Dr. Lisa Carey, a breast cancer specialist from the University of North Carolina at Chapel Hill, looks at the latest data in metastatic breast cancer presented at the 2021 American Society of Clinical Oncology Annual Meeting.

First, Dr. Carey reviews an updated analysis from the PALOMA-3 trial of the CDK4/6 inhibitor palbociclib plus fulvestrant in women with HR+/HER2- advanced disease. This report showed that the observed survival benefit with the combination is maintained out to 6 years.

Next, she describes another updated survival analysis, this time from the MONALEESA-3 trial, which assessed fulvestrant plus another CDK4/6 inhibitor, ribociclib, in postmenopausal women with HR+/HER2- advanced disease. Again, the combination was associated with a survival benefit of almost 5 years, as well as a delay in subsequent chemotherapy.

Dr. Carey then reviews the Chinese sysucc-002 trial of endocrine therapy or chemotherapy added to trastuzumab in HR+/HER2+ disease. With noninferior outcomes and lower toxicity, trastuzumab plus endocrine therapy could become the preferred option and allow women to avoid chemotherapy.

She next turns to a subanalysis of the ASCENT trial, which examined sacituzumab govitecan in previously treated triple-negative disease. Even in the second-line metastatic setting, the drug showed a survival benefit.

Dr. Carey concludes by discussing a study that gathered patients’ views on treatment-related adverse effects, finding that over 90% would be willing to discuss alternative dosing options to improve their quality of life.

--

Jacobs Preyer Distinguished Professor, Breast Cancer Research, University of North Carolina at Chapel Hill; Deputy Director, Clinical Sciences, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina

Lisa A. Carey, MD, has disclosed the following relevant financial relationships:

Institution received research funding from: AbbVie; Immunomedics; NanoString Technologies; Novartis; Seattle Genetics; Syndax; Veracyte

Royalty-sharing agreement, investorship interest in licensed IP to startup company, Falcon Therapeutics, that is designing neural stem cell-based therapy for glioblastoma multiforme.

Other uncompensated relationships through institution: Aptitude Health; AstraZeneca/Daiichi Sankyo; Exact Sciences; G1 Therapeutics; Genentech/Roche; GlaxoSmithKline; Novartis; Sanofi.

Dr. Lisa Carey, a breast cancer specialist from the University of North Carolina at Chapel Hill, looks at the latest data in metastatic breast cancer presented at the 2021 American Society of Clinical Oncology Annual Meeting.

First, Dr. Carey reviews an updated analysis from the PALOMA-3 trial of the CDK4/6 inhibitor palbociclib plus fulvestrant in women with HR+/HER2- advanced disease. This report showed that the observed survival benefit with the combination is maintained out to 6 years.

Next, she describes another updated survival analysis, this time from the MONALEESA-3 trial, which assessed fulvestrant plus another CDK4/6 inhibitor, ribociclib, in postmenopausal women with HR+/HER2- advanced disease. Again, the combination was associated with a survival benefit of almost 5 years, as well as a delay in subsequent chemotherapy.

Dr. Carey then reviews the Chinese sysucc-002 trial of endocrine therapy or chemotherapy added to trastuzumab in HR+/HER2+ disease. With noninferior outcomes and lower toxicity, trastuzumab plus endocrine therapy could become the preferred option and allow women to avoid chemotherapy.

She next turns to a subanalysis of the ASCENT trial, which examined sacituzumab govitecan in previously treated triple-negative disease. Even in the second-line metastatic setting, the drug showed a survival benefit.

Dr. Carey concludes by discussing a study that gathered patients’ views on treatment-related adverse effects, finding that over 90% would be willing to discuss alternative dosing options to improve their quality of life.

--

Jacobs Preyer Distinguished Professor, Breast Cancer Research, University of North Carolina at Chapel Hill; Deputy Director, Clinical Sciences, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina

Lisa A. Carey, MD, has disclosed the following relevant financial relationships:

Institution received research funding from: AbbVie; Immunomedics; NanoString Technologies; Novartis; Seattle Genetics; Syndax; Veracyte

Royalty-sharing agreement, investorship interest in licensed IP to startup company, Falcon Therapeutics, that is designing neural stem cell-based therapy for glioblastoma multiforme.

Other uncompensated relationships through institution: Aptitude Health; AstraZeneca/Daiichi Sankyo; Exact Sciences; G1 Therapeutics; Genentech/Roche; GlaxoSmithKline; Novartis; Sanofi.

Dr. Lisa Carey, a breast cancer specialist from the University of North Carolina at Chapel Hill, looks at the latest data in metastatic breast cancer presented at the 2021 American Society of Clinical Oncology Annual Meeting.

