director of the Diabetes Center and Clinical Research Center, Massachusetts General Hospital, Boston, voted no.

“I struggled with this vote, tremendously, having listened carefully to the patients with type 1 diabetes ... but that said, having done clinical research for 40 years in type 1 diabetes, I think we need more data, both in terms of efficacy and of safety. I would hate a number of years down the road to figure out that we actually caused more harm than good, especially keeping in mind that the treatment of type 1 diabetes is evolving rapidly.”

A different perspective came from Mara L. Becker, MD, vice chair of the department of pediatric rheumatology at Duke University, Durham, N.C. She voted yes, pointing out that she’s accustomed to prescribing biologics for chronic conditions in children.

“I was unconflicted in my vote, which was yes. I thought the data ... were convincing and the need is great. I would support a label for children [aged 8 years] and older with at least stage 2 disease ... and I would require postmarketing safety surveillance to understand what the long-term side effects could be, but I would still be in favor of it.”

FDA advisory panel committee members are vetted for conflicts of interest and waivers granted for participation if necessary; none were granted for this meeting.

A version of this article first appeared on Medscape.com.

A Food and Drug Administration advisory panel has voted narrowly to recommend approval of the monoclonal antibody teplizumab (Tzield, Provention Bio) for the delay of type 1 diabetes in at-risk individuals.

The 10-7 vote of the FDA’s endocrinologic and metabolic drugs advisory committee on May 27 reflected a difficult decision-making process on the part of many members to weigh the benefits of a potential 2-year delay in the onset of type 1 diabetes against both observed and theoretical risks, as well as what most considered to be insufficient data.

Regardless of their vote, nearly all panel members advised the FDA that the company should be required to conduct at least one additional larger long-term efficacy and safety trial to satisfy what they felt were major gaps in the data. Some advised that use of the drug be restricted to a very narrow group of recipients until efficacy and safety can be better established.

If approved, teplizumab, which interferes with T cell–mediated autoimmune destruction of pancreatic beta cells, would be the first disease-modifying therapy for impeding progression of type 1 diabetes. The proposed indication is for individuals who have two or more type 1 diabetes-associated autoantibodies and subclinical dysglycemia.

That “stage 2” or “at-risk” condition is associated with a nearly 100% lifetime risk of progression to clinical (“stage 3”) type 1 diabetes and a 75% risk of developing the disease within 5 years. As of now, most such individuals are first-degree relatives of people with type 1 diabetes identified through TrialNet.
 

What’s the evidence to support approval so far?

In 2019, a pivotal phase 2 randomized, placebo-controlled TN-10 trial involving 76 at-risk children and adults ages 8 years and older showed that a single 14-day treatment of daily intravenous infusions of teplizumab in 44 patients resulted in a significant median 2-year delay to onset of clinical type 1 diabetes, compared with 32 who received placebo. Further follow-up data continue to show that fewer patients who received teplizumab have progressed to clinical type 1 diabetes.

While most advisory panelists agreed that the TN-10 study demonstrated efficacy, several also said that the sample size was insufficient and at least one additional randomized trial should be conducted to replicate the findings.

Although the FDA typically requires companies to demonstrate a drug’s effectiveness with at least two separate clinical trials, the agency allows companies to substitute other forms of data for a second randomized clinical trial, such as study results for the drug in a closely related condition, mechanistic data, or knowledge of other drugs from the same class.

In this case, Provention’s submission included as “confirmatory” evidence a meta-analysis of data from five earlier randomized trials (three placebo controlled, two open label) of a total 942 individuals with newly diagnosed type 1 diabetes (“stage 3”) who received either one or two 14-day teplizumab courses (n = 729) or placebo. These showed consistent preservation of C-peptide, a surrogate marker of beta-cell function, along with lower mean insulin use.

Several panel members expressed dissatisfaction with those confirmatory data, noting the patient population was different from those for which the company is currently seeking the indication, and that C-peptide is an inadequate endpoint for demonstrating efficacy.
 

Safety: Adverse events mostly transient, but unanswered questions

Adverse events reported in at least 10% of teplizumab recipients included lymphopenia (76.8% vs. 9.4% placebo; relative risk, 8.2), leukopenia (82.1% vs. 24.1%; RR, 3.4), and rash (44.5% vs. 9.0%; RR, 4.9).

“Most adverse events related to teplizumab were mechanism-based, predictable, transient, and manageable,” Chief Medical Officer of Provention Bio, Eleanor Ramos, MD, said.

Among other safety issues that concerned the panel, diabetic ketoacidosis (DKA) was seen in 2.3% of 773 teplizumab recipients with new-onset type 1 diabetes versus just 1% among the 245 controls, a significant, nearly sixfold increase. No DKA occurred in the TN-10 trial. No clear explanation was offered for the imbalance in the meta-analysis.

Cytokine release syndrome occurred in 0.6% of patients who received teplizumab versus no controls, and infections in 3.4% versus 2.0%, respectively.

Approximately 10% of patients were not able to complete the treatment course because of protocol-directed withdrawal criteria, which included elevations in bilirubin or liver enzymes, or drops in platelet count, neutrophils, or hemoglobin, FDA reviewer Lauren Wood Heickman, MD, noted.

There was only one malignancy, a melanoma in a patient with a preexisting lesion, but malignancy is a theoretical concern with long-term immunosuppression, Dr. Heickman said.

Despite the concerns about the data, panel members expressed unanimous appreciation for the 18 people who spoke during public comments attesting to the lifelong burdens involved in living with type 1 diabetes who urged the FDA to approve teplizumab.

Many of them noted that even a 2-year reprieve from the burden of constant attention to managing blood glucose can make a major difference in the life of a young person. The speakers included physicians, parents of children with type 1 diabetes, adults who have the condition themselves and who worry about their children getting it, and researchers in the field.
 

Panel members describe ‘struggle’ with vote decision

Panel member Michael Blaha, MD, of Johns Hopkins University, Baltimore, voted in favor of teplizumab approval. However, he said, “I was very conflicted on this one and my ‘yes’ is very qualified. In my opinion the risk-benefit is very narrow, and I would only approve this drug for the exact indication of the trial. ... Patients who don’t fit the criteria could hopefully be enrolled in a second confirmatory trial.”

He also advised an extensive Risk Evaluation and Mitigation Strategies program to look for both short- and long-term adverse effects.

“My overall take on this is that I do think it’s a promising paradigm-shifting therapy that really needs to move forward, at least scientifically. I’m excited about it, but I have a lot of skepticism about the entire body of data to make any more than the most narrow of approval,” Dr. Blaha said.  

Susan S. Ellenberg, PhD, professor of biostatistics, medical ethics, and health policy at the University of Pennsylvania, Philadelphia, voted yes but also with difficulty.

“I really struggled with it. ... I was pushed by the very encouraging results of what is admittedly a very small study and something I can’t feel is completely definitive. But I would not like to deny the kind of people that we heard from today the opportunity to weigh their own risks and benefits to try this. And I would certainly agree that a very, very rigorous postmarketing program, preferably including another controlled trial, should be carried out.”

But David M. Nathan, MD, director of the Diabetes Center and Clinical Research Center, Massachusetts General Hospital, Boston, voted no.

“I struggled with this vote, tremendously, having listened carefully to the patients with type 1 diabetes ... but that said, having done clinical research for 40 years in type 1 diabetes, I think we need more data, both in terms of efficacy and of safety. I would hate a number of years down the road to figure out that we actually caused more harm than good, especially keeping in mind that the treatment of type 1 diabetes is evolving rapidly.”

A different perspective came from Mara L. Becker, MD, vice chair of the department of pediatric rheumatology at Duke University, Durham, N.C. She voted yes, pointing out that she’s accustomed to prescribing biologics for chronic conditions in children.

“I was unconflicted in my vote, which was yes. I thought the data ... were convincing and the need is great. I would support a label for children [aged 8 years] and older with at least stage 2 disease ... and I would require postmarketing safety surveillance to understand what the long-term side effects could be, but I would still be in favor of it.”

FDA advisory panel committee members are vetted for conflicts of interest and waivers granted for participation if necessary; none were granted for this meeting.

A version of this article first appeared on Medscape.com.

Overuse of basal insulin rather than adding therapies that target mealtime glucose levels is a common problem in primary care management of type 2 diabetes that impedes achievement of optimal glycemic control, new research suggests.

Such ‘overbasalization,’ defined as a hemoglobin A1c of greater than 8% despite use of more than 0.5 units/kg per day of basal insulin, was identified in about 40% of patients seen in a Florida primary care clinic during 2015-2018. The findings were published in the April 2021 issue of Clinical Diabetes by Kevin Cowart, PharmD, a diabetes care and education specialist at the University of South Florida, Tampa, and colleagues.

The literature suggests that once people with type 2 diabetes start basal insulin, the chance that they’ll achieve a given hemoglobin A1c target, i.e., less than 7%, diminishes significantly if that goal isn’t achieved within the first year of starting insulin, Dr. Cowart said in an interview.

“Our analysis suggests that overbasalization plays a role in patients with type 2 diabetes on basal insulin not achieving optimal glycemic control. Basal insulin is not designed to address postprandial hyperglycemia. I think there’s a clear need to address hesitancy in therapeutic progression beyond basal insulin. A lot of factors underlie the delays, with therapeutic inertia being one of them. It’s complex,” he said.
 

Overbasalization seen in large proportion of patients

The study comprised 655 adults diagnosed with type 2 diabetes for at least a year who received a prescription for a basal insulin (glargine U-100, glargine U-300, detemir, degludec U-100, degludec U-200, regular U-500, or NPH insulin).

The patients had a mean hemoglobin A1c of 8.4% and a mean basal insulin dose 0.4 units/kg per day. The prevalence of overbasalization was 38.1% for those with hemoglobin A1c above 8%, 42.7% for those with A1c of 9% or above, and 42% with A1c of 10% or greater.

Patient characteristics independently associated with overbasalization were age 35-54 years (odds ratio 1.89), age 65-80 years (0.44), A1c 9% or greater (13.97), and A1c 10% or greater (6.04). Having a prescription for insulin glargine U-100 was associated with a lower overbasalization risk (0.62). In multivariate analysis, only an A1c of 9% or greater remained significant.

Rozalina G. McCoy, MD, an endocrinologist and primary care clinician at the Mayo Clinic, Rochester, Minn., said in an interview that she sees [overbasalization] frequently in patients who are referred to her. “It’s kind of that wall that patients with type 2 diabetes hit because their A1c is high but their fasting blood sugars are normal. Sometimes it’s assumed that there’s a discrepancy, because people don’t always think about postprandial hyperglycemia.”

She also noted that there has been a push in recent years to simplify regimens, particularly in older patients.

“We really want to avoid rapid-acting insulin in older patients because we’re afraid of hypoglycemia, so we start them on basal and keep the noninsulins like metformin and sulfonylureas around. Initially those control the postprandial blood sugar but over time they’re no longer enough.”
 

Options exist for addressing postmeal blood sugar highs while minimizing lows

While in the past adding premeal insulin was the only option, today there are alternatives for addressing postmeal hyperglycemia, at least in the short term.

Dr. Cowart advised that the first step is to have patients self-monitor their blood glucose and titrate their basal insulin to address fasting hyperglycemia first. Once that appropriate dose is reached, if the patient’s hemoglobin A1c is still above target, the next step is to evaluate the need for postmeal control.

For patients who are at high cardiovascular risk, the next step might involve adding a sodium-glucose cotransporter 2 inhibitor (SGLT2i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA) instead of premeal insulin. But for patients in whom overbasalization is the main concern, a GLP-1RA might be the better choice since it will have a greater impact on postprandial glucose levels, while an SGLT2i will have more effect on fasting blood sugar, he said.

Another option is to use a fixed-dose combination of basal insulin and a glucagon-like peptide 1 receptor agonist (GLP-1RA), provided there aren’t cost or formulary barriers. “We want to use the right combination of drugs and not use too much of one to lead to hypoglycemia,” Dr. Cowart said.

Dr. McCoy doesn’t use fixed-dose combinations because they don’t allow as much flexibility in dosing. To correct overbasalization, she also recommends adding either a GLP-1RA or SGLT2i instead of premeal insulin. However, she cautions, “you still have to monitor those patients because after a few years it still won’t be enough and you’ll have to add mealtime insulin.”

If cost or lack of coverage prevents a patient’s use of SLGT2i/GLP-1RAs, Dr. McCoy said that adding just one premeal injection of rapid-acting insulin before the largest meal of the day is one option. Another is to use twice-daily NPH insulin instead of analog basal insulin, since that does offer some postprandial coverage.

Dr. Cowart said his approach in cost barrier situations is to try to use patient assistance programs and to look into the patient’s formulary to see if there is step therapy or tier considerations, and maybe have a discussion with the insurance company. “We often have to navigate that, and it does take a significant amount of time and could potentially delay patients getting the right therapy when it’s warranted. That is an area where there is a particular role for pharmacists in helping to overcome that and get patients on the right drugs,” he explained.
 

Problem may be even more common; testing is key

Dr. McCoy said that the A1c cutoff of 8% used to define overbasalization in the study probably resulted in an underestimation of the problem, since many patients are experiencing nighttime hypoglycemia from the basal insulin. The lows bring down their A1c level, but they’re still experiencing postmeal highs.

“I think they’re missing a lot of people, to be honest. I see a lot of patients with A1cs that aren’t that bad, say 7.5%, and their fasting blood sugars are okay, but if you were to put a [continuous glucose monitor] on those patients, invariably there’s hypoglycemia at night that no one knew about.”

Of course, for insurance reasons, most people with type 2 diabetes don’t currently have access to continuous glucose monitors. And often those who are not taking multiple daily injections are limited to one fingerstick test strip a day.

Dr. McCoy says that if hypoglycemia is a concern she will write a prior authorization justifying more test strips.

“I state explicitly in my notes why I recommend frequent monitoring. If they’re on a sulfonylurea, they should be able to check more frequently because they can have hypoglycemia. Same thing with basal insulin.”

Dr. McCoy advises that patients test their blood sugar 2 hours after the largest meal on one day, and at other times on different days. “Blood glucose after a meal shouldn’t be more than 200 [mg/dL]. If it is, that’s not a failure of basal insulin. It’s doing its job. You just need a different agent.”

Dr. Cowart has no disclosures. Dr. McCoy receives funding from the National Institutes of Health.

Overuse of basal insulin rather than adding therapies that target mealtime glucose levels is a common problem in primary care management of type 2 diabetes that impedes achievement of optimal glycemic control, new research suggests.

Such ‘overbasalization,’ defined as a hemoglobin A1c of greater than 8% despite use of more than 0.5 units/kg per day of basal insulin, was identified in about 40% of patients seen in a Florida primary care clinic during 2015-2018. The findings were published in the April 2021 issue of Clinical Diabetes by Kevin Cowart, PharmD, a diabetes care and education specialist at the University of South Florida, Tampa, and colleagues.

The literature suggests that once people with type 2 diabetes start basal insulin, the chance that they’ll achieve a given hemoglobin A1c target, i.e., less than 7%, diminishes significantly if that goal isn’t achieved within the first year of starting insulin, Dr. Cowart said in an interview.

“Our analysis suggests that overbasalization plays a role in patients with type 2 diabetes on basal insulin not achieving optimal glycemic control. Basal insulin is not designed to address postprandial hyperglycemia. I think there’s a clear need to address hesitancy in therapeutic progression beyond basal insulin. A lot of factors underlie the delays, with therapeutic inertia being one of them. It’s complex,” he said.
 