First, Dr. Carey reviews an updated analysis from the PALOMA-3 trial of the CDK4/6 inhibitor palbociclib plus fulvestrant in women with HR+/HER2- advanced disease. This report showed that the observed survival benefit with the combination is maintained out to 6 years.

Next, she describes another updated survival analysis, this time from the MONALEESA-3 trial, which assessed fulvestrant plus another CDK4/6 inhibitor, ribociclib, in postmenopausal women with HR+/HER2- advanced disease. Again, the combination was associated with a survival benefit of almost 5 years, as well as a delay in subsequent chemotherapy.

Dr. Carey then reviews the Chinese sysucc-002 trial of endocrine therapy or chemotherapy added to trastuzumab in HR+/HER2+ disease. With noninferior outcomes and lower toxicity, trastuzumab plus endocrine therapy could become the preferred option and allow women to avoid chemotherapy.

She next turns to a subanalysis of the ASCENT trial, which examined sacituzumab govitecan in previously treated triple-negative disease. Even in the second-line metastatic setting, the drug showed a survival benefit.

Dr. Carey concludes by discussing a study that gathered patients’ views on treatment-related adverse effects, finding that over 90% would be willing to discuss alternative dosing options to improve their quality of life.

--

Jacobs Preyer Distinguished Professor, Breast Cancer Research, University of North Carolina at Chapel Hill; Deputy Director, Clinical Sciences, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina

Lisa A. Carey, MD, has disclosed the following relevant financial relationships:

Institution received research funding from: AbbVie; Immunomedics; NanoString Technologies; Novartis; Seattle Genetics; Syndax; Veracyte

Royalty-sharing agreement, investorship interest in licensed IP to startup company, Falcon Therapeutics, that is designing neural stem cell-based therapy for glioblastoma multiforme.

Other uncompensated relationships through institution: Aptitude Health; AstraZeneca/Daiichi Sankyo; Exact Sciences; G1 Therapeutics; Genentech/Roche; GlaxoSmithKline; Novartis; Sanofi.

Dr. Harold Burstein, breast cancer specialist from Dana-Farber Cancer Institute, discusses practice-changing research and advances in early-stage breast cancer from the 2021 American Society of Clinical Oncology Annual Meeting.

He first reports on OlympiA, a phase 3 trial of adjuvant olaparib after neoadjuvant chemotherapy in patients with BRCA1/2 mutations and high-risk HR+/HER2- disease. The results showed a substantial invasive and distant disease-free survival benefit and underscored the need for genetic testing for BRCA mutations in patients with early-stage disease.

Next, he discusses two studies in triple-negative breast cancer. EA1131 was a phase 3 postoperative trial of platinum-based chemotherapy vs capecitabine in patients with residual disease after neoadjuvant chemotherapy. The negative results suggested that additional chemotherapy does not improve outcomes.

In contrast, adding durvalumab to neoadjuvant chemotherapy significantly improved outcomes in GeparNuevo, calling into question whether the drug is needed in the later adjuvant setting.

Next, Dr. Burstein looks at the ADAPT-HR-/HER2+ trial of de-escalated neoadjuvant pertuzumab plus trastuzumab, which suggested that patients with early pathologic complete responses may be suitable for further de-escalation.

Finally, he reports on a retrospective analysis of more than 330,000 US individuals that puts the well-known financial toxicity associated with cancer care into numbers and shows the impact on people’s lives beyond their diagnosis.

--

Professor, Department of Medicine, Harvard Medical School

Institute Physician, Dana-Farber Cancer Institute, Boston, Massachusetts

Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships.

Dr. Harold Burstein, breast cancer specialist from Dana-Farber Cancer Institute, discusses practice-changing research and advances in early-stage breast cancer from the 2021 American Society of Clinical Oncology Annual Meeting.

He first reports on OlympiA, a phase 3 trial of adjuvant olaparib after neoadjuvant chemotherapy in patients with BRCA1/2 mutations and high-risk HR+/HER2- disease. The results showed a substantial invasive and distant disease-free survival benefit and underscored the need for genetic testing for BRCA mutations in patients with early-stage disease.

Next, he discusses two studies in triple-negative breast cancer. EA1131 was a phase 3 postoperative trial of platinum-based chemotherapy vs capecitabine in patients with residual disease after neoadjuvant chemotherapy. The negative results suggested that additional chemotherapy does not improve outcomes.

In contrast, adding durvalumab to neoadjuvant chemotherapy significantly improved outcomes in GeparNuevo, calling into question whether the drug is needed in the later adjuvant setting.

Next, Dr. Burstein looks at the ADAPT-HR-/HER2+ trial of de-escalated neoadjuvant pertuzumab plus trastuzumab, which suggested that patients with early pathologic complete responses may be suitable for further de-escalation.

Finally, he reports on a retrospective analysis of more than 330,000 US individuals that puts the well-known financial toxicity associated with cancer care into numbers and shows the impact on people’s lives beyond their diagnosis.

--

Professor, Department of Medicine, Harvard Medical School

Institute Physician, Dana-Farber Cancer Institute, Boston, Massachusetts

Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships.

Dr. Harold Burstein, breast cancer specialist from Dana-Farber Cancer Institute, discusses practice-changing research and advances in early-stage breast cancer from the 2021 American Society of Clinical Oncology Annual Meeting.

He first reports on OlympiA, a phase 3 trial of adjuvant olaparib after neoadjuvant chemotherapy in patients with BRCA1/2 mutations and high-risk HR+/HER2- disease. The results showed a substantial invasive and distant disease-free survival benefit and underscored the need for genetic testing for BRCA mutations in patients with early-stage disease.

Next, he discusses two studies in triple-negative breast cancer. EA1131 was a phase 3 postoperative trial of platinum-based chemotherapy vs capecitabine in patients with residual disease after neoadjuvant chemotherapy. The negative results suggested that additional chemotherapy does not improve outcomes.

In contrast, adding durvalumab to neoadjuvant chemotherapy significantly improved outcomes in GeparNuevo, calling into question whether the drug is needed in the later adjuvant setting.

Next, Dr. Burstein looks at the ADAPT-HR-/HER2+ trial of de-escalated neoadjuvant pertuzumab plus trastuzumab, which suggested that patients with early pathologic complete responses may be suitable for further de-escalation.

Finally, he reports on a retrospective analysis of more than 330,000 US individuals that puts the well-known financial toxicity associated with cancer care into numbers and shows the impact on people’s lives beyond their diagnosis.

--

Professor, Department of Medicine, Harvard Medical School

Institute Physician, Dana-Farber Cancer Institute, Boston, Massachusetts

Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships.

Insulet’s investigational Omnipod 5 automated insulin delivery system improves glycemic control in people with type 1 diabetes aged as young as 2 years, new data suggest.

The Omnipod 5 system combines a tubing-free insulin-filled delivery “Pod” with the Dexcom G6 continuous glucose monitor and an algorithm built into the Pod connecting the two devices via a smartphone app to semiautomate insulin delivery. It is currently under review by the Food and Drug Administration. The company expects to launch it in limited release during the second half of 2021. 

Results from a pivotal trial of the system in children aged 2-5.9 years with type 1 diabetes were presented during the annual scientific sessions of the American Diabetes Association.

Follow-up data at 6 months were also presented for another pivotal study of 112 children aged 6-13.9 years and 129 adults aged 14-70 years. Those primary 3-month data were reported earlier this year at the Endocrine Society’s annual meeting and subsequently published online June 7, 2021, in Diabetes Care. Another study presented at ADA looked at quality of life in children using Omnipod 5 and their caregivers. 

If approved by the FDA, the Omnipod 5 would be the third commercially available automated insulin delivery system – also called hybrid closed-loop or artificial pancreas systems – in the United States. It would be the second approved for children as young as 2 years of age and the first to deliver insulin subcutaneously without tubing.
 

‘No-tubing’ feature will be a draw for parents of young children

Asked to comment, pediatric endocrinologist Laura M. Jacobsen, MD, of the University of Florida, Gainesville, said in an interview: “I think the big advantage for the Omnipod 5 is that [if approved it will be] the only tubeless automated insulin delivery system in the U.S.”

“The automated delivery systems have just been wonderful for helping patients achieve time in range, especially overnight. And the fact that this goes down to such a young age where that can be very difficult is wonderful.”

Another difference between the Omnipod 5 and other systems is the ability to adjust glucose targets (from 110 to 150 mg/dL), although newer versions of the currently available hybrid closed-loop systems are expected to include that feature as well. “They’re all slightly different in the way the algorithms work, but I think the end result is similar,” Dr. Jacobsen said.

But, she said, the no-tubing feature might be particularly helpful for some very active young kids. “A lot of small kids do use the tubed pumps, and you can make it work with a lot of kids, but with some kids it just won’t ... the tubing gets caught. I think this really helps parents make the step. A lot of them don’t want to try the tubing whereas they see the Omnipod and might feel a little more confidence to try a pump.”