Overbasalization seen in large proportion of patients

The study comprised 655 adults diagnosed with type 2 diabetes for at least a year who received a prescription for a basal insulin (glargine U-100, glargine U-300, detemir, degludec U-100, degludec U-200, regular U-500, or NPH insulin).

The patients had a mean hemoglobin A1c of 8.4% and a mean basal insulin dose 0.4 units/kg per day. The prevalence of overbasalization was 38.1% for those with hemoglobin A1c above 8%, 42.7% for those with A1c of 9% or above, and 42% with A1c of 10% or greater.

Patient characteristics independently associated with overbasalization were age 35-54 years (odds ratio 1.89), age 65-80 years (0.44), A1c 9% or greater (13.97), and A1c 10% or greater (6.04). Having a prescription for insulin glargine U-100 was associated with a lower overbasalization risk (0.62). In multivariate analysis, only an A1c of 9% or greater remained significant.

Rozalina G. McCoy, MD, an endocrinologist and primary care clinician at the Mayo Clinic, Rochester, Minn., said in an interview that she sees [overbasalization] frequently in patients who are referred to her. “It’s kind of that wall that patients with type 2 diabetes hit because their A1c is high but their fasting blood sugars are normal. Sometimes it’s assumed that there’s a discrepancy, because people don’t always think about postprandial hyperglycemia.”

She also noted that there has been a push in recent years to simplify regimens, particularly in older patients.

“We really want to avoid rapid-acting insulin in older patients because we’re afraid of hypoglycemia, so we start them on basal and keep the noninsulins like metformin and sulfonylureas around. Initially those control the postprandial blood sugar but over time they’re no longer enough.”
 

Options exist for addressing postmeal blood sugar highs while minimizing lows

While in the past adding premeal insulin was the only option, today there are alternatives for addressing postmeal hyperglycemia, at least in the short term.

Dr. Cowart advised that the first step is to have patients self-monitor their blood glucose and titrate their basal insulin to address fasting hyperglycemia first. Once that appropriate dose is reached, if the patient’s hemoglobin A1c is still above target, the next step is to evaluate the need for postmeal control.

For patients who are at high cardiovascular risk, the next step might involve adding a sodium-glucose cotransporter 2 inhibitor (SGLT2i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA) instead of premeal insulin. But for patients in whom overbasalization is the main concern, a GLP-1RA might be the better choice since it will have a greater impact on postprandial glucose levels, while an SGLT2i will have more effect on fasting blood sugar, he said.

Another option is to use a fixed-dose combination of basal insulin and a glucagon-like peptide 1 receptor agonist (GLP-1RA), provided there aren’t cost or formulary barriers. “We want to use the right combination of drugs and not use too much of one to lead to hypoglycemia,” Dr. Cowart said.

Dr. McCoy doesn’t use fixed-dose combinations because they don’t allow as much flexibility in dosing. To correct overbasalization, she also recommends adding either a GLP-1RA or SGLT2i instead of premeal insulin. However, she cautions, “you still have to monitor those patients because after a few years it still won’t be enough and you’ll have to add mealtime insulin.”

If cost or lack of coverage prevents a patient’s use of SLGT2i/GLP-1RAs, Dr. McCoy said that adding just one premeal injection of rapid-acting insulin before the largest meal of the day is one option. Another is to use twice-daily NPH insulin instead of analog basal insulin, since that does offer some postprandial coverage.

Dr. Cowart said his approach in cost barrier situations is to try to use patient assistance programs and to look into the patient’s formulary to see if there is step therapy or tier considerations, and maybe have a discussion with the insurance company. “We often have to navigate that, and it does take a significant amount of time and could potentially delay patients getting the right therapy when it’s warranted. That is an area where there is a particular role for pharmacists in helping to overcome that and get patients on the right drugs,” he explained.
 

Problem may be even more common; testing is key

Dr. McCoy said that the A1c cutoff of 8% used to define overbasalization in the study probably resulted in an underestimation of the problem, since many patients are experiencing nighttime hypoglycemia from the basal insulin. The lows bring down their A1c level, but they’re still experiencing postmeal highs.

“I think they’re missing a lot of people, to be honest. I see a lot of patients with A1cs that aren’t that bad, say 7.5%, and their fasting blood sugars are okay, but if you were to put a [continuous glucose monitor] on those patients, invariably there’s hypoglycemia at night that no one knew about.”

Of course, for insurance reasons, most people with type 2 diabetes don’t currently have access to continuous glucose monitors. And often those who are not taking multiple daily injections are limited to one fingerstick test strip a day.

Dr. McCoy says that if hypoglycemia is a concern she will write a prior authorization justifying more test strips.

“I state explicitly in my notes why I recommend frequent monitoring. If they’re on a sulfonylurea, they should be able to check more frequently because they can have hypoglycemia. Same thing with basal insulin.”

Dr. McCoy advises that patients test their blood sugar 2 hours after the largest meal on one day, and at other times on different days. “Blood glucose after a meal shouldn’t be more than 200 [mg/dL]. If it is, that’s not a failure of basal insulin. It’s doing its job. You just need a different agent.”

Dr. Cowart has no disclosures. Dr. McCoy receives funding from the National Institutes of Health.

Overuse of basal insulin rather than adding therapies that target mealtime glucose levels is a common problem in primary care management of type 2 diabetes that impedes achievement of optimal glycemic control, new research suggests.

Such ‘overbasalization,’ defined as a hemoglobin A1c of greater than 8% despite use of more than 0.5 units/kg per day of basal insulin, was identified in about 40% of patients seen in a Florida primary care clinic during 2015-2018. The findings were published in the April 2021 issue of Clinical Diabetes by Kevin Cowart, PharmD, a diabetes care and education specialist at the University of South Florida, Tampa, and colleagues.

The literature suggests that once people with type 2 diabetes start basal insulin, the chance that they’ll achieve a given hemoglobin A1c target, i.e., less than 7%, diminishes significantly if that goal isn’t achieved within the first year of starting insulin, Dr. Cowart said in an interview.

“Our analysis suggests that overbasalization plays a role in patients with type 2 diabetes on basal insulin not achieving optimal glycemic control. Basal insulin is not designed to address postprandial hyperglycemia. I think there’s a clear need to address hesitancy in therapeutic progression beyond basal insulin. A lot of factors underlie the delays, with therapeutic inertia being one of them. It’s complex,” he said.
 

Overbasalization seen in large proportion of patients

The study comprised 655 adults diagnosed with type 2 diabetes for at least a year who received a prescription for a basal insulin (glargine U-100, glargine U-300, detemir, degludec U-100, degludec U-200, regular U-500, or NPH insulin).

The patients had a mean hemoglobin A1c of 8.4% and a mean basal insulin dose 0.4 units/kg per day. The prevalence of overbasalization was 38.1% for those with hemoglobin A1c above 8%, 42.7% for those with A1c of 9% or above, and 42% with A1c of 10% or greater.

Patient characteristics independently associated with overbasalization were age 35-54 years (odds ratio 1.89), age 65-80 years (0.44), A1c 9% or greater (13.97), and A1c 10% or greater (6.04). Having a prescription for insulin glargine U-100 was associated with a lower overbasalization risk (0.62). In multivariate analysis, only an A1c of 9% or greater remained significant.

Rozalina G. McCoy, MD, an endocrinologist and primary care clinician at the Mayo Clinic, Rochester, Minn., said in an interview that she sees [overbasalization] frequently in patients who are referred to her. “It’s kind of that wall that patients with type 2 diabetes hit because their A1c is high but their fasting blood sugars are normal. Sometimes it’s assumed that there’s a discrepancy, because people don’t always think about postprandial hyperglycemia.”

She also noted that there has been a push in recent years to simplify regimens, particularly in older patients.

“We really want to avoid rapid-acting insulin in older patients because we’re afraid of hypoglycemia, so we start them on basal and keep the noninsulins like metformin and sulfonylureas around. Initially those control the postprandial blood sugar but over time they’re no longer enough.”
 

Options exist for addressing postmeal blood sugar highs while minimizing lows

While in the past adding premeal insulin was the only option, today there are alternatives for addressing postmeal hyperglycemia, at least in the short term.

Dr. Cowart advised that the first step is to have patients self-monitor their blood glucose and titrate their basal insulin to address fasting hyperglycemia first. Once that appropriate dose is reached, if the patient’s hemoglobin A1c is still above target, the next step is to evaluate the need for postmeal control.

For patients who are at high cardiovascular risk, the next step might involve adding a sodium-glucose cotransporter 2 inhibitor (SGLT2i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA) instead of premeal insulin. But for patients in whom overbasalization is the main concern, a GLP-1RA might be the better choice since it will have a greater impact on postprandial glucose levels, while an SGLT2i will have more effect on fasting blood sugar, he said.

Another option is to use a fixed-dose combination of basal insulin and a glucagon-like peptide 1 receptor agonist (GLP-1RA), provided there aren’t cost or formulary barriers. “We want to use the right combination of drugs and not use too much of one to lead to hypoglycemia,” Dr. Cowart said.

Dr. McCoy doesn’t use fixed-dose combinations because they don’t allow as much flexibility in dosing. To correct overbasalization, she also recommends adding either a GLP-1RA or SGLT2i instead of premeal insulin. However, she cautions, “you still have to monitor those patients because after a few years it still won’t be enough and you’ll have to add mealtime insulin.”

If cost or lack of coverage prevents a patient’s use of SLGT2i/GLP-1RAs, Dr. McCoy said that adding just one premeal injection of rapid-acting insulin before the largest meal of the day is one option. Another is to use twice-daily NPH insulin instead of analog basal insulin, since that does offer some postprandial coverage.

Dr. Cowart said his approach in cost barrier situations is to try to use patient assistance programs and to look into the patient’s formulary to see if there is step therapy or tier considerations, and maybe have a discussion with the insurance company. “We often have to navigate that, and it does take a significant amount of time and could potentially delay patients getting the right therapy when it’s warranted. That is an area where there is a particular role for pharmacists in helping to overcome that and get patients on the right drugs,” he explained.
 

Problem may be even more common; testing is key

Dr. McCoy said that the A1c cutoff of 8% used to define overbasalization in the study probably resulted in an underestimation of the problem, since many patients are experiencing nighttime hypoglycemia from the basal insulin. The lows bring down their A1c level, but they’re still experiencing postmeal highs.

“I think they’re missing a lot of people, to be honest. I see a lot of patients with A1cs that aren’t that bad, say 7.5%, and their fasting blood sugars are okay, but if you were to put a [continuous glucose monitor] on those patients, invariably there’s hypoglycemia at night that no one knew about.”

Of course, for insurance reasons, most people with type 2 diabetes don’t currently have access to continuous glucose monitors. And often those who are not taking multiple daily injections are limited to one fingerstick test strip a day.

Dr. McCoy says that if hypoglycemia is a concern she will write a prior authorization justifying more test strips.

“I state explicitly in my notes why I recommend frequent monitoring. If they’re on a sulfonylurea, they should be able to check more frequently because they can have hypoglycemia. Same thing with basal insulin.”

Dr. McCoy advises that patients test their blood sugar 2 hours after the largest meal on one day, and at other times on different days. “Blood glucose after a meal shouldn’t be more than 200 [mg/dL]. If it is, that’s not a failure of basal insulin. It’s doing its job. You just need a different agent.”

Dr. Cowart has no disclosures. Dr. McCoy receives funding from the National Institutes of Health.

Mortality is two to three times higher in patients with adrenal incidentalomas who have autonomous cortisol secretion levels of 83 nmol/L (3 µg/dL) or more after a 1 mg dexamethasone suppression test (DST), compared with those with levels below this, new research finds.

Autonomous cortisol secretion (ACS) has been linked to hypertension, cardiovascular disease, type 2 diabetes, and early mortality, and risks vary by cortisol level.

“To adequately decide whether treatment should be surgery or medical management of possible complications, it is essential to know the risk associated with the actual level of ACS,” write Albin Kjellbom, MD, of Skåne University Hospital, Lund, Sweden, and colleagues, in their article published May 25 in Annals of Internal Medicine.

Asked to comment, Salila Kurra, MD, of the Columbia adrenal center, Columbia University, New York, told this news organization that “this idea that mild cortisol excess that doesn’t meet the threshold for overt Cushing’s can, in and of itself, cause increased morbidity and mortality is something people have been thinking about for many years now.”

“But there isn’t very clear guidance on exactly what to do in that situation, whether the incidentaloma should be removed, medically managed, or the patient should just be watched ... It may be clinically significant, but the way to sort that out is to do other testing.”   
 

Most deaths were from cardiovascular disease or cancer

Adrenal lesions are found incidentally in approximately 2% to 7% of the adult population who undergo abdominal imaging, and up to a third of those have ACS in the absence of clinical signs of Cushing syndrome.

European guidelines state that a plasma cortisol level of 138 nmol/L (5 µg/dL) or greater following DST defines ACS, and a level less than 50 nmol/L (1.8 µg/dL) rules it out, while values 50-137 (1.8-5 µg/dL) are deemed “possible” ACS.

For their study, the authors retrospectively analyzed 1,048 consecutive patients with adrenal incidentalomas seen at two Swedish hospitals between 2005 and September 2015 who were followed for up to 14 years.

The patients were a median age of 64.9 years, and 58.5% were women.

At baseline, 45.1% had a cortisol level of 50 nmol/L (1.8 µg/dL) or higher following DST, 52.9% had hypertension, 18.7% had diabetes, and 20.6% had a medical history of one or more cardiovascular events. A total of 54 patients underwent adrenalectomy, eight of them more than 2 years after the DST.

Researchers found a linear increase in mortality risk with increasing cortisol values up to 200 nmol/L (7.25 µg/dL) following DST.

Over 14 years, 16.2% (170 patients) died. Compared with cortisol less than 50 nmol/L (1.8 µg/dL) following DST, adjusted hazard ratios for mortality were 2.30 and 3.04 for cortisol levels 83 to 137 nmol/L (3-5 µg/dL) and 138 nmol/L (5 µg/dL) or greater, respectively, and both were significant.

Among the patients who died, causes of death were cardiovascular disease in 38%, cancer in 30%, infection in 4%, and other diseases in 28%.

Patients with post-DST cortisol levels of 83 nmol/L (3 µg/dL) or higher had increased cardiovascular mortality, while those with levels of 50-82 nmol/L (1.8-3.0 µg/dL) did not. In contrast, mortality rates from cancer, infection, and other diseases didn’t vary across groups.
 

Implications: Further testing, prospective studies needed

“The increase in mortality associated with cortisol DST values of 83 nmol/L or higher has implications,” the authors say.

“We suggest [medical] treatment of known cardiovascular risk factors in these patients and incorporation of our results in the decision about which patients to recommend for adrenalectomy.”

In contrast, ACS with lower cortisol (<83 nmol/L or 3 µg/dL) following DST “is not associated with clinically relevant increased mortality within 5 to 10 years,” they observe.

Dr. Kurra said she would perform further testing for any patient with an adrenal incidentaloma and a cortisol level 50-137 nmol/L (1.8-5 µg/dL) following DST: Specifically, a dehydroepiandrosterone sulfate (DHEAS) test.

“If DHEAS is low and the patient has metabolic complications, then I will work them up more, with adrenocorticotropin (ACTH) and 24-hour urine and go down that path of looking for the extent of overproduction of cortisol.”

She recommended an algorithm published in 2017 of an age- and sex-adjusted DHEAS ratio that provides a sensitive and specific screening test for subclinical hypercortisolism in patients with adrenal incidentalomas.

In further analyses by Dr. Kjellbom and colleagues into incidentaloma size, bilateralism, basal ACTH less than 2.0 pmol/L, or DHEAS less than 1.04 mmol/L, only DHEAS significantly predicted mortality.