Overall, said Dr. Jacobsen, who has no financial disclosures with Insulet, Dexcom, or any of their competitors, “I think any addition to the technology field to improve quality of life for people with type 1 diabetes is important and people need choices.”
 

Pivotal data show benefit in ‘difficult-to-manage’ preschool children

Pivotal 3-month data for the Omnipod 5 in children aged 2-5.9 years with type 1 diabetes were presented on June 26 by pediatric endocrinologist Jennifer Sherr, MD, PhD, Yale University, New Haven, Conn.

“As a pediatric endocrinologist, I can attest to the difficulty of managing this age group, due to grazing eating patterns and erratic physical activity. Oftentimes, care providers may fear hypoglycemia as these youth can not verbalize or self-treat lows,” she remarked.

A total of 80 children were enrolled at 10 institutions across the United Sates. There was a single 14-day standard therapy phase (baseline), followed by 3 months of automated insulin delivery during which the children’s eating and exercise were unrestricted.

At 3 months, average hemoglobin A1c had fallen from 7.4% at baseline to 6.9%, a significant difference (P < .05). The proportions achieving the target A1c of less than 7% were 54% at 3 months versus 31% at baseline. The reduction was even greater among the 25 with baseline A1c of 8% or greater, although it was significant even among the 55 who started with a lower A1c (–1.06 vs. –0.31 percentage points; both P < .05). 

Time in range rose from 57.2% at baseline to 68.1% at 3 months (P < .05).

“These youngsters are spending an average of 2.6 more hours/day in range,” Dr. Sherr commented, noting that the difference became apparent shortly after study start and was maintained during the 3 months.

Dr. Sherr noted that this 10.9% improvement in time in range with Omnipod 5 was similar to improvements in the previously reported pivotal study of older children and adults. Data from that study showed improvement in time in range from a gain of 15.6% for the 6 to 13.9 year olds to 8.0% for those aged 26-49 years. Interestingly, improvements in time in range were seen even in the oldest group, aged 50-70, who increased from an already high baseline of 69.9% to 79.1% with Omnipod 5 after 3 months.

In her current study, in the youngest age group, the improvement in time in range was achieved primarily by a reduction of time above range, from 2.4 fewer hours/day above 180 mg/dL, while time below 70 mg/dL was reduced by 4 minutes/day. Overnight time in range improved by 1.4 hours/night, with most of the improvements in reduction of hyperglycemia.

The proportions meeting the combined goals of less than 4% time below range and greater than 60% time in range rose from 29% to 65%.

There were no episodes of severe hypoglycemia or diabetic ketoacidosis during the 3-month study phase.

Another important related metric, sleep quality for parents/caregivers, also improved. The percentage reporting overall sleep quality of “very good” or “fairly good” increased from 65% at baseline to 90% with Omnipod 5, while “very bad” sleep quality fell from 8.8% to 0%.

All 80 patients completed the study and elected to continue in a 12-month extension phase.
 

Ongoing benefit seen in older children and adults

In a late-breaking poster presented on June 25, Anders L. Carlson, MD, medical director at the International Diabetes Center at Park Nicollet, Minneapolis, presented more follow-up data to the previously reported 3-month pivotal study, including 108 older children and 109 adults from the original study.

A1c remained lower after 6 months than at baseline for both children and adults (P < .001). In the children, A1c levels weren’t significantly different at the end of 6 versus 3 months, while in the adults there was an additional 0.1 percentage point decrease (P < .01).

There was one episode of diabetic ketoacidosis and no severe hypoglycemic episodes in the 3-month extension. “Sustained reduction of A1c indicates the potential long-term benefit of the Omnipod 5 System,” Dr. Carlson and colleagues concluded.
 

Reduced diabetes distress, don’t forget parents’ quality of life

Meanwhile, psychologist Korey K. Hood, PhD, of Stanford (Calif.) University, presented quality of life data at the meeting for 83 children aged 6-11.9 years and 42 teens aged 12-17.9 years using the Omnipod 5 from the larger study population and their parents.

Significant improvements were seen for both the youth and their caregivers in the Problem Areas in Diabetes score, a measure of diabetes-related emotional distress. Changes were less dramatic on the Hypoglycemic Confidence Scale, although improvements were significant for the caregivers of the younger children.

“We know this is a group that is really worried about hypoglycemia across a lot of situations, not just sleep but also school and outside of the home. So, to increase their confidence to this extent I think is a pretty important finding,” Dr. Hood commented.

There were nonsignificant trends in improvement across groups on the Pittsburgh Sleep Quality Index, but overall sleep quality did significantly improve among parents of the younger children. And on the World Health Organization–5 quality of life survey, significant improvements again were seen among the caregivers of young children.