“This should be studied further, specific to sex, age, and [post-DST]-cortisol strata,” Dr. Kjellbom and colleagues say.

In conclusion, Dr. Kurra said the new data “confirm something that people have postulated. But because it’s a retrospective review, we need prospective studies. It is an interesting finding that needs further study before we can change clinical practice.”

The study was funded by unrestricted grants from the Lisa and Johan Grönberg Foundation and the Gyllenstiernska Krapperup Foundation. Dr. Kjellbom and Dr. Kurra have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Mortality is two to three times higher in patients with adrenal incidentalomas who have autonomous cortisol secretion levels of 83 nmol/L (3 µg/dL) or more after a 1 mg dexamethasone suppression test (DST), compared with those with levels below this, new research finds.

Autonomous cortisol secretion (ACS) has been linked to hypertension, cardiovascular disease, type 2 diabetes, and early mortality, and risks vary by cortisol level.

“To adequately decide whether treatment should be surgery or medical management of possible complications, it is essential to know the risk associated with the actual level of ACS,” write Albin Kjellbom, MD, of Skåne University Hospital, Lund, Sweden, and colleagues, in their article published May 25 in Annals of Internal Medicine.

Asked to comment, Salila Kurra, MD, of the Columbia adrenal center, Columbia University, New York, told this news organization that “this idea that mild cortisol excess that doesn’t meet the threshold for overt Cushing’s can, in and of itself, cause increased morbidity and mortality is something people have been thinking about for many years now.”

“But there isn’t very clear guidance on exactly what to do in that situation, whether the incidentaloma should be removed, medically managed, or the patient should just be watched ... It may be clinically significant, but the way to sort that out is to do other testing.”   
 

Most deaths were from cardiovascular disease or cancer

Adrenal lesions are found incidentally in approximately 2% to 7% of the adult population who undergo abdominal imaging, and up to a third of those have ACS in the absence of clinical signs of Cushing syndrome.

European guidelines state that a plasma cortisol level of 138 nmol/L (5 µg/dL) or greater following DST defines ACS, and a level less than 50 nmol/L (1.8 µg/dL) rules it out, while values 50-137 (1.8-5 µg/dL) are deemed “possible” ACS.

For their study, the authors retrospectively analyzed 1,048 consecutive patients with adrenal incidentalomas seen at two Swedish hospitals between 2005 and September 2015 who were followed for up to 14 years.

The patients were a median age of 64.9 years, and 58.5% were women.

At baseline, 45.1% had a cortisol level of 50 nmol/L (1.8 µg/dL) or higher following DST, 52.9% had hypertension, 18.7% had diabetes, and 20.6% had a medical history of one or more cardiovascular events. A total of 54 patients underwent adrenalectomy, eight of them more than 2 years after the DST.

Researchers found a linear increase in mortality risk with increasing cortisol values up to 200 nmol/L (7.25 µg/dL) following DST.

Over 14 years, 16.2% (170 patients) died. Compared with cortisol less than 50 nmol/L (1.8 µg/dL) following DST, adjusted hazard ratios for mortality were 2.30 and 3.04 for cortisol levels 83 to 137 nmol/L (3-5 µg/dL) and 138 nmol/L (5 µg/dL) or greater, respectively, and both were significant.

Among the patients who died, causes of death were cardiovascular disease in 38%, cancer in 30%, infection in 4%, and other diseases in 28%.

Patients with post-DST cortisol levels of 83 nmol/L (3 µg/dL) or higher had increased cardiovascular mortality, while those with levels of 50-82 nmol/L (1.8-3.0 µg/dL) did not. In contrast, mortality rates from cancer, infection, and other diseases didn’t vary across groups.
 

Implications: Further testing, prospective studies needed

“The increase in mortality associated with cortisol DST values of 83 nmol/L or higher has implications,” the authors say.

“We suggest [medical] treatment of known cardiovascular risk factors in these patients and incorporation of our results in the decision about which patients to recommend for adrenalectomy.”

In contrast, ACS with lower cortisol (<83 nmol/L or 3 µg/dL) following DST “is not associated with clinically relevant increased mortality within 5 to 10 years,” they observe.

Dr. Kurra said she would perform further testing for any patient with an adrenal incidentaloma and a cortisol level 50-137 nmol/L (1.8-5 µg/dL) following DST: Specifically, a dehydroepiandrosterone sulfate (DHEAS) test.

“If DHEAS is low and the patient has metabolic complications, then I will work them up more, with adrenocorticotropin (ACTH) and 24-hour urine and go down that path of looking for the extent of overproduction of cortisol.”

She recommended an algorithm published in 2017 of an age- and sex-adjusted DHEAS ratio that provides a sensitive and specific screening test for subclinical hypercortisolism in patients with adrenal incidentalomas.

In further analyses by Dr. Kjellbom and colleagues into incidentaloma size, bilateralism, basal ACTH less than 2.0 pmol/L, or DHEAS less than 1.04 mmol/L, only DHEAS significantly predicted mortality.

“This should be studied further, specific to sex, age, and [post-DST]-cortisol strata,” Dr. Kjellbom and colleagues say.

In conclusion, Dr. Kurra said the new data “confirm something that people have postulated. But because it’s a retrospective review, we need prospective studies. It is an interesting finding that needs further study before we can change clinical practice.”

The study was funded by unrestricted grants from the Lisa and Johan Grönberg Foundation and the Gyllenstiernska Krapperup Foundation. Dr. Kjellbom and Dr. Kurra have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Mortality is two to three times higher in patients with adrenal incidentalomas who have autonomous cortisol secretion levels of 83 nmol/L (3 µg/dL) or more after a 1 mg dexamethasone suppression test (DST), compared with those with levels below this, new research finds.

Autonomous cortisol secretion (ACS) has been linked to hypertension, cardiovascular disease, type 2 diabetes, and early mortality, and risks vary by cortisol level.

“To adequately decide whether treatment should be surgery or medical management of possible complications, it is essential to know the risk associated with the actual level of ACS,” write Albin Kjellbom, MD, of Skåne University Hospital, Lund, Sweden, and colleagues, in their article published May 25 in Annals of Internal Medicine.

Asked to comment, Salila Kurra, MD, of the Columbia adrenal center, Columbia University, New York, told this news organization that “this idea that mild cortisol excess that doesn’t meet the threshold for overt Cushing’s can, in and of itself, cause increased morbidity and mortality is something people have been thinking about for many years now.”

“But there isn’t very clear guidance on exactly what to do in that situation, whether the incidentaloma should be removed, medically managed, or the patient should just be watched ... It may be clinically significant, but the way to sort that out is to do other testing.”   
 

Most deaths were from cardiovascular disease or cancer

Adrenal lesions are found incidentally in approximately 2% to 7% of the adult population who undergo abdominal imaging, and up to a third of those have ACS in the absence of clinical signs of Cushing syndrome.

European guidelines state that a plasma cortisol level of 138 nmol/L (5 µg/dL) or greater following DST defines ACS, and a level less than 50 nmol/L (1.8 µg/dL) rules it out, while values 50-137 (1.8-5 µg/dL) are deemed “possible” ACS.

For their study, the authors retrospectively analyzed 1,048 consecutive patients with adrenal incidentalomas seen at two Swedish hospitals between 2005 and September 2015 who were followed for up to 14 years.

The patients were a median age of 64.9 years, and 58.5% were women.

At baseline, 45.1% had a cortisol level of 50 nmol/L (1.8 µg/dL) or higher following DST, 52.9% had hypertension, 18.7% had diabetes, and 20.6% had a medical history of one or more cardiovascular events. A total of 54 patients underwent adrenalectomy, eight of them more than 2 years after the DST.

Researchers found a linear increase in mortality risk with increasing cortisol values up to 200 nmol/L (7.25 µg/dL) following DST.

Over 14 years, 16.2% (170 patients) died. Compared with cortisol less than 50 nmol/L (1.8 µg/dL) following DST, adjusted hazard ratios for mortality were 2.30 and 3.04 for cortisol levels 83 to 137 nmol/L (3-5 µg/dL) and 138 nmol/L (5 µg/dL) or greater, respectively, and both were significant.

Among the patients who died, causes of death were cardiovascular disease in 38%, cancer in 30%, infection in 4%, and other diseases in 28%.

Patients with post-DST cortisol levels of 83 nmol/L (3 µg/dL) or higher had increased cardiovascular mortality, while those with levels of 50-82 nmol/L (1.8-3.0 µg/dL) did not. In contrast, mortality rates from cancer, infection, and other diseases didn’t vary across groups.
 

Implications: Further testing, prospective studies needed

“The increase in mortality associated with cortisol DST values of 83 nmol/L or higher has implications,” the authors say.

“We suggest [medical] treatment of known cardiovascular risk factors in these patients and incorporation of our results in the decision about which patients to recommend for adrenalectomy.”

In contrast, ACS with lower cortisol (<83 nmol/L or 3 µg/dL) following DST “is not associated with clinically relevant increased mortality within 5 to 10 years,” they observe.

Dr. Kurra said she would perform further testing for any patient with an adrenal incidentaloma and a cortisol level 50-137 nmol/L (1.8-5 µg/dL) following DST: Specifically, a dehydroepiandrosterone sulfate (DHEAS) test.

“If DHEAS is low and the patient has metabolic complications, then I will work them up more, with adrenocorticotropin (ACTH) and 24-hour urine and go down that path of looking for the extent of overproduction of cortisol.”

She recommended an algorithm published in 2017 of an age- and sex-adjusted DHEAS ratio that provides a sensitive and specific screening test for subclinical hypercortisolism in patients with adrenal incidentalomas.

In further analyses by Dr. Kjellbom and colleagues into incidentaloma size, bilateralism, basal ACTH less than 2.0 pmol/L, or DHEAS less than 1.04 mmol/L, only DHEAS significantly predicted mortality.

“This should be studied further, specific to sex, age, and [post-DST]-cortisol strata,” Dr. Kjellbom and colleagues say.

In conclusion, Dr. Kurra said the new data “confirm something that people have postulated. But because it’s a retrospective review, we need prospective studies. It is an interesting finding that needs further study before we can change clinical practice.”

The study was funded by unrestricted grants from the Lisa and Johan Grönberg Foundation and the Gyllenstiernska Krapperup Foundation. Dr. Kjellbom and Dr. Kurra have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A peripherally-acting substance that boosts energy expenditure and reduces fat mass has the potential to become an obesity treatment that doesn’t produce cardiovascular or psychiatric side effects, scientists say.

The agent, BIBO3304, is a selective antagonist of the neuropeptide Y1 receptor, which is elevated in the fat tissue of individuals with obesity, resulting in reduced fat accumulation. It was originally developed more than 25 years ago by scientists at Boehringer Ingelheim, who had thought that it would reduce appetite by targeting Y1 receptors in the brain. But when it didn’t cross the blood-brain barrier as an oral drug, the company abandoned it.

Now a series of experiments by Chenxu Yan, of the Garvan Institute of Medical Research, St. Vincent’s Hospital, Sydney, and colleagues have shown that “BIBO” works directly on Y1 receptors in the periphery to turn fat-storing white fat cells into heat-generating brown-like fat tissue, thereby enhancing energy expenditure.

The data were published online May 11 in Nature Communications.
 

Drug’s lack of effect on the brain turns out to be a positive

“Rather than just having the cells store fat, we change their characteristics so that most of the excess energy gets burned and produces heat instead of being stored as fat. BIBO programs the cell toward a more heat-producing cell rather than a fat-storing cell,” study coauthor Herbert Herzog, PhD, of the Garvan Institute, said in an interview.

Importantly, he said, the lack of effect on the brain that caused the drug’s initial developer to abandon it turns out to be a positive.

“As we looked at fat specifically, and we didn’t want to have any interference with the brain, this seems to work out as a real advantage … It has the desired effect of blocking fat accumulation but has the enormous benefit of not interfering with any brain function. That’s why so many of the obesity drugs that were on the market were taken off, because of the side effects they caused in the brain on mood and cardiovascular control. It’s a completely different ball game.”

The problem now, he said, is that because BIBO is off-patent, no pharmaceutical company is currently willing to invest in its development as a peripherally acting weight-loss drug, despite its potential advantages.

“We’re trying to find some interested party to help us get this to the clinical setting. We’re basic scientists. We need big money. We can do small-scale studies to get proof of principle. Hopefully, if that’s interesting, some bigger company will come along,” said Dr. Herzog.
 

Experiments in mice, human tissues demonstrate principle

In the series of studies, investigators fed genetically inbred mice a high-fat, high-sugar diet while giving BIBO to half of them. Over 8 weeks, the mice given BIBO had 40% less gain in fat mass compared to those overfed without the drug, despite them all eating the same amount.

Using a noninvasive infrared camera to measure skin surface temperature above brown adipose tissue, they found that the temperature was significantly increased with BIBO, independent of the weight of the brown fat.

This suggests that the thermogenesis of the brown fat is significantly contributing to whole-body energy expenditure. “With the drug, the mice have far greater energy expenditure measured by heat production,” Dr. Herzog explained.

In vitro experiments showed that Y1R blockade by BIBO induced “beigeing” of white fat deposits into more heat-producing brown fat. The body temperature increase is about 0.1-0.2ºC. “That’s a tiny amount, but it actually requires quite a lot of energy,” he said.

Experiments using fat tissue taken from obese and normal-weight humans showed the same thermogenesis with BIBO. “It’s such a fundamental process [that] you wouldn’t expect it to differ. The same mechanism is even found in flies and primitive worms,” he noted.
 

Neuropeptide Y receptor blockage: A treatment for many ills?

Previously, Dr. Herzog and colleagues found that blockade of the neuropeptide Y1 receptor also increases bone mass in mice.

“It’s a modest effect, but there’s nothing out there at the moment that really improves bone mass. If you can stop osteoporosis, that’s a benefit on its own,” he said.

Now they hope to study BIBO’s vasodilatory properties as a potential treatment for hypertension, if they get the funding.

Dr. Herzog is hopeful, as obesity, osteoporosis, and hypertension are all chronic conditions. “Having one drug that benefits them all would surely be of interest to clinicians and drug companies,” he observed.  

Dr. Yan and Dr. Herzog have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A peripherally-acting substance that boosts energy expenditure and reduces fat mass has the potential to become an obesity treatment that doesn’t produce cardiovascular or psychiatric side effects, scientists say.

The agent, BIBO3304, is a selective antagonist of the neuropeptide Y1 receptor, which is elevated in the fat tissue of individuals with obesity, resulting in reduced fat accumulation. It was originally developed more than 25 years ago by scientists at Boehringer Ingelheim, who had thought that it would reduce appetite by targeting Y1 receptors in the brain. But when it didn’t cross the blood-brain barrier as an oral drug, the company abandoned it.

Now a series of experiments by Chenxu Yan, of the Garvan Institute of Medical Research, St. Vincent’s Hospital, Sydney, and colleagues have shown that “BIBO” works directly on Y1 receptors in the periphery to turn fat-storing white fat cells into heat-generating brown-like fat tissue, thereby enhancing energy expenditure.

The data were published online May 11 in Nature Communications.
 

Drug’s lack of effect on the brain turns out to be a positive

“Rather than just having the cells store fat, we change their characteristics so that most of the excess energy gets burned and produces heat instead of being stored as fat. BIBO programs the cell toward a more heat-producing cell rather than a fat-storing cell,” study coauthor Herbert Herzog, PhD, of the Garvan Institute, said in an interview.

Importantly, he said, the lack of effect on the brain that caused the drug’s initial developer to abandon it turns out to be a positive.