“Reduced diabetes distress and improved quality of life are key benefits of using the Omnipod 5 [automated insulin delivery] system that are complementary to the glycemic benefits achieved,” Dr. Hood said.

Dr. Jacobsen has reported no relevant financial relationships. Dr. Sherr has reported being an adviser for, consultant for, and/or grant recipient from Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, Eli Lilly, Lexicon, Sanofi, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Hood has reported being a consultant for Cecelia Health, Havas, and Cercacor.

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

Insulet’s investigational Omnipod 5 automated insulin delivery system improves glycemic control in people with type 1 diabetes aged as young as 2 years, new data suggest.

The Omnipod 5 system combines a tubing-free insulin-filled delivery “Pod” with the Dexcom G6 continuous glucose monitor and an algorithm built into the Pod connecting the two devices via a smartphone app to semiautomate insulin delivery. It is currently under review by the Food and Drug Administration. The company expects to launch it in limited release during the second half of 2021. 

Results from a pivotal trial of the system in children aged 2-5.9 years with type 1 diabetes were presented during the annual scientific sessions of the American Diabetes Association.

Follow-up data at 6 months were also presented for another pivotal study of 112 children aged 6-13.9 years and 129 adults aged 14-70 years. Those primary 3-month data were reported earlier this year at the Endocrine Society’s annual meeting and subsequently published online June 7, 2021, in Diabetes Care. Another study presented at ADA looked at quality of life in children using Omnipod 5 and their caregivers. 

If approved by the FDA, the Omnipod 5 would be the third commercially available automated insulin delivery system – also called hybrid closed-loop or artificial pancreas systems – in the United States. It would be the second approved for children as young as 2 years of age and the first to deliver insulin subcutaneously without tubing.
 

‘No-tubing’ feature will be a draw for parents of young children

Asked to comment, pediatric endocrinologist Laura M. Jacobsen, MD, of the University of Florida, Gainesville, said in an interview: “I think the big advantage for the Omnipod 5 is that [if approved it will be] the only tubeless automated insulin delivery system in the U.S.”

“The automated delivery systems have just been wonderful for helping patients achieve time in range, especially overnight. And the fact that this goes down to such a young age where that can be very difficult is wonderful.”

Another difference between the Omnipod 5 and other systems is the ability to adjust glucose targets (from 110 to 150 mg/dL), although newer versions of the currently available hybrid closed-loop systems are expected to include that feature as well. “They’re all slightly different in the way the algorithms work, but I think the end result is similar,” Dr. Jacobsen said.

But, she said, the no-tubing feature might be particularly helpful for some very active young kids. “A lot of small kids do use the tubed pumps, and you can make it work with a lot of kids, but with some kids it just won’t ... the tubing gets caught. I think this really helps parents make the step. A lot of them don’t want to try the tubing whereas they see the Omnipod and might feel a little more confidence to try a pump.”

Overall, said Dr. Jacobsen, who has no financial disclosures with Insulet, Dexcom, or any of their competitors, “I think any addition to the technology field to improve quality of life for people with type 1 diabetes is important and people need choices.”
 

Pivotal data show benefit in ‘difficult-to-manage’ preschool children

Pivotal 3-month data for the Omnipod 5 in children aged 2-5.9 years with type 1 diabetes were presented on June 26 by pediatric endocrinologist Jennifer Sherr, MD, PhD, Yale University, New Haven, Conn.

“As a pediatric endocrinologist, I can attest to the difficulty of managing this age group, due to grazing eating patterns and erratic physical activity. Oftentimes, care providers may fear hypoglycemia as these youth can not verbalize or self-treat lows,” she remarked.

A total of 80 children were enrolled at 10 institutions across the United Sates. There was a single 14-day standard therapy phase (baseline), followed by 3 months of automated insulin delivery during which the children’s eating and exercise were unrestricted.

At 3 months, average hemoglobin A1c had fallen from 7.4% at baseline to 6.9%, a significant difference (P < .05). The proportions achieving the target A1c of less than 7% were 54% at 3 months versus 31% at baseline. The reduction was even greater among the 25 with baseline A1c of 8% or greater, although it was significant even among the 55 who started with a lower A1c (–1.06 vs. –0.31 percentage points; both P < .05). 

Time in range rose from 57.2% at baseline to 68.1% at 3 months (P < .05).

“These youngsters are spending an average of 2.6 more hours/day in range,” Dr. Sherr commented, noting that the difference became apparent shortly after study start and was maintained during the 3 months.