“As we looked at fat specifically, and we didn’t want to have any interference with the brain, this seems to work out as a real advantage … It has the desired effect of blocking fat accumulation but has the enormous benefit of not interfering with any brain function. That’s why so many of the obesity drugs that were on the market were taken off, because of the side effects they caused in the brain on mood and cardiovascular control. It’s a completely different ball game.”

The problem now, he said, is that because BIBO is off-patent, no pharmaceutical company is currently willing to invest in its development as a peripherally acting weight-loss drug, despite its potential advantages.

“We’re trying to find some interested party to help us get this to the clinical setting. We’re basic scientists. We need big money. We can do small-scale studies to get proof of principle. Hopefully, if that’s interesting, some bigger company will come along,” said Dr. Herzog.
 

Experiments in mice, human tissues demonstrate principle

In the series of studies, investigators fed genetically inbred mice a high-fat, high-sugar diet while giving BIBO to half of them. Over 8 weeks, the mice given BIBO had 40% less gain in fat mass compared to those overfed without the drug, despite them all eating the same amount.

Using a noninvasive infrared camera to measure skin surface temperature above brown adipose tissue, they found that the temperature was significantly increased with BIBO, independent of the weight of the brown fat.

This suggests that the thermogenesis of the brown fat is significantly contributing to whole-body energy expenditure. “With the drug, the mice have far greater energy expenditure measured by heat production,” Dr. Herzog explained.

In vitro experiments showed that Y1R blockade by BIBO induced “beigeing” of white fat deposits into more heat-producing brown fat. The body temperature increase is about 0.1-0.2ºC. “That’s a tiny amount, but it actually requires quite a lot of energy,” he said.

Experiments using fat tissue taken from obese and normal-weight humans showed the same thermogenesis with BIBO. “It’s such a fundamental process [that] you wouldn’t expect it to differ. The same mechanism is even found in flies and primitive worms,” he noted.
 

Neuropeptide Y receptor blockage: A treatment for many ills?

Previously, Dr. Herzog and colleagues found that blockade of the neuropeptide Y1 receptor also increases bone mass in mice.

“It’s a modest effect, but there’s nothing out there at the moment that really improves bone mass. If you can stop osteoporosis, that’s a benefit on its own,” he said.

Now they hope to study BIBO’s vasodilatory properties as a potential treatment for hypertension, if they get the funding.

Dr. Herzog is hopeful, as obesity, osteoporosis, and hypertension are all chronic conditions. “Having one drug that benefits them all would surely be of interest to clinicians and drug companies,” he observed.  

Dr. Yan and Dr. Herzog have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A peripherally-acting substance that boosts energy expenditure and reduces fat mass has the potential to become an obesity treatment that doesn’t produce cardiovascular or psychiatric side effects, scientists say.

The agent, BIBO3304, is a selective antagonist of the neuropeptide Y1 receptor, which is elevated in the fat tissue of individuals with obesity, resulting in reduced fat accumulation. It was originally developed more than 25 years ago by scientists at Boehringer Ingelheim, who had thought that it would reduce appetite by targeting Y1 receptors in the brain. But when it didn’t cross the blood-brain barrier as an oral drug, the company abandoned it.

Now a series of experiments by Chenxu Yan, of the Garvan Institute of Medical Research, St. Vincent’s Hospital, Sydney, and colleagues have shown that “BIBO” works directly on Y1 receptors in the periphery to turn fat-storing white fat cells into heat-generating brown-like fat tissue, thereby enhancing energy expenditure.

The data were published online May 11 in Nature Communications.
 

Drug’s lack of effect on the brain turns out to be a positive

“Rather than just having the cells store fat, we change their characteristics so that most of the excess energy gets burned and produces heat instead of being stored as fat. BIBO programs the cell toward a more heat-producing cell rather than a fat-storing cell,” study coauthor Herbert Herzog, PhD, of the Garvan Institute, said in an interview.

Importantly, he said, the lack of effect on the brain that caused the drug’s initial developer to abandon it turns out to be a positive.

“As we looked at fat specifically, and we didn’t want to have any interference with the brain, this seems to work out as a real advantage … It has the desired effect of blocking fat accumulation but has the enormous benefit of not interfering with any brain function. That’s why so many of the obesity drugs that were on the market were taken off, because of the side effects they caused in the brain on mood and cardiovascular control. It’s a completely different ball game.”

The problem now, he said, is that because BIBO is off-patent, no pharmaceutical company is currently willing to invest in its development as a peripherally acting weight-loss drug, despite its potential advantages.

“We’re trying to find some interested party to help us get this to the clinical setting. We’re basic scientists. We need big money. We can do small-scale studies to get proof of principle. Hopefully, if that’s interesting, some bigger company will come along,” said Dr. Herzog.
 

Experiments in mice, human tissues demonstrate principle

In the series of studies, investigators fed genetically inbred mice a high-fat, high-sugar diet while giving BIBO to half of them. Over 8 weeks, the mice given BIBO had 40% less gain in fat mass compared to those overfed without the drug, despite them all eating the same amount.

Using a noninvasive infrared camera to measure skin surface temperature above brown adipose tissue, they found that the temperature was significantly increased with BIBO, independent of the weight of the brown fat.

This suggests that the thermogenesis of the brown fat is significantly contributing to whole-body energy expenditure. “With the drug, the mice have far greater energy expenditure measured by heat production,” Dr. Herzog explained.

In vitro experiments showed that Y1R blockade by BIBO induced “beigeing” of white fat deposits into more heat-producing brown fat. The body temperature increase is about 0.1-0.2ºC. “That’s a tiny amount, but it actually requires quite a lot of energy,” he said.

Experiments using fat tissue taken from obese and normal-weight humans showed the same thermogenesis with BIBO. “It’s such a fundamental process [that] you wouldn’t expect it to differ. The same mechanism is even found in flies and primitive worms,” he noted.
 

Neuropeptide Y receptor blockage: A treatment for many ills?

Previously, Dr. Herzog and colleagues found that blockade of the neuropeptide Y1 receptor also increases bone mass in mice.

“It’s a modest effect, but there’s nothing out there at the moment that really improves bone mass. If you can stop osteoporosis, that’s a benefit on its own,” he said.

Now they hope to study BIBO’s vasodilatory properties as a potential treatment for hypertension, if they get the funding.

Dr. Herzog is hopeful, as obesity, osteoporosis, and hypertension are all chronic conditions. “Having one drug that benefits them all would surely be of interest to clinicians and drug companies,” he observed.  

Dr. Yan and Dr. Herzog have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has cleared the Bigfoot Unity Diabetes Management System, a cap device that connects to insulin pens and translates continuous glucose data into dosing recommendations, for use in individuals aged 12 and older.

The Bigfoot Unity System has three primary components – proprietary smart pen caps for both rapid- and long-acting insulin, a mobile app, and an integrated FreeStyle Libre 2 continuous glucose monitor (iCGM) sensor, which was FDA-cleared in June 2020 – that fit into the person’s dose-decision process when they need it throughout the day.

It allows the user to scan the FreeStyle Libre 2 sensor, displaying the user’s current glucose value, trend arrow, and recommended correction dose. The smart pen cap also directly displays the health care provider’s suggested meal insulin doses with the correction dose. In just a few steps the system gives the person with diabetes support to make real-time treatment decisions.

It also includes hypoglycemia alerts and is compatible with all major U.S. brands of rapid- and long-acting disposable insulin pens.  

Health care providers can monitor the patient’s data through a secure web portal called the Bigfoot Clinic Hub.

JDRF said in a statement it “applauds the U.S. FDA on its decision to provide clearance for the Bigfoot Unity Diabetes Management by Bigfoot Biomedical.”

The new system “fills a critical gap and brings benefits of automation and device interconnectedness to people with diabetes who rely on multiple daily injections to manage their blood sugar levels.” It is a “win for both the type 1 and type 2 diabetes communities as it broadens the options of treatment to alleviate daily burdens.”
 

Growing market for smart insulin pens

The device is the latest advance in the “smart pen” field of semiautomated insulin delivery in which pen and compatible devices, software, and platforms are teamed up in various combinations to provide easier insulin dosing for patients with diabetes who require multiple daily injections but don’t wear insulin pumps.

On May 6, 2021, Eli Lilly announced it had signed “strategic international agreements” with Dexcom, Glooko, MyDiabby Healthcare, and Roche to provide platforms or devices compatible with Lilly’s prefilled Tempo Pen, which is already available in several global markets, and the Tempo Smart Button, currently in late-stage development and pending CE mark.  

And in November 2020, Medtronic launched a new version of its smart insulin pen with integrated CGM called the InPen. The reusable insulin injector pen uses a smartphone app to calculate dosing of short-acting insulin based on CGM readings and allows users to view glucose readings and insulin dose information. It was originally launched in 2017 by Companion Medical, and the company was acquired by Medtronic in September 2020.

Novo Nordisk and Sanofi are also developing products in the smart pen space.

More information about the Bigfoot Unity Program is available here.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has cleared the Bigfoot Unity Diabetes Management System, a cap device that connects to insulin pens and translates continuous glucose data into dosing recommendations, for use in individuals aged 12 and older.

The Bigfoot Unity System has three primary components – proprietary smart pen caps for both rapid- and long-acting insulin, a mobile app, and an integrated FreeStyle Libre 2 continuous glucose monitor (iCGM) sensor, which was FDA-cleared in June 2020 – that fit into the person’s dose-decision process when they need it throughout the day.

It allows the user to scan the FreeStyle Libre 2 sensor, displaying the user’s current glucose value, trend arrow, and recommended correction dose. The smart pen cap also directly displays the health care provider’s suggested meal insulin doses with the correction dose. In just a few steps the system gives the person with diabetes support to make real-time treatment decisions.

It also includes hypoglycemia alerts and is compatible with all major U.S. brands of rapid- and long-acting disposable insulin pens.  

Health care providers can monitor the patient’s data through a secure web portal called the Bigfoot Clinic Hub.

JDRF said in a statement it “applauds the U.S. FDA on its decision to provide clearance for the Bigfoot Unity Diabetes Management by Bigfoot Biomedical.”

The new system “fills a critical gap and brings benefits of automation and device interconnectedness to people with diabetes who rely on multiple daily injections to manage their blood sugar levels.” It is a “win for both the type 1 and type 2 diabetes communities as it broadens the options of treatment to alleviate daily burdens.”
 

Growing market for smart insulin pens

The device is the latest advance in the “smart pen” field of semiautomated insulin delivery in which pen and compatible devices, software, and platforms are teamed up in various combinations to provide easier insulin dosing for patients with diabetes who require multiple daily injections but don’t wear insulin pumps.

On May 6, 2021, Eli Lilly announced it had signed “strategic international agreements” with Dexcom, Glooko, MyDiabby Healthcare, and Roche to provide platforms or devices compatible with Lilly’s prefilled Tempo Pen, which is already available in several global markets, and the Tempo Smart Button, currently in late-stage development and pending CE mark.  

And in November 2020, Medtronic launched a new version of its smart insulin pen with integrated CGM called the InPen. The reusable insulin injector pen uses a smartphone app to calculate dosing of short-acting insulin based on CGM readings and allows users to view glucose readings and insulin dose information. It was originally launched in 2017 by Companion Medical, and the company was acquired by Medtronic in September 2020.

Novo Nordisk and Sanofi are also developing products in the smart pen space.

More information about the Bigfoot Unity Program is available here.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has cleared the Bigfoot Unity Diabetes Management System, a cap device that connects to insulin pens and translates continuous glucose data into dosing recommendations, for use in individuals aged 12 and older.

The Bigfoot Unity System has three primary components – proprietary smart pen caps for both rapid- and long-acting insulin, a mobile app, and an integrated FreeStyle Libre 2 continuous glucose monitor (iCGM) sensor, which was FDA-cleared in June 2020 – that fit into the person’s dose-decision process when they need it throughout the day.

It allows the user to scan the FreeStyle Libre 2 sensor, displaying the user’s current glucose value, trend arrow, and recommended correction dose. The smart pen cap also directly displays the health care provider’s suggested meal insulin doses with the correction dose. In just a few steps the system gives the person with diabetes support to make real-time treatment decisions.

It also includes hypoglycemia alerts and is compatible with all major U.S. brands of rapid- and long-acting disposable insulin pens.  

Health care providers can monitor the patient’s data through a secure web portal called the Bigfoot Clinic Hub.

JDRF said in a statement it “applauds the U.S. FDA on its decision to provide clearance for the Bigfoot Unity Diabetes Management by Bigfoot Biomedical.”

The new system “fills a critical gap and brings benefits of automation and device interconnectedness to people with diabetes who rely on multiple daily injections to manage their blood sugar levels.” It is a “win for both the type 1 and type 2 diabetes communities as it broadens the options of treatment to alleviate daily burdens.”
 

Growing market for smart insulin pens

The device is the latest advance in the “smart pen” field of semiautomated insulin delivery in which pen and compatible devices, software, and platforms are teamed up in various combinations to provide easier insulin dosing for patients with diabetes who require multiple daily injections but don’t wear insulin pumps.

On May 6, 2021, Eli Lilly announced it had signed “strategic international agreements” with Dexcom, Glooko, MyDiabby Healthcare, and Roche to provide platforms or devices compatible with Lilly’s prefilled Tempo Pen, which is already available in several global markets, and the Tempo Smart Button, currently in late-stage development and pending CE mark.  

And in November 2020, Medtronic launched a new version of its smart insulin pen with integrated CGM called the InPen. The reusable insulin injector pen uses a smartphone app to calculate dosing of short-acting insulin based on CGM readings and allows users to view glucose readings and insulin dose information. It was originally launched in 2017 by Companion Medical, and the company was acquired by Medtronic in September 2020.

Novo Nordisk and Sanofi are also developing products in the smart pen space.

More information about the Bigfoot Unity Program is available here.

A version of this article first appeared on Medscape.com.

Initiatives targeting hypoglycemia and insulin pen wastage could lead to dramatic cost savings in small community hospitals, new data suggest.

The two projects are part of a dedicated inpatient glucose management service led by Mihail (“Misha”) Zilbermint, MD, one of the few full-time endocrine hospitalists in the United States and one of even fewer who work at a small community hospital.

In 2019, Dr. Zilbermint and colleagues reported that their inpatient glucose management program resulted in a 27% reduction in length of stay and a 10.7% lower 30-day readmission rate. The projected cost savings for the period January 2016 to May 2017 was $953,578.

Dr. Zilbermint’s team has written two new articles that document cost savings for specific elements of the program; namely, a set of hospital-wide hypoglycemia prevention measures, and an initiative that reduced duplicate inpatient insulin pen dispensing.

About 1 in 4 people in U.S. hospitals have diabetes or hyperglycemia. Large academic hospitals have endocrine divisions and training programs, but 85% of people receive care at small community hospitals.

“There are management guidelines, but they’re not always followed ... That’s why I’ve been advocating for endocrine hospitalists to be deployed nationally,” Dr. Zilbermint said. He is chief and director of endocrinology, diabetes, and metabolism at Johns Hopkins Community Physicians at Suburban Hospital, Bethesda, Maryland.

Asked to comment on behalf of the Society of Hospital Medicine (SHM), Greg Maynard, MD, program lead for SHM’s Electronic Quality Improvement Programs, said that Suburban’s overall program goals align with those of the SHM.

“Dedicated inpatient glycemic control teams are very important and desirable to improve the quality and safety of care for inpatients with hyperglycemia and diabetes,” he said.

Regarding specific initiatives, such as those aimed at reducing hypoglycemia and insulin pen wastage, Dr. Maynard said, “All of these are feasible in a wide variety of institutions. The main barrier is getting the institutional support for people to work on these interventions. This series of studies can help spread the word about the positive return on investment.”

Another barrier – the current lack of publicly reported measures or pay-for-performance programs for hypoglycemia prevention and glycemic control – may soon change, added Dr. Maynard, who is also chief quality officer at the University of California, Davis, Medical Center.

“The National Quality Forum has endorsed new measures, and the CDC’s National Healthcare Safety Network is working on ways to augment those measures and embed them into their infrastructure,” he said.

Although SHM doesn’t specifically endorse full-time glycemic control hospitalists over endocrinology-trained glycemic control experts, “certainly hospitalists who accrue added training are very well positioned to be an important part of these interdisciplinary teams,” Dr. Maynard said.
 

‘The nurses were so afraid of hypoglycemia’

Tackling hypoglycemia was Dr. Zilbermint’s first priority when he started the glycemic management program at Suburban in late 2015.

“One of the most common complaints from the nurses was that a lot of their patients had hypoglycemia, especially in the ICU, when patients were placed on insulin infusion protocols ... Every time, the nurse would have to call the attending and ask what to do,” he explains.

In addition, Dr. Zilbermint says, there was no standard for treating hypoglycemia. A nurse in one unit would give two cups of juice, another a 50% dextrose infusion, or another, milk. Even more concerning, “the nurses were so afraid of hypoglycemia they would reflexively discontinue all insulin, including basal.”

So one of the new initiatives, led by Carter Shelton, MSHCM, an administrative fellow at the Medical University of South Carolina, Charleston, was to implement a set of hospital-wide hypoglycemia prevention measures, as described in an article published online April 21 in the Journal of Diabetes Science and Technology.
 

Inpatient hypoglycemia rate was cut nearly in half

This began in 2016, when the multidisciplinary Suburban Hospital Glucose Steering Committee identified four main causes of insulin-induced hypoglycemia (defined as a blood glucose level of ≤70 mg/dL in a patient who had received at least one dose of insulin in the past 24 hours) and devised solutions for each:

1. Lack of a unified hypoglycemia protocol. A formal, evidence-based, nurse-driven treatment protocol with clinical decision support in the electronic medical record was developed. The Suburban team adapted much of the protocol from one that had been recently implemented at the flagship Johns Hopkins Hospital, in Baltimore, Maryland.

According to that protocol, if patients are able to swallow, they are given 15 g or 30 g of carbohydrates in order to achieve a blood glucose level of 50 to 70 mg/dL and <50 mg/dL, respectively. Levels are checked 15 minutes later. Intravenous D50 or glucagon is reserved for patients who can’t swallow.

2. For patients in critical care, the insulin infusion protocol that had been in use set blood glucose targets of 80 to 110 mg/dL, which resulted in hypoglycemia in nearly every patient who received an insulin infusion. This protocol was changed to the currently recommended 140 to 180 mg/dL.

3. Most patients were managed with sliding-scale insulin, an outdated yet still widely used regimen whereby insulin is given based only on current blood glucose without accounting for carbohydrates consumed with meals and not corrected until the subsequent meal. This was changed so that nurses give insulin after the patient has consumed at least 50% of their meal carbohydrates.

4. Lack of hypoglycemia reporting. A glucometrics dashboard – now used throughout the Johns Hopkins system – was adopted to produce daily hypoglycemia reports in the EMR system that could be reviewed by the inpatient glucose management service to track quality metrics and plan further interventions.

Between Jan. 1, 2016, and Sept. 30, 2019, out of a total 49,315 patient-days, there were 2,682 days on which any hypoglycemia occurred and 874 days on which moderate hypoglycemia occurred (≤54 mg/dL). Type 2 diabetes accounted for 84.4% of the total patient-days; type 1 accounted for 4.4%.

The overall frequency of any hypoglycemia patient-days per month decreased from 7.5% to 3.9% during the study period (P = .001). This was significant for the patients with type 2 diabetes (7.4% to 3.8%; P < .0001) but not for those with type 1 diabetes (18.5% to 18.0%; P = .08).

Rates of moderate hypoglycemia also decreased significantly among the patients with type 2 diabetes (1.9% to 1.0%; P = .03) but not for those with type 1 diabetes (7.4% to 6.0%; P = .14).

On the basis of these rates in reducing hypoglycemia, in which the inpatient hypoglycemia rate was cut nearly in half, the estimated savings in cost of care to the hospital was $98,635 during the period of January 2016 to September 2019.
 

Reducing insulin pen waste by minimizing duplicate prescriptions

Suburban Hospital had been using insulin vials and syringes when Dr. Zilbermint first arrived there. He lobbied the administration to allow use of pens, because they’re easier to use and they reduce the risk for needlestick injuries. Nurses were educated and retrained monthly in their use.

The switch to pens – aspart (Novolog Flexpen) for bolus insulin and glargine (Lantus SoloSTAR) – took place in 2018. The cost of the aspart pen was $16.19, and the cost of glargine was $25.08. Each holds 300 units of insulin.

After the first month, the team noticed a large increase in expenses. A quality improvement project was devised to address the issue.

“We were dispensing sometimes three or four pens per person. That’s a lot. Each pen holds 300 units, so one pen should last the entire hospital stay of an average 4- or 5-day stay,” Dr. Zilbermint explained. “We had to figure out where we were bleeding the money and where the pens were going.”

When pens disappeared, the pharmacy would have to dispense new ones. One problem was that when patients were transferred from one unit to another, the pen would be left behind and the room would be cleaned. Sometimes the pens weren’t stored properly or were misplaced. Often, they’d end up in a nurse’s pocket.

The second intervention was led by Urooj Najmi, MD, of the American International School of Medicine, Atlanta, Georgia. A program was instituted to reduce duplicate inpatient insulin pen dispensing, as detailed in an article published in the same issue of the Journal of Diabetes Science and Technology.

Solutions to reduce duplicate pen dispensing included having pharmacy track daily insulin pen reports and monitor duplicate orders, with “do not dispense” instructions conveyed via the EMR system. All multidose medications, including insulin pens, were to be placed in patients’ bins at the nursing station, and nurses were instructed to look for patients’ insulin pens prior to their being transferred to another unit, rather than ask for a replacement pen.

From July 2018 to July 2019, 3,121 patients received insulin, of whom 95% received aspart and 47% received glargine. Of the 9,516 pens dispensed, 68% were for aspart and 32% were for glargine. During the study period, the number of pens dispensed per patient dropped from 2.2 to 1.2 for aspart and from 2.1 to 1.3 for glargine; differences were highly significant (P = .0002 and P = .0005, respectively).

The total amount of unnecessary dispensing during the first 4 months after initiating the pen implementation program was 58%. The average monthly cost was $11,820.68; the projected cost per year was $141,848.

Six months after the waste reduction strategies were implemented, monthly waste had dropped to 42%, translating to an estimated potential cost savings of $66,261 over 12 months.

Because Suburban Hospital doesn’t have an outpatient dispensing license, there is still wastage when patients are discharged, because they can’t take their pens home with them. That remains a challenge, Dr. Zilbermint noted.

The team is working on implementing automatic A1c testing for patients admitted with hyperglycemia who either have a history of diabetes or whose blood glucose level is >140 mg/dL. Dr. Zilbermint said, “it’s in the guidelines, but it’s not always done.”

Dr. Zilbermint is a consultant for Guidepoint. Dr. Maynard, Mr. Shelton, and Dr. Najmi have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Initiatives targeting hypoglycemia and insulin pen wastage could lead to dramatic cost savings in small community hospitals, new data suggest.

The two projects are part of a dedicated inpatient glucose management service led by Mihail (“Misha”) Zilbermint, MD, one of the few full-time endocrine hospitalists in the United States and one of even fewer who work at a small community hospital.

In 2019, Dr. Zilbermint and colleagues reported that their inpatient glucose management program resulted in a 27% reduction in length of stay and a 10.7% lower 30-day readmission rate. The projected cost savings for the period January 2016 to May 2017 was $953,578.

Dr. Zilbermint’s team has written two new articles that document cost savings for specific elements of the program; namely, a set of hospital-wide hypoglycemia prevention measures, and an initiative that reduced duplicate inpatient insulin pen dispensing.

About 1 in 4 people in U.S. hospitals have diabetes or hyperglycemia. Large academic hospitals have endocrine divisions and training programs, but 85% of people receive care at small community hospitals.

“There are management guidelines, but they’re not always followed ... That’s why I’ve been advocating for endocrine hospitalists to be deployed nationally,” Dr. Zilbermint said. He is chief and director of endocrinology, diabetes, and metabolism at Johns Hopkins Community Physicians at Suburban Hospital, Bethesda, Maryland.

Asked to comment on behalf of the Society of Hospital Medicine (SHM), Greg Maynard, MD, program lead for SHM’s Electronic Quality Improvement Programs, said that Suburban’s overall program goals align with those of the SHM.

“Dedicated inpatient glycemic control teams are very important and desirable to improve the quality and safety of care for inpatients with hyperglycemia and diabetes,” he said.

Regarding specific initiatives, such as those aimed at reducing hypoglycemia and insulin pen wastage, Dr. Maynard said, “All of these are feasible in a wide variety of institutions. The main barrier is getting the institutional support for people to work on these interventions. This series of studies can help spread the word about the positive return on investment.”

Another barrier – the current lack of publicly reported measures or pay-for-performance programs for hypoglycemia prevention and glycemic control – may soon change, added Dr. Maynard, who is also chief quality officer at the University of California, Davis, Medical Center.

“The National Quality Forum has endorsed new measures, and the CDC’s National Healthcare Safety Network is working on ways to augment those measures and embed them into their infrastructure,” he said.

Although SHM doesn’t specifically endorse full-time glycemic control hospitalists over endocrinology-trained glycemic control experts, “certainly hospitalists who accrue added training are very well positioned to be an important part of these interdisciplinary teams,” Dr. Maynard said.
 

‘The nurses were so afraid of hypoglycemia’

Tackling hypoglycemia was Dr. Zilbermint’s first priority when he started the glycemic management program at Suburban in late 2015.

“One of the most common complaints from the nurses was that a lot of their patients had hypoglycemia, especially in the ICU, when patients were placed on insulin infusion protocols ... Every time, the nurse would have to call the attending and ask what to do,” he explains.

In addition, Dr. Zilbermint says, there was no standard for treating hypoglycemia. A nurse in one unit would give two cups of juice, another a 50% dextrose infusion, or another, milk. Even more concerning, “the nurses were so afraid of hypoglycemia they would reflexively discontinue all insulin, including basal.”

So one of the new initiatives, led by Carter Shelton, MSHCM, an administrative fellow at the Medical University of South Carolina, Charleston, was to implement a set of hospital-wide hypoglycemia prevention measures, as described in an article published online April 21 in the Journal of Diabetes Science and Technology.
 

Inpatient hypoglycemia rate was cut nearly in half

This began in 2016, when the multidisciplinary Suburban Hospital Glucose Steering Committee identified four main causes of insulin-induced hypoglycemia (defined as a blood glucose level of ≤70 mg/dL in a patient who had received at least one dose of insulin in the past 24 hours) and devised solutions for each:

1. Lack of a unified hypoglycemia protocol. A formal, evidence-based, nurse-driven treatment protocol with clinical decision support in the electronic medical record was developed. The Suburban team adapted much of the protocol from one that had been recently implemented at the flagship Johns Hopkins Hospital, in Baltimore, Maryland.

According to that protocol, if patients are able to swallow, they are given 15 g or 30 g of carbohydrates in order to achieve a blood glucose level of 50 to 70 mg/dL and <50 mg/dL, respectively. Levels are checked 15 minutes later. Intravenous D50 or glucagon is reserved for patients who can’t swallow.

2. For patients in critical care, the insulin infusion protocol that had been in use set blood glucose targets of 80 to 110 mg/dL, which resulted in hypoglycemia in nearly every patient who received an insulin infusion. This protocol was changed to the currently recommended 140 to 180 mg/dL.

3. Most patients were managed with sliding-scale insulin, an outdated yet still widely used regimen whereby insulin is given based only on current blood glucose without accounting for carbohydrates consumed with meals and not corrected until the subsequent meal. This was changed so that nurses give insulin after the patient has consumed at least 50% of their meal carbohydrates.

4. Lack of hypoglycemia reporting. A glucometrics dashboard – now used throughout the Johns Hopkins system – was adopted to produce daily hypoglycemia reports in the EMR system that could be reviewed by the inpatient glucose management service to track quality metrics and plan further interventions.

Between Jan. 1, 2016, and Sept. 30, 2019, out of a total 49,315 patient-days, there were 2,682 days on which any hypoglycemia occurred and 874 days on which moderate hypoglycemia occurred (≤54 mg/dL). Type 2 diabetes accounted for 84.4% of the total patient-days; type 1 accounted for 4.4%.

The overall frequency of any hypoglycemia patient-days per month decreased from 7.5% to 3.9% during the study period (P = .001). This was significant for the patients with type 2 diabetes (7.4% to 3.8%; P < .0001) but not for those with type 1 diabetes (18.5% to 18.0%; P = .08).

Rates of moderate hypoglycemia also decreased significantly among the patients with type 2 diabetes (1.9% to 1.0%; P = .03) but not for those with type 1 diabetes (7.4% to 6.0%; P = .14).

On the basis of these rates in reducing hypoglycemia, in which the inpatient hypoglycemia rate was cut nearly in half, the estimated savings in cost of care to the hospital was $98,635 during the period of January 2016 to September 2019.
 

Reducing insulin pen waste by minimizing duplicate prescriptions

Suburban Hospital had been using insulin vials and syringes when Dr. Zilbermint first arrived there. He lobbied the administration to allow use of pens, because they’re easier to use and they reduce the risk for needlestick injuries. Nurses were educated and retrained monthly in their use.

The switch to pens – aspart (Novolog Flexpen) for bolus insulin and glargine (Lantus SoloSTAR) – took place in 2018. The cost of the aspart pen was $16.19, and the cost of glargine was $25.08. Each holds 300 units of insulin.

After the first month, the team noticed a large increase in expenses. A quality improvement project was devised to address the issue.

“We were dispensing sometimes three or four pens per person. That’s a lot. Each pen holds 300 units, so one pen should last the entire hospital stay of an average 4- or 5-day stay,” Dr. Zilbermint explained. “We had to figure out where we were bleeding the money and where the pens were going.”

When pens disappeared, the pharmacy would have to dispense new ones. One problem was that when patients were transferred from one unit to another, the pen would be left behind and the room would be cleaned. Sometimes the pens weren’t stored properly or were misplaced. Often, they’d end up in a nurse’s pocket.

The second intervention was led by Urooj Najmi, MD, of the American International School of Medicine, Atlanta, Georgia. A program was instituted to reduce duplicate inpatient insulin pen dispensing, as detailed in an article published in the same issue of the Journal of Diabetes Science and Technology.

Solutions to reduce duplicate pen dispensing included having pharmacy track daily insulin pen reports and monitor duplicate orders, with “do not dispense” instructions conveyed via the EMR system. All multidose medications, including insulin pens, were to be placed in patients’ bins at the nursing station, and nurses were instructed to look for patients’ insulin pens prior to their being transferred to another unit, rather than ask for a replacement pen.

From July 2018 to July 2019, 3,121 patients received insulin, of whom 95% received aspart and 47% received glargine. Of the 9,516 pens dispensed, 68% were for aspart and 32% were for glargine. During the study period, the number of pens dispensed per patient dropped from 2.2 to 1.2 for aspart and from 2.1 to 1.3 for glargine; differences were highly significant (P = .0002 and P = .0005, respectively).