Dr. Sherr noted that this 10.9% improvement in time in range with Omnipod 5 was similar to improvements in the previously reported pivotal study of older children and adults. Data from that study showed improvement in time in range from a gain of 15.6% for the 6 to 13.9 year olds to 8.0% for those aged 26-49 years. Interestingly, improvements in time in range were seen even in the oldest group, aged 50-70, who increased from an already high baseline of 69.9% to 79.1% with Omnipod 5 after 3 months.

In her current study, in the youngest age group, the improvement in time in range was achieved primarily by a reduction of time above range, from 2.4 fewer hours/day above 180 mg/dL, while time below 70 mg/dL was reduced by 4 minutes/day. Overnight time in range improved by 1.4 hours/night, with most of the improvements in reduction of hyperglycemia.

The proportions meeting the combined goals of less than 4% time below range and greater than 60% time in range rose from 29% to 65%.

There were no episodes of severe hypoglycemia or diabetic ketoacidosis during the 3-month study phase.

Another important related metric, sleep quality for parents/caregivers, also improved. The percentage reporting overall sleep quality of “very good” or “fairly good” increased from 65% at baseline to 90% with Omnipod 5, while “very bad” sleep quality fell from 8.8% to 0%.

All 80 patients completed the study and elected to continue in a 12-month extension phase.
 

Ongoing benefit seen in older children and adults

In a late-breaking poster presented on June 25, Anders L. Carlson, MD, medical director at the International Diabetes Center at Park Nicollet, Minneapolis, presented more follow-up data to the previously reported 3-month pivotal study, including 108 older children and 109 adults from the original study.

A1c remained lower after 6 months than at baseline for both children and adults (P < .001). In the children, A1c levels weren’t significantly different at the end of 6 versus 3 months, while in the adults there was an additional 0.1 percentage point decrease (P < .01).

There was one episode of diabetic ketoacidosis and no severe hypoglycemic episodes in the 3-month extension. “Sustained reduction of A1c indicates the potential long-term benefit of the Omnipod 5 System,” Dr. Carlson and colleagues concluded.
 

Reduced diabetes distress, don’t forget parents’ quality of life

Meanwhile, psychologist Korey K. Hood, PhD, of Stanford (Calif.) University, presented quality of life data at the meeting for 83 children aged 6-11.9 years and 42 teens aged 12-17.9 years using the Omnipod 5 from the larger study population and their parents.

Significant improvements were seen for both the youth and their caregivers in the Problem Areas in Diabetes score, a measure of diabetes-related emotional distress. Changes were less dramatic on the Hypoglycemic Confidence Scale, although improvements were significant for the caregivers of the younger children.

“We know this is a group that is really worried about hypoglycemia across a lot of situations, not just sleep but also school and outside of the home. So, to increase their confidence to this extent I think is a pretty important finding,” Dr. Hood commented.

There were nonsignificant trends in improvement across groups on the Pittsburgh Sleep Quality Index, but overall sleep quality did significantly improve among parents of the younger children. And on the World Health Organization–5 quality of life survey, significant improvements again were seen among the caregivers of young children.

“Reduced diabetes distress and improved quality of life are key benefits of using the Omnipod 5 [automated insulin delivery] system that are complementary to the glycemic benefits achieved,” Dr. Hood said.

Dr. Jacobsen has reported no relevant financial relationships. Dr. Sherr has reported being an adviser for, consultant for, and/or grant recipient from Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, Eli Lilly, Lexicon, Sanofi, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Hood has reported being a consultant for Cecelia Health, Havas, and Cercacor.

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

Insulet’s investigational Omnipod 5 automated insulin delivery system improves glycemic control in people with type 1 diabetes aged as young as 2 years, new data suggest.

The Omnipod 5 system combines a tubing-free insulin-filled delivery “Pod” with the Dexcom G6 continuous glucose monitor and an algorithm built into the Pod connecting the two devices via a smartphone app to semiautomate insulin delivery. It is currently under review by the Food and Drug Administration. The company expects to launch it in limited release during the second half of 2021. 

Results from a pivotal trial of the system in children aged 2-5.9 years with type 1 diabetes were presented during the annual scientific sessions of the American Diabetes Association.

Follow-up data at 6 months were also presented for another pivotal study of 112 children aged 6-13.9 years and 129 adults aged 14-70 years. Those primary 3-month data were reported earlier this year at the Endocrine Society’s annual meeting and subsequently published online June 7, 2021, in Diabetes Care. Another study presented at ADA looked at quality of life in children using Omnipod 5 and their caregivers. 

If approved by the FDA, the Omnipod 5 would be the third commercially available automated insulin delivery system – also called hybrid closed-loop or artificial pancreas systems – in the United States. It would be the second approved for children as young as 2 years of age and the first to deliver insulin subcutaneously without tubing.
 