The total amount of unnecessary dispensing during the first 4 months after initiating the pen implementation program was 58%. The average monthly cost was $11,820.68; the projected cost per year was $141,848.

Six months after the waste reduction strategies were implemented, monthly waste had dropped to 42%, translating to an estimated potential cost savings of $66,261 over 12 months.

Because Suburban Hospital doesn’t have an outpatient dispensing license, there is still wastage when patients are discharged, because they can’t take their pens home with them. That remains a challenge, Dr. Zilbermint noted.

The team is working on implementing automatic A1c testing for patients admitted with hyperglycemia who either have a history of diabetes or whose blood glucose level is >140 mg/dL. Dr. Zilbermint said, “it’s in the guidelines, but it’s not always done.”

Dr. Zilbermint is a consultant for Guidepoint. Dr. Maynard, Mr. Shelton, and Dr. Najmi have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Initiatives targeting hypoglycemia and insulin pen wastage could lead to dramatic cost savings in small community hospitals, new data suggest.

The two projects are part of a dedicated inpatient glucose management service led by Mihail (“Misha”) Zilbermint, MD, one of the few full-time endocrine hospitalists in the United States and one of even fewer who work at a small community hospital.

In 2019, Dr. Zilbermint and colleagues reported that their inpatient glucose management program resulted in a 27% reduction in length of stay and a 10.7% lower 30-day readmission rate. The projected cost savings for the period January 2016 to May 2017 was $953,578.

Dr. Zilbermint’s team has written two new articles that document cost savings for specific elements of the program; namely, a set of hospital-wide hypoglycemia prevention measures, and an initiative that reduced duplicate inpatient insulin pen dispensing.

About 1 in 4 people in U.S. hospitals have diabetes or hyperglycemia. Large academic hospitals have endocrine divisions and training programs, but 85% of people receive care at small community hospitals.

“There are management guidelines, but they’re not always followed ... That’s why I’ve been advocating for endocrine hospitalists to be deployed nationally,” Dr. Zilbermint said. He is chief and director of endocrinology, diabetes, and metabolism at Johns Hopkins Community Physicians at Suburban Hospital, Bethesda, Maryland.

Asked to comment on behalf of the Society of Hospital Medicine (SHM), Greg Maynard, MD, program lead for SHM’s Electronic Quality Improvement Programs, said that Suburban’s overall program goals align with those of the SHM.

“Dedicated inpatient glycemic control teams are very important and desirable to improve the quality and safety of care for inpatients with hyperglycemia and diabetes,” he said.

Regarding specific initiatives, such as those aimed at reducing hypoglycemia and insulin pen wastage, Dr. Maynard said, “All of these are feasible in a wide variety of institutions. The main barrier is getting the institutional support for people to work on these interventions. This series of studies can help spread the word about the positive return on investment.”

Another barrier – the current lack of publicly reported measures or pay-for-performance programs for hypoglycemia prevention and glycemic control – may soon change, added Dr. Maynard, who is also chief quality officer at the University of California, Davis, Medical Center.

“The National Quality Forum has endorsed new measures, and the CDC’s National Healthcare Safety Network is working on ways to augment those measures and embed them into their infrastructure,” he said.

Although SHM doesn’t specifically endorse full-time glycemic control hospitalists over endocrinology-trained glycemic control experts, “certainly hospitalists who accrue added training are very well positioned to be an important part of these interdisciplinary teams,” Dr. Maynard said.
 

‘The nurses were so afraid of hypoglycemia’

Tackling hypoglycemia was Dr. Zilbermint’s first priority when he started the glycemic management program at Suburban in late 2015.

“One of the most common complaints from the nurses was that a lot of their patients had hypoglycemia, especially in the ICU, when patients were placed on insulin infusion protocols ... Every time, the nurse would have to call the attending and ask what to do,” he explains.

In addition, Dr. Zilbermint says, there was no standard for treating hypoglycemia. A nurse in one unit would give two cups of juice, another a 50% dextrose infusion, or another, milk. Even more concerning, “the nurses were so afraid of hypoglycemia they would reflexively discontinue all insulin, including basal.”

So one of the new initiatives, led by Carter Shelton, MSHCM, an administrative fellow at the Medical University of South Carolina, Charleston, was to implement a set of hospital-wide hypoglycemia prevention measures, as described in an article published online April 21 in the Journal of Diabetes Science and Technology.
 

Inpatient hypoglycemia rate was cut nearly in half

This began in 2016, when the multidisciplinary Suburban Hospital Glucose Steering Committee identified four main causes of insulin-induced hypoglycemia (defined as a blood glucose level of ≤70 mg/dL in a patient who had received at least one dose of insulin in the past 24 hours) and devised solutions for each:

1. Lack of a unified hypoglycemia protocol. A formal, evidence-based, nurse-driven treatment protocol with clinical decision support in the electronic medical record was developed. The Suburban team adapted much of the protocol from one that had been recently implemented at the flagship Johns Hopkins Hospital, in Baltimore, Maryland.

According to that protocol, if patients are able to swallow, they are given 15 g or 30 g of carbohydrates in order to achieve a blood glucose level of 50 to 70 mg/dL and <50 mg/dL, respectively. Levels are checked 15 minutes later. Intravenous D50 or glucagon is reserved for patients who can’t swallow.

2. For patients in critical care, the insulin infusion protocol that had been in use set blood glucose targets of 80 to 110 mg/dL, which resulted in hypoglycemia in nearly every patient who received an insulin infusion. This protocol was changed to the currently recommended 140 to 180 mg/dL.

3. Most patients were managed with sliding-scale insulin, an outdated yet still widely used regimen whereby insulin is given based only on current blood glucose without accounting for carbohydrates consumed with meals and not corrected until the subsequent meal. This was changed so that nurses give insulin after the patient has consumed at least 50% of their meal carbohydrates.

4. Lack of hypoglycemia reporting. A glucometrics dashboard – now used throughout the Johns Hopkins system – was adopted to produce daily hypoglycemia reports in the EMR system that could be reviewed by the inpatient glucose management service to track quality metrics and plan further interventions.

Between Jan. 1, 2016, and Sept. 30, 2019, out of a total 49,315 patient-days, there were 2,682 days on which any hypoglycemia occurred and 874 days on which moderate hypoglycemia occurred (≤54 mg/dL). Type 2 diabetes accounted for 84.4% of the total patient-days; type 1 accounted for 4.4%.

The overall frequency of any hypoglycemia patient-days per month decreased from 7.5% to 3.9% during the study period (P = .001). This was significant for the patients with type 2 diabetes (7.4% to 3.8%; P < .0001) but not for those with type 1 diabetes (18.5% to 18.0%; P = .08).

Rates of moderate hypoglycemia also decreased significantly among the patients with type 2 diabetes (1.9% to 1.0%; P = .03) but not for those with type 1 diabetes (7.4% to 6.0%; P = .14).

On the basis of these rates in reducing hypoglycemia, in which the inpatient hypoglycemia rate was cut nearly in half, the estimated savings in cost of care to the hospital was $98,635 during the period of January 2016 to September 2019.
 

Reducing insulin pen waste by minimizing duplicate prescriptions

Suburban Hospital had been using insulin vials and syringes when Dr. Zilbermint first arrived there. He lobbied the administration to allow use of pens, because they’re easier to use and they reduce the risk for needlestick injuries. Nurses were educated and retrained monthly in their use.

The switch to pens – aspart (Novolog Flexpen) for bolus insulin and glargine (Lantus SoloSTAR) – took place in 2018. The cost of the aspart pen was $16.19, and the cost of glargine was $25.08. Each holds 300 units of insulin.

After the first month, the team noticed a large increase in expenses. A quality improvement project was devised to address the issue.

“We were dispensing sometimes three or four pens per person. That’s a lot. Each pen holds 300 units, so one pen should last the entire hospital stay of an average 4- or 5-day stay,” Dr. Zilbermint explained. “We had to figure out where we were bleeding the money and where the pens were going.”

When pens disappeared, the pharmacy would have to dispense new ones. One problem was that when patients were transferred from one unit to another, the pen would be left behind and the room would be cleaned. Sometimes the pens weren’t stored properly or were misplaced. Often, they’d end up in a nurse’s pocket.

The second intervention was led by Urooj Najmi, MD, of the American International School of Medicine, Atlanta, Georgia. A program was instituted to reduce duplicate inpatient insulin pen dispensing, as detailed in an article published in the same issue of the Journal of Diabetes Science and Technology.

Solutions to reduce duplicate pen dispensing included having pharmacy track daily insulin pen reports and monitor duplicate orders, with “do not dispense” instructions conveyed via the EMR system. All multidose medications, including insulin pens, were to be placed in patients’ bins at the nursing station, and nurses were instructed to look for patients’ insulin pens prior to their being transferred to another unit, rather than ask for a replacement pen.

From July 2018 to July 2019, 3,121 patients received insulin, of whom 95% received aspart and 47% received glargine. Of the 9,516 pens dispensed, 68% were for aspart and 32% were for glargine. During the study period, the number of pens dispensed per patient dropped from 2.2 to 1.2 for aspart and from 2.1 to 1.3 for glargine; differences were highly significant (P = .0002 and P = .0005, respectively).

The total amount of unnecessary dispensing during the first 4 months after initiating the pen implementation program was 58%. The average monthly cost was $11,820.68; the projected cost per year was $141,848.

Six months after the waste reduction strategies were implemented, monthly waste had dropped to 42%, translating to an estimated potential cost savings of $66,261 over 12 months.

Because Suburban Hospital doesn’t have an outpatient dispensing license, there is still wastage when patients are discharged, because they can’t take their pens home with them. That remains a challenge, Dr. Zilbermint noted.

The team is working on implementing automatic A1c testing for patients admitted with hyperglycemia who either have a history of diabetes or whose blood glucose level is >140 mg/dL. Dr. Zilbermint said, “it’s in the guidelines, but it’s not always done.”

Dr. Zilbermint is a consultant for Guidepoint. Dr. Maynard, Mr. Shelton, and Dr. Najmi have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”

You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?

The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.

The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.

The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.

But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.

As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.

At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.

We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.

The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.

The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.

With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.

We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.

Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
 

You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?

First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.

The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.

I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
 

Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?

As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.

In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.

I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.

That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.

All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.

Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.

In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.

There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
 

What do you think it will take to achieve herd immunity?

I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.

It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.

We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.

People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.

Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.

That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.

A version of this article first appeared on Medscape.com.

Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”

You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?

The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.

The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.

The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.

But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.

As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.

At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.

We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.

The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.

The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.

With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.

We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.

Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
 

You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?

First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.

The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.

I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
 

Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?

As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.

In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.

I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.

That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.

All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.

Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.

In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.

There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
 

What do you think it will take to achieve herd immunity?

I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.

It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.

We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.

People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.

Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.

That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.

A version of this article first appeared on Medscape.com.

Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”

You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?

The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.

The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.

The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.

But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.

As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.

At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.

We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.

The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.

The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.

With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.

We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.

Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
 

You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?

First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.

The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.

I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
 

Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?

As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.

In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.

I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.

That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.

All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.

Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.

In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.

There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
 

What do you think it will take to achieve herd immunity?

I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.

It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.

We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.

People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.

Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.

That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.

A version of this article first appeared on Medscape.com.

In 2017-2018, only one in three U.S. adults with diabetes received five basic elements of care recommended by the American Diabetes Association, new research indicates.

BakiBG

The proportions of patients who visited a physician for diabetes care and received hemoglobin A1c testing, foot and eye exams, and cholesterol testing increased from 2005 to 2018. However, this increase was primarily among those aged 65 years and older, and therefore eligible for Medicare.

“Our study suggests that providing affordable health care coverage can help ensure people with diabetes get recommended care. We also found that patients who were not receiving recommended care were more likely to be younger, newly diagnosed with diabetes, and not on diabetes medication. Clinicians can pay more attention to these patient populations to improve recommended care delivery and prevent diabetes-related complications,” lead author Jung-Im Shin, MD, said in an interview.

The data predate the COVID-19 pandemic, which has also had major effects on delivery of diabetes care, added Dr. Shin of Johns Hopkins University, Baltimore.

“Routine visits to the doctor and important screenings for retinopathy or foot examination have been postponed. People with diabetes have had to reschedule or cancel nonurgent visits, some have lost ... insurance following unemployment, and many have avoided health care facilities out of fear. We are only just beginning to understand the consequences of the pandemic on the health of people with diabetes,” Dr. Shin noted.
 

Overall improvements seen only in those aged 65 and older

The data, from 4,069 adults aged 20 years and older from the 2005-2018 National Health and Nutrition and Examination Survey (NHANES), were published online April 16, 2021, in Diabetes Care.

Dr. Shin and colleagues defined receipt of diabetes care as meeting all of the following five criteria in the past 12 months, based on the ADA Standards of Care and NHANES data availability: seeing a primary doctor for diabetes care, receiving A1c testing, receiving a foot examination, receiving an eye examination, and receiving cholesterol testing.

Over the entire 13-year period, 29.2% of respondents reported having received all five components.

That proportion increased significantly over time, from 25.0% in 2005-2006 to 34.1% in 2017-2018 (P = .004). However, among the individual components, only receiving A1c testing increased significantly over time, from 64.4% to 85.3%, in all age groups (P < .001).

Moreover, when stratified by age, receipt of all five components only increased significantly among participants aged 65 and older, from 29.3% in 2005-2006 to 44.2% in 2017-2018 (P = .001).

The proportion remained unchanged among those aged 40-64 (25.2% to 25.8%; P =  .457) and showed a nonsignificant increase in those aged 20-39 (9.9% to 26.0%; P = .401).

In adjusted analyses, older age, higher income and education, health insurance, longer duration of diabetes, use of diabetes medications, and hypercholesterolemia were significantly associated with receipt of ADA guideline–recommended diabetes care.

Factors not found to be associated with care receipt included sex, race/ethnicity, body mass index, smoking status, A1c, hypertension, cardiovascular disease, chronic kidney disease, and depressive symptoms.

Participants who received ADA guideline–recommended care were significantly more likely to achieve A1c below 7.5% (adjusted odds ratio, 1.52), blood pressure less than 140/90 mm Hg (aOR, 1.47), and LDL cholesterol below 100 mg/dL (aOR, 1.47), and to receive cholesterol-lowering medication (aOR, 1.79).

Dr. Shin said that it will be “important to study the impact of COVID-19 on diabetes care when new data are available.”

The project was supported by a research grant from Merck to Johns Hopkins University. Shin has reported receiving a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Two coauthors are Merck employees.

A version of this article first appeared on Medscape.com.

In 2017-2018, only one in three U.S. adults with diabetes received five basic elements of care recommended by the American Diabetes Association, new research indicates.

BakiBG

The proportions of patients who visited a physician for diabetes care and received hemoglobin A1c testing, foot and eye exams, and cholesterol testing increased from 2005 to 2018. However, this increase was primarily among those aged 65 years and older, and therefore eligible for Medicare.

“Our study suggests that providing affordable health care coverage can help ensure people with diabetes get recommended care. We also found that patients who were not receiving recommended care were more likely to be younger, newly diagnosed with diabetes, and not on diabetes medication. Clinicians can pay more attention to these patient populations to improve recommended care delivery and prevent diabetes-related complications,” lead author Jung-Im Shin, MD, said in an interview.

The data predate the COVID-19 pandemic, which has also had major effects on delivery of diabetes care, added Dr. Shin of Johns Hopkins University, Baltimore.

“Routine visits to the doctor and important screenings for retinopathy or foot examination have been postponed. People with diabetes have had to reschedule or cancel nonurgent visits, some have lost ... insurance following unemployment, and many have avoided health care facilities out of fear. We are only just beginning to understand the consequences of the pandemic on the health of people with diabetes,” Dr. Shin noted.
 

Overall improvements seen only in those aged 65 and older

The data, from 4,069 adults aged 20 years and older from the 2005-2018 National Health and Nutrition and Examination Survey (NHANES), were published online April 16, 2021, in Diabetes Care.

Dr. Shin and colleagues defined receipt of diabetes care as meeting all of the following five criteria in the past 12 months, based on the ADA Standards of Care and NHANES data availability: seeing a primary doctor for diabetes care, receiving A1c testing, receiving a foot examination, receiving an eye examination, and receiving cholesterol testing.

Over the entire 13-year period, 29.2% of respondents reported having received all five components.

That proportion increased significantly over time, from 25.0% in 2005-2006 to 34.1% in 2017-2018 (P = .004). However, among the individual components, only receiving A1c testing increased significantly over time, from 64.4% to 85.3%, in all age groups (P < .001).

Moreover, when stratified by age, receipt of all five components only increased significantly among participants aged 65 and older, from 29.3% in 2005-2006 to 44.2% in 2017-2018 (P = .001).

The proportion remained unchanged among those aged 40-64 (25.2% to 25.8%; P =  .457) and showed a nonsignificant increase in those aged 20-39 (9.9% to 26.0%; P = .401).

In adjusted analyses, older age, higher income and education, health insurance, longer duration of diabetes, use of diabetes medications, and hypercholesterolemia were significantly associated with receipt of ADA guideline–recommended diabetes care.

Factors not found to be associated with care receipt included sex, race/ethnicity, body mass index, smoking status, A1c, hypertension, cardiovascular disease, chronic kidney disease, and depressive symptoms.

Participants who received ADA guideline–recommended care were significantly more likely to achieve A1c below 7.5% (adjusted odds ratio, 1.52), blood pressure less than 140/90 mm Hg (aOR, 1.47), and LDL cholesterol below 100 mg/dL (aOR, 1.47), and to receive cholesterol-lowering medication (aOR, 1.79).

Dr. Shin said that it will be “important to study the impact of COVID-19 on diabetes care when new data are available.”

The project was supported by a research grant from Merck to Johns Hopkins University. Shin has reported receiving a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Two coauthors are Merck employees.

A version of this article first appeared on Medscape.com.

In 2017-2018, only one in three U.S. adults with diabetes received five basic elements of care recommended by the American Diabetes Association, new research indicates.

BakiBG

The proportions of patients who visited a physician for diabetes care and received hemoglobin A1c testing, foot and eye exams, and cholesterol testing increased from 2005 to 2018. However, this increase was primarily among those aged 65 years and older, and therefore eligible for Medicare.

“Our study suggests that providing affordable health care coverage can help ensure people with diabetes get recommended care. We also found that patients who were not receiving recommended care were more likely to be younger, newly diagnosed with diabetes, and not on diabetes medication. Clinicians can pay more attention to these patient populations to improve recommended care delivery and prevent diabetes-related complications,” lead author Jung-Im Shin, MD, said in an interview.

The data predate the COVID-19 pandemic, which has also had major effects on delivery of diabetes care, added Dr. Shin of Johns Hopkins University, Baltimore.

“Routine visits to the doctor and important screenings for retinopathy or foot examination have been postponed. People with diabetes have had to reschedule or cancel nonurgent visits, some have lost ... insurance following unemployment, and many have avoided health care facilities out of fear. We are only just beginning to understand the consequences of the pandemic on the health of people with diabetes,” Dr. Shin noted.
 

Overall improvements seen only in those aged 65 and older

The data, from 4,069 adults aged 20 years and older from the 2005-2018 National Health and Nutrition and Examination Survey (NHANES), were published online April 16, 2021, in Diabetes Care.

Dr. Shin and colleagues defined receipt of diabetes care as meeting all of the following five criteria in the past 12 months, based on the ADA Standards of Care and NHANES data availability: seeing a primary doctor for diabetes care, receiving A1c testing, receiving a foot examination, receiving an eye examination, and receiving cholesterol testing.

Over the entire 13-year period, 29.2% of respondents reported having received all five components.

That proportion increased significantly over time, from 25.0% in 2005-2006 to 34.1% in 2017-2018 (P = .004). However, among the individual components, only receiving A1c testing increased significantly over time, from 64.4% to 85.3%, in all age groups (P < .001).

Moreover, when stratified by age, receipt of all five components only increased significantly among participants aged 65 and older, from 29.3% in 2005-2006 to 44.2% in 2017-2018 (P = .001).

The proportion remained unchanged among those aged 40-64 (25.2% to 25.8%; P =  .457) and showed a nonsignificant increase in those aged 20-39 (9.9% to 26.0%; P = .401).

In adjusted analyses, older age, higher income and education, health insurance, longer duration of diabetes, use of diabetes medications, and hypercholesterolemia were significantly associated with receipt of ADA guideline–recommended diabetes care.

Factors not found to be associated with care receipt included sex, race/ethnicity, body mass index, smoking status, A1c, hypertension, cardiovascular disease, chronic kidney disease, and depressive symptoms.

Participants who received ADA guideline–recommended care were significantly more likely to achieve A1c below 7.5% (adjusted odds ratio, 1.52), blood pressure less than 140/90 mm Hg (aOR, 1.47), and LDL cholesterol below 100 mg/dL (aOR, 1.47), and to receive cholesterol-lowering medication (aOR, 1.79).

Dr. Shin said that it will be “important to study the impact of COVID-19 on diabetes care when new data are available.”

The project was supported by a research grant from Merck to Johns Hopkins University. Shin has reported receiving a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Two coauthors are Merck employees.

A version of this article first appeared on Medscape.com.

The majority of children with type 1 diabetes who tested positive for SARS-CoV-2 were cared for at home and did well, according to the first report of outcomes of pediatric patients with type 1 diabetes and COVID-19 from the United States.

Most children who were hospitalized had diabetic ketoacidosis (DKA) and high hemoglobin A1c levels, the new report from the T1D Exchange Quality Improvement Collaborative indicates. Fewer than 2% required respiratory support, and no deaths were recorded.

The greatest risk for adverse COVID-19 outcomes was among children with A1c levels >9%. In addition, children of certain ethnic minority groups and those with public health insurance were more likely to be hospitalized.

The study, conducted by G. Todd Alonso, MD, of the University of Colorado, Barbara Davis Center, Aurora, and colleagues, was published online April 14 in the Journal of Diabetes..

“As early reports identified diabetes as a risk factor for increased morbidity and mortality with COVID-19, the findings from this surveillance study should provide measured reassurance for families of children with type 1 diabetes as well as pediatric endocrinologists and their care teams,” say Dr. Alonso and colleagues.
 

Disproportionate rate of hospitalization, DKA among Black patients

Initiated in April 2020, the T1D Exchange Quality Improvement Collaborative comprises 56 diabetes centers, of which 52 submitted a total of 266 cases involving patients younger than 19 years who had type 1 diabetes and who tested positive for SARS-CoV-2 infection. Those with new-onset type 1 diabetes were excluded from this analysis and were reported separately. The data were collected between April 9, 2020, and Jan. 15, 2021.

Of the 266 patients, 23% (61) were hospitalized, and 205 were not. There were no differences by age, gender, or diabetes duration.

However, those hospitalized were more likely to be Black (34% vs. 13% among White patients; P < .001) and to have public health insurance (64% vs. 41%; P < .001). They also had higher A1c levels than patients who were not hospitalized (11% vs. 8.2%; P < .001), and fewer used insulin pumps (26% vs. 54%; P < .001) and continuous glucose monitors (39% vs. 75%; P < .001).

Those hospitalized were also more likely to have hyperglycemia (48% vs. 28%; P = .007), nausea (33% vs. 6%; P < .001), and vomiting (49% vs. 3%; P < .001). Rates of dry cough, excess fatigue, and body aches/headaches did not differ between those hospitalized and those who remained at home.

The most common adverse outcome was DKA, which occurred in 72% (44) of those hospitalized.

The most recent A1c level was less than 9% in 82% of those hospitalized vs. 31% of those who weren’t (P < .001) and in 38 of the 44 (86%) who had DKA.

“Our data reveal a disproportionate rate of hospitalization and DKA among racial and ethnic minority groups, children who were publicly insured, and those with higher A1c. It is essential to find pathways for the most vulnerable patients to have adequate, equitable access to medical care via in person and telehealth services, to obtain and successfully use diabetes technology, and to optimize sick day management,” say Dr. Alonso and colleagues.

One child, a 15-year-old White boy, underwent intubation and was placed on a ventilator. His most recent A1c was 8.9%. Another child, a 13-year-old boy whose most recent A1c level was 11.1%, developed multisystem inflammatory syndrome of childhood.

The registry remains open.

The T1D Exchange QI Collaborative is funded by the Helmsley Charitable Trust. The T1D Exchange received partial financial support for this study from Abbott Diabetes, Dexcom, Medtronic, Insulet Corporation, JDRF, Eli Lilly, and Tandem Diabetes Care. None of the sponsors were involved in initiating, designing, or preparing the manuscript for this study.

A version of this article first appeared on Medscape.com.

The majority of children with type 1 diabetes who tested positive for SARS-CoV-2 were cared for at home and did well, according to the first report of outcomes of pediatric patients with type 1 diabetes and COVID-19 from the United States.

Most children who were hospitalized had diabetic ketoacidosis (DKA) and high hemoglobin A1c levels, the new report from the T1D Exchange Quality Improvement Collaborative indicates. Fewer than 2% required respiratory support, and no deaths were recorded.

The greatest risk for adverse COVID-19 outcomes was among children with A1c levels >9%. In addition, children of certain ethnic minority groups and those with public health insurance were more likely to be hospitalized.

The study, conducted by G. Todd Alonso, MD, of the University of Colorado, Barbara Davis Center, Aurora, and colleagues, was published online April 14 in the Journal of Diabetes..

“As early reports identified diabetes as a risk factor for increased morbidity and mortality with COVID-19, the findings from this surveillance study should provide measured reassurance for families of children with type 1 diabetes as well as pediatric endocrinologists and their care teams,” say Dr. Alonso and colleagues.
 

Disproportionate rate of hospitalization, DKA among Black patients

Initiated in April 2020, the T1D Exchange Quality Improvement Collaborative comprises 56 diabetes centers, of which 52 submitted a total of 266 cases involving patients younger than 19 years who had type 1 diabetes and who tested positive for SARS-CoV-2 infection. Those with new-onset type 1 diabetes were excluded from this analysis and were reported separately. The data were collected between April 9, 2020, and Jan. 15, 2021.

Of the 266 patients, 23% (61) were hospitalized, and 205 were not. There were no differences by age, gender, or diabetes duration.

However, those hospitalized were more likely to be Black (34% vs. 13% among White patients; P < .001) and to have public health insurance (64% vs. 41%; P < .001). They also had higher A1c levels than patients who were not hospitalized (11% vs. 8.2%; P < .001), and fewer used insulin pumps (26% vs. 54%; P < .001) and continuous glucose monitors (39% vs. 75%; P < .001).

Those hospitalized were also more likely to have hyperglycemia (48% vs. 28%; P = .007), nausea (33% vs. 6%; P < .001), and vomiting (49% vs. 3%; P < .001). Rates of dry cough, excess fatigue, and body aches/headaches did not differ between those hospitalized and those who remained at home.

The most common adverse outcome was DKA, which occurred in 72% (44) of those hospitalized.

The most recent A1c level was less than 9% in 82% of those hospitalized vs. 31% of those who weren’t (P < .001) and in 38 of the 44 (86%) who had DKA.

“Our data reveal a disproportionate rate of hospitalization and DKA among racial and ethnic minority groups, children who were publicly insured, and those with higher A1c. It is essential to find pathways for the most vulnerable patients to have adequate, equitable access to medical care via in person and telehealth services, to obtain and successfully use diabetes technology, and to optimize sick day management,” say Dr. Alonso and colleagues.

One child, a 15-year-old White boy, underwent intubation and was placed on a ventilator. His most recent A1c was 8.9%. Another child, a 13-year-old boy whose most recent A1c level was 11.1%, developed multisystem inflammatory syndrome of childhood.

The registry remains open.

The T1D Exchange QI Collaborative is funded by the Helmsley Charitable Trust. The T1D Exchange received partial financial support for this study from Abbott Diabetes, Dexcom, Medtronic, Insulet Corporation, JDRF, Eli Lilly, and Tandem Diabetes Care. None of the sponsors were involved in initiating, designing, or preparing the manuscript for this study.

A version of this article first appeared on Medscape.com.

The majority of children with type 1 diabetes who tested positive for SARS-CoV-2 were cared for at home and did well, according to the first report of outcomes of pediatric patients with type 1 diabetes and COVID-19 from the United States.

Most children who were hospitalized had diabetic ketoacidosis (DKA) and high hemoglobin A1c levels, the new report from the T1D Exchange Quality Improvement Collaborative indicates. Fewer than 2% required respiratory support, and no deaths were recorded.

The greatest risk for adverse COVID-19 outcomes was among children with A1c levels >9%. In addition, children of certain ethnic minority groups and those with public health insurance were more likely to be hospitalized.

The study, conducted by G. Todd Alonso, MD, of the University of Colorado, Barbara Davis Center, Aurora, and colleagues, was published online April 14 in the Journal of Diabetes..

“As early reports identified diabetes as a risk factor for increased morbidity and mortality with COVID-19, the findings from this surveillance study should provide measured reassurance for families of children with type 1 diabetes as well as pediatric endocrinologists and their care teams,” say Dr. Alonso and colleagues.
 

Disproportionate rate of hospitalization, DKA among Black patients

Initiated in April 2020, the T1D Exchange Quality Improvement Collaborative comprises 56 diabetes centers, of which 52 submitted a total of 266 cases involving patients younger than 19 years who had type 1 diabetes and who tested positive for SARS-CoV-2 infection. Those with new-onset type 1 diabetes were excluded from this analysis and were reported separately. The data were collected between April 9, 2020, and Jan. 15, 2021.

Of the 266 patients, 23% (61) were hospitalized, and 205 were not. There were no differences by age, gender, or diabetes duration.

However, those hospitalized were more likely to be Black (34% vs. 13% among White patients; P < .001) and to have public health insurance (64% vs. 41%; P < .001). They also had higher A1c levels than patients who were not hospitalized (11% vs. 8.2%; P < .001), and fewer used insulin pumps (26% vs. 54%; P < .001) and continuous glucose monitors (39% vs. 75%; P < .001).

Those hospitalized were also more likely to have hyperglycemia (48% vs. 28%; P = .007), nausea (33% vs. 6%; P < .001), and vomiting (49% vs. 3%; P < .001). Rates of dry cough, excess fatigue, and body aches/headaches did not differ between those hospitalized and those who remained at home.

The most common adverse outcome was DKA, which occurred in 72% (44) of those hospitalized.

The most recent A1c level was less than 9% in 82% of those hospitalized vs. 31% of those who weren’t (P < .001) and in 38 of the 44 (86%) who had DKA.

“Our data reveal a disproportionate rate of hospitalization and DKA among racial and ethnic minority groups, children who were publicly insured, and those with higher A1c. It is essential to find pathways for the most vulnerable patients to have adequate, equitable access to medical care via in person and telehealth services, to obtain and successfully use diabetes technology, and to optimize sick day management,” say Dr. Alonso and colleagues.