‘No-tubing’ feature will be a draw for parents of young children

Asked to comment, pediatric endocrinologist Laura M. Jacobsen, MD, of the University of Florida, Gainesville, said in an interview: “I think the big advantage for the Omnipod 5 is that [if approved it will be] the only tubeless automated insulin delivery system in the U.S.”

“The automated delivery systems have just been wonderful for helping patients achieve time in range, especially overnight. And the fact that this goes down to such a young age where that can be very difficult is wonderful.”

Another difference between the Omnipod 5 and other systems is the ability to adjust glucose targets (from 110 to 150 mg/dL), although newer versions of the currently available hybrid closed-loop systems are expected to include that feature as well. “They’re all slightly different in the way the algorithms work, but I think the end result is similar,” Dr. Jacobsen said.

But, she said, the no-tubing feature might be particularly helpful for some very active young kids. “A lot of small kids do use the tubed pumps, and you can make it work with a lot of kids, but with some kids it just won’t ... the tubing gets caught. I think this really helps parents make the step. A lot of them don’t want to try the tubing whereas they see the Omnipod and might feel a little more confidence to try a pump.”

Overall, said Dr. Jacobsen, who has no financial disclosures with Insulet, Dexcom, or any of their competitors, “I think any addition to the technology field to improve quality of life for people with type 1 diabetes is important and people need choices.”
 

Pivotal data show benefit in ‘difficult-to-manage’ preschool children

Pivotal 3-month data for the Omnipod 5 in children aged 2-5.9 years with type 1 diabetes were presented on June 26 by pediatric endocrinologist Jennifer Sherr, MD, PhD, Yale University, New Haven, Conn.

“As a pediatric endocrinologist, I can attest to the difficulty of managing this age group, due to grazing eating patterns and erratic physical activity. Oftentimes, care providers may fear hypoglycemia as these youth can not verbalize or self-treat lows,” she remarked.

A total of 80 children were enrolled at 10 institutions across the United Sates. There was a single 14-day standard therapy phase (baseline), followed by 3 months of automated insulin delivery during which the children’s eating and exercise were unrestricted.

At 3 months, average hemoglobin A1c had fallen from 7.4% at baseline to 6.9%, a significant difference (P < .05). The proportions achieving the target A1c of less than 7% were 54% at 3 months versus 31% at baseline. The reduction was even greater among the 25 with baseline A1c of 8% or greater, although it was significant even among the 55 who started with a lower A1c (–1.06 vs. –0.31 percentage points; both P < .05). 

Time in range rose from 57.2% at baseline to 68.1% at 3 months (P < .05).

“These youngsters are spending an average of 2.6 more hours/day in range,” Dr. Sherr commented, noting that the difference became apparent shortly after study start and was maintained during the 3 months.

Dr. Sherr noted that this 10.9% improvement in time in range with Omnipod 5 was similar to improvements in the previously reported pivotal study of older children and adults. Data from that study showed improvement in time in range from a gain of 15.6% for the 6 to 13.9 year olds to 8.0% for those aged 26-49 years. Interestingly, improvements in time in range were seen even in the oldest group, aged 50-70, who increased from an already high baseline of 69.9% to 79.1% with Omnipod 5 after 3 months.

In her current study, in the youngest age group, the improvement in time in range was achieved primarily by a reduction of time above range, from 2.4 fewer hours/day above 180 mg/dL, while time below 70 mg/dL was reduced by 4 minutes/day. Overnight time in range improved by 1.4 hours/night, with most of the improvements in reduction of hyperglycemia.

The proportions meeting the combined goals of less than 4% time below range and greater than 60% time in range rose from 29% to 65%.

There were no episodes of severe hypoglycemia or diabetic ketoacidosis during the 3-month study phase.

Another important related metric, sleep quality for parents/caregivers, also improved. The percentage reporting overall sleep quality of “very good” or “fairly good” increased from 65% at baseline to 90% with Omnipod 5, while “very bad” sleep quality fell from 8.8% to 0%.

All 80 patients completed the study and elected to continue in a 12-month extension phase.
 

Ongoing benefit seen in older children and adults

In a late-breaking poster presented on June 25, Anders L. Carlson, MD, medical director at the International Diabetes Center at Park Nicollet, Minneapolis, presented more follow-up data to the previously reported 3-month pivotal study, including 108 older children and 109 adults from the original study.

A1c remained lower after 6 months than at baseline for both children and adults (P < .001). In the children, A1c levels weren’t significantly different at the end of 6 versus 3 months, while in the adults there was an additional 0.1 percentage point decrease (P < .01).