One child, a 15-year-old White boy, underwent intubation and was placed on a ventilator. His most recent A1c was 8.9%. Another child, a 13-year-old boy whose most recent A1c level was 11.1%, developed multisystem inflammatory syndrome of childhood.

The registry remains open.

The T1D Exchange QI Collaborative is funded by the Helmsley Charitable Trust. The T1D Exchange received partial financial support for this study from Abbott Diabetes, Dexcom, Medtronic, Insulet Corporation, JDRF, Eli Lilly, and Tandem Diabetes Care. None of the sponsors were involved in initiating, designing, or preparing the manuscript for this study.

A version of this article first appeared on Medscape.com.

Two new phase 2 studies show encouraging findings with the investigational once-weekly basal insulin analogue icodec (Novo Nordisk) for people with type 2 diabetes who require insulin.

Sara Freeman/MDedge News

Insulin icodec works by reversibly binding to albumin, which slows the release of the active insulin analogue. It has a half-life of about 1 week. The glucose-lowering effect is distributed nearly evenly over the course of that week.

Ildiko Lingvay, MD, of the University of Texas Southwestern Medical Center, Dallas, who is an author of both new articles, said: “A weekly insulin is a game changer that will decrease the treatment burden for patients while also improving compliance.”

She noted that these studies demonstrate optimal approaches to initiating treatment with icodec and serve “as the steppingstones for a large phase 3 clinical trial program that is currently ongoing ... which is designed to evaluate the efficacy of once-weekly insulin administration in patients with either type 1 or type 2 diabetes.”

Another advantage of the formulation, Dr. Lingvay pointed out in a press release from her institution, is that it could decrease the burden on caregivers of patients with diabetes who require insulin.

“For example, for patients who need help injecting, those living in long-term care facilities, and those with memory problems, a once-weekly insulin will facilitate treatment and decrease the burden on the care providers,” she explained.
 

Titration balances glycemic control with hypoglycemic risk reduction

The first phase 2 trial, published online April 19, 2021, in Diabetes Care, was an open-label, 16-week, treat-to-target study that involved 205 insulin-naive adults with type 2 diabetes whose hemoglobin A1c levels were 7%-10% while using oral glucose-lowering medications.

They were randomly assigned to one of three once-weekly icodec titration groups:

• Group A – Fasting glucose target of 80-130 mg/dL with adjustments ±21 units/wk
• Group B – Fasting glucose target of 80-130 mg/dL with ±28 units/wk
• Group C – Fasting glucose target of 70-108 mg/dL, adjusting by ±28 units/wk or to once-daily glargine U100 with a fasting glucose target of 80-130 mg/dL with adjustments of ±4 units/d

The percentage of time in the ideal glucose range of 70-180 mg/dL, assessed by continuous glucose monitoring during weeks 15-16, improved from baseline levels of 57.0%, 55.2%, 51.0% for groups A, B, and C, respectively, and from 55.3% for glargine to 76.6%, 83.0%, 80.9%, and 75.9%, respectively.

There were no unexpected safety problems. Hypoglycemia episodes of glucose levels <54 mg/dL occurred in 0.05, 0.15, 0.38, and 0.00 per patient-year for the four groups, respectively. None were severe (i.e., required assistance).

The titration for patients in group A (80-130 mg/dL, ±21 units/wk) yielded the best balance between glycemic control and risk for hypoglycemia, Dr. Lingvay and colleagues said.
 

Use of loading dose when switching to icodec improves time in range

In the other phase 2 trial, also published online April 19 in Diabetes Care, Harpreet S. Bajaj, MD, of Mount Sinai Hospital, Toronto, and colleagues, with Dr. Lingvay as a coauthor, examined two methods of switching to icodec. This multicenter, open-label, treat-to-target study included 154 patients with A1c levels of 7-10% who were already receiving basal insulin daily and at least one oral glucose-lowering medication.

Patients were randomly assigned to one of three treatment approaches: a 100% loading dose of icodec (only the first dose was doubled), no loading dose, or once-daily glargine.

The primary endpoint was time in range (70-180 mg/dL) during weeks 15 and 16. This was achieved with 72.9% of patients receiving the icodec loading dose, 66.0% of patients receiving icodec without the loading dose, and 65.0% of patients receiving daily glargine. The difference between the icodec loading-dose method and glargine was significant, Dr. Bajaj and colleagues reported.

The mean A1c level was reduced from an overall average of 7.9% at baseline to 7.1% in the icodec loading dose group and to 7.4% in both the no-loading-dose and glargine groups.

Rates of adverse events and hypoglycemic episodes did not differ significantly among the groups.

Previous phase 2 data showing that the efficacy and safety of icodec were comparable with that of once-daily insulin glargine U100 in 247 insulin-naive patients with type 2 diabetes were published in November 2020 in the New England Journal of Medicine and were presented at the European Association for the Study of Diabetes (EASD) 2020 Annual Meeting, as reported by this news organization.

Both studies were funded by Novo Nordisk. Dr. Lingvey has received research funding, advisory/consulting fees, or other support from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Boehringer Ingelheim, Janssen, Intercept, Intarcia, Target RWE, Merck, Pfizer, Novartis, GI Dynamics, Mylan, Mannkind, Valeritas, Bayer, and Zealand Pharma. Dr. Bajaj has received speaking fees from AstraZeneca, Eli Lilly, Janssen Pharmaceuticals, Merck, and Novo Nordisk and research funding paid to LMC Healthcare for serving as principal investigator on clinical trials from Amgen, AstraZeneca Boehringer Ingelheim, Ceapro Inc, Eli Lilly, Gilead Sciences, Janssen Pharmaceuticals, Kowa Pharmaceuticals, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Sanofi, and Tricida.

A version of this article first appeared on Medscape.com.

Two new phase 2 studies show encouraging findings with the investigational once-weekly basal insulin analogue icodec (Novo Nordisk) for people with type 2 diabetes who require insulin.

Sara Freeman/MDedge News

Insulin icodec works by reversibly binding to albumin, which slows the release of the active insulin analogue. It has a half-life of about 1 week. The glucose-lowering effect is distributed nearly evenly over the course of that week.

Ildiko Lingvay, MD, of the University of Texas Southwestern Medical Center, Dallas, who is an author of both new articles, said: “A weekly insulin is a game changer that will decrease the treatment burden for patients while also improving compliance.”

She noted that these studies demonstrate optimal approaches to initiating treatment with icodec and serve “as the steppingstones for a large phase 3 clinical trial program that is currently ongoing ... which is designed to evaluate the efficacy of once-weekly insulin administration in patients with either type 1 or type 2 diabetes.”

Another advantage of the formulation, Dr. Lingvay pointed out in a press release from her institution, is that it could decrease the burden on caregivers of patients with diabetes who require insulin.

“For example, for patients who need help injecting, those living in long-term care facilities, and those with memory problems, a once-weekly insulin will facilitate treatment and decrease the burden on the care providers,” she explained.
 

Titration balances glycemic control with hypoglycemic risk reduction

The first phase 2 trial, published online April 19, 2021, in Diabetes Care, was an open-label, 16-week, treat-to-target study that involved 205 insulin-naive adults with type 2 diabetes whose hemoglobin A1c levels were 7%-10% while using oral glucose-lowering medications.

They were randomly assigned to one of three once-weekly icodec titration groups:

• Group A – Fasting glucose target of 80-130 mg/dL with adjustments ±21 units/wk
• Group B – Fasting glucose target of 80-130 mg/dL with ±28 units/wk
• Group C – Fasting glucose target of 70-108 mg/dL, adjusting by ±28 units/wk or to once-daily glargine U100 with a fasting glucose target of 80-130 mg/dL with adjustments of ±4 units/d

The percentage of time in the ideal glucose range of 70-180 mg/dL, assessed by continuous glucose monitoring during weeks 15-16, improved from baseline levels of 57.0%, 55.2%, 51.0% for groups A, B, and C, respectively, and from 55.3% for glargine to 76.6%, 83.0%, 80.9%, and 75.9%, respectively.

There were no unexpected safety problems. Hypoglycemia episodes of glucose levels <54 mg/dL occurred in 0.05, 0.15, 0.38, and 0.00 per patient-year for the four groups, respectively. None were severe (i.e., required assistance).

The titration for patients in group A (80-130 mg/dL, ±21 units/wk) yielded the best balance between glycemic control and risk for hypoglycemia, Dr. Lingvay and colleagues said.
 

Use of loading dose when switching to icodec improves time in range

In the other phase 2 trial, also published online April 19 in Diabetes Care, Harpreet S. Bajaj, MD, of Mount Sinai Hospital, Toronto, and colleagues, with Dr. Lingvay as a coauthor, examined two methods of switching to icodec. This multicenter, open-label, treat-to-target study included 154 patients with A1c levels of 7-10% who were already receiving basal insulin daily and at least one oral glucose-lowering medication.

Patients were randomly assigned to one of three treatment approaches: a 100% loading dose of icodec (only the first dose was doubled), no loading dose, or once-daily glargine.

The primary endpoint was time in range (70-180 mg/dL) during weeks 15 and 16. This was achieved with 72.9% of patients receiving the icodec loading dose, 66.0% of patients receiving icodec without the loading dose, and 65.0% of patients receiving daily glargine. The difference between the icodec loading-dose method and glargine was significant, Dr. Bajaj and colleagues reported.

The mean A1c level was reduced from an overall average of 7.9% at baseline to 7.1% in the icodec loading dose group and to 7.4% in both the no-loading-dose and glargine groups.

Rates of adverse events and hypoglycemic episodes did not differ significantly among the groups.

Previous phase 2 data showing that the efficacy and safety of icodec were comparable with that of once-daily insulin glargine U100 in 247 insulin-naive patients with type 2 diabetes were published in November 2020 in the New England Journal of Medicine and were presented at the European Association for the Study of Diabetes (EASD) 2020 Annual Meeting, as reported by this news organization.

Both studies were funded by Novo Nordisk. Dr. Lingvey has received research funding, advisory/consulting fees, or other support from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Boehringer Ingelheim, Janssen, Intercept, Intarcia, Target RWE, Merck, Pfizer, Novartis, GI Dynamics, Mylan, Mannkind, Valeritas, Bayer, and Zealand Pharma. Dr. Bajaj has received speaking fees from AstraZeneca, Eli Lilly, Janssen Pharmaceuticals, Merck, and Novo Nordisk and research funding paid to LMC Healthcare for serving as principal investigator on clinical trials from Amgen, AstraZeneca Boehringer Ingelheim, Ceapro Inc, Eli Lilly, Gilead Sciences, Janssen Pharmaceuticals, Kowa Pharmaceuticals, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Sanofi, and Tricida.

A version of this article first appeared on Medscape.com.

Two new phase 2 studies show encouraging findings with the investigational once-weekly basal insulin analogue icodec (Novo Nordisk) for people with type 2 diabetes who require insulin.

Sara Freeman/MDedge News

Insulin icodec works by reversibly binding to albumin, which slows the release of the active insulin analogue. It has a half-life of about 1 week. The glucose-lowering effect is distributed nearly evenly over the course of that week.

Ildiko Lingvay, MD, of the University of Texas Southwestern Medical Center, Dallas, who is an author of both new articles, said: “A weekly insulin is a game changer that will decrease the treatment burden for patients while also improving compliance.”

She noted that these studies demonstrate optimal approaches to initiating treatment with icodec and serve “as the steppingstones for a large phase 3 clinical trial program that is currently ongoing ... which is designed to evaluate the efficacy of once-weekly insulin administration in patients with either type 1 or type 2 diabetes.”

Another advantage of the formulation, Dr. Lingvay pointed out in a press release from her institution, is that it could decrease the burden on caregivers of patients with diabetes who require insulin.

“For example, for patients who need help injecting, those living in long-term care facilities, and those with memory problems, a once-weekly insulin will facilitate treatment and decrease the burden on the care providers,” she explained.
 

Titration balances glycemic control with hypoglycemic risk reduction

The first phase 2 trial, published online April 19, 2021, in Diabetes Care, was an open-label, 16-week, treat-to-target study that involved 205 insulin-naive adults with type 2 diabetes whose hemoglobin A1c levels were 7%-10% while using oral glucose-lowering medications.

They were randomly assigned to one of three once-weekly icodec titration groups:

• Group A – Fasting glucose target of 80-130 mg/dL with adjustments ±21 units/wk
• Group B – Fasting glucose target of 80-130 mg/dL with ±28 units/wk
• Group C – Fasting glucose target of 70-108 mg/dL, adjusting by ±28 units/wk or to once-daily glargine U100 with a fasting glucose target of 80-130 mg/dL with adjustments of ±4 units/d

The percentage of time in the ideal glucose range of 70-180 mg/dL, assessed by continuous glucose monitoring during weeks 15-16, improved from baseline levels of 57.0%, 55.2%, 51.0% for groups A, B, and C, respectively, and from 55.3% for glargine to 76.6%, 83.0%, 80.9%, and 75.9%, respectively.

There were no unexpected safety problems. Hypoglycemia episodes of glucose levels <54 mg/dL occurred in 0.05, 0.15, 0.38, and 0.00 per patient-year for the four groups, respectively. None were severe (i.e., required assistance).

The titration for patients in group A (80-130 mg/dL, ±21 units/wk) yielded the best balance between glycemic control and risk for hypoglycemia, Dr. Lingvay and colleagues said.
 

Use of loading dose when switching to icodec improves time in range

In the other phase 2 trial, also published online April 19 in Diabetes Care, Harpreet S. Bajaj, MD, of Mount Sinai Hospital, Toronto, and colleagues, with Dr. Lingvay as a coauthor, examined two methods of switching to icodec. This multicenter, open-label, treat-to-target study included 154 patients with A1c levels of 7-10% who were already receiving basal insulin daily and at least one oral glucose-lowering medication.

Patients were randomly assigned to one of three treatment approaches: a 100% loading dose of icodec (only the first dose was doubled), no loading dose, or once-daily glargine.

The primary endpoint was time in range (70-180 mg/dL) during weeks 15 and 16. This was achieved with 72.9% of patients receiving the icodec loading dose, 66.0% of patients receiving icodec without the loading dose, and 65.0% of patients receiving daily glargine. The difference between the icodec loading-dose method and glargine was significant, Dr. Bajaj and colleagues reported.

The mean A1c level was reduced from an overall average of 7.9% at baseline to 7.1% in the icodec loading dose group and to 7.4% in both the no-loading-dose and glargine groups.

Rates of adverse events and hypoglycemic episodes did not differ significantly among the groups.

Previous phase 2 data showing that the efficacy and safety of icodec were comparable with that of once-daily insulin glargine U100 in 247 insulin-naive patients with type 2 diabetes were published in November 2020 in the New England Journal of Medicine and were presented at the European Association for the Study of Diabetes (EASD) 2020 Annual Meeting, as reported by this news organization.

Both studies were funded by Novo Nordisk. Dr. Lingvey has received research funding, advisory/consulting fees, or other support from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Boehringer Ingelheim, Janssen, Intercept, Intarcia, Target RWE, Merck, Pfizer, Novartis, GI Dynamics, Mylan, Mannkind, Valeritas, Bayer, and Zealand Pharma. Dr. Bajaj has received speaking fees from AstraZeneca, Eli Lilly, Janssen Pharmaceuticals, Merck, and Novo Nordisk and research funding paid to LMC Healthcare for serving as principal investigator on clinical trials from Amgen, AstraZeneca Boehringer Ingelheim, Ceapro Inc, Eli Lilly, Gilead Sciences, Janssen Pharmaceuticals, Kowa Pharmaceuticals, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Sanofi, and Tricida.

A version of this article first appeared on Medscape.com.