There was one episode of diabetic ketoacidosis and no severe hypoglycemic episodes in the 3-month extension. “Sustained reduction of A1c indicates the potential long-term benefit of the Omnipod 5 System,” Dr. Carlson and colleagues concluded.
 

Reduced diabetes distress, don’t forget parents’ quality of life

Meanwhile, psychologist Korey K. Hood, PhD, of Stanford (Calif.) University, presented quality of life data at the meeting for 83 children aged 6-11.9 years and 42 teens aged 12-17.9 years using the Omnipod 5 from the larger study population and their parents.

Significant improvements were seen for both the youth and their caregivers in the Problem Areas in Diabetes score, a measure of diabetes-related emotional distress. Changes were less dramatic on the Hypoglycemic Confidence Scale, although improvements were significant for the caregivers of the younger children.

“We know this is a group that is really worried about hypoglycemia across a lot of situations, not just sleep but also school and outside of the home. So, to increase their confidence to this extent I think is a pretty important finding,” Dr. Hood commented.

There were nonsignificant trends in improvement across groups on the Pittsburgh Sleep Quality Index, but overall sleep quality did significantly improve among parents of the younger children. And on the World Health Organization–5 quality of life survey, significant improvements again were seen among the caregivers of young children.

“Reduced diabetes distress and improved quality of life are key benefits of using the Omnipod 5 [automated insulin delivery] system that are complementary to the glycemic benefits achieved,” Dr. Hood said.

Dr. Jacobsen has reported no relevant financial relationships. Dr. Sherr has reported being an adviser for, consultant for, and/or grant recipient from Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, Eli Lilly, Lexicon, Sanofi, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Hood has reported being a consultant for Cecelia Health, Havas, and Cercacor.

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

For racial or ethnic minority youths with type 1 diabetes, participating in an interventional program improves access to care, new research shows.

Youth categorized as Black, Indigenous, and other people of color (BIPOC) had significantly improved outpatient attendance during and after participating in Novel Interventions in Children’s Healthcare (NICH), a systems intervention for children with chronic health conditions and their families.

By comparison, no improvements in care access were observed among BIPOC children who were not able to access the program because of insurance or other reasons, David V. Wagner, PhD, Associate Professor and NICH research director at Oregon Health & Science University, Portland, reported at the annual scientific sessions of the American Diabetes Association.

The findings demonstrate a need for intensive, home-based services that aim to correct health inequities, said Dr. Wagner, who presented the findings along with Winniebhelle Cadiz, a scholar in the BUILD EXITO undergraduate research training program at Portland (Ore.) State University.

The NICH program hinges on trained interventionists who visit families at home, attend clinic visits, and work with schools and other contacts to help solve problems that keep children from following medical instructions, according to a program description.

“Families report having somebody by their side to help them navigate the system, address the transportation difficulties experienced, and help them and build that relationship with their health care provider seems to be hugely influential in terms of helping them navigate and access care,” Dr. Wagner said in a presentation of the study.
 

A NICH for youths with chronic health conditions

The NICH program differs from some other programs that have been developed in an attempt to improve health outcomes among youths in the community, according to Dr. Wagner.

“Many of the programs that exist out there are often piloted on, and seemingly built for, those who have more resources,” he said in his presentation. “Those who are in greatest need often have difficulty accessing and responding to the services.”

NICH doesn’t take the place of existing services, but is “an addition to the continuum of care” for youths and families who are struggling because of lack of resources or marginalization in the health care system, Dr. Wagner said.

While NICH is not specific to any one chronic health condition, several previous investigations have specifically looked at the impact of the NICH program on access to care in youths with type 1 diabetes.

Youths participating in the program for a year had fewer ED visits, including fewer visits with diabetic ketoacidosis (DKA), as well as fewer and shorter admissions as compared with the year prior to participating in the program, Dr. Wagner said.

In another study, youths had fewer admissions for diabetes or DKA and less frequent pediatric ICU contact during the NICH program, as compared with before the program.

Another study showed that, while NICH had no impact overall on access to care among youths with type 1 diabetes, BIPOC youths had an improvement in the mean number of outpatient visits as compared with preprogram levels. However, because none of those studies included a control group, Dr. Wagner said, it remained unclear whether this systems intervention might improve outpatient access among youths with type 1 diabetes as compared with those who did not participate.
 

Intervention linked to increased BIPOC care access

The latest study includes 144 youths with type 1 diabetes referred for the program. The mean age was 13.7 years, 58% were female, and 81% were non-Hispanic White. While 51 youths were able to participate in NICH, the remaining 93 were not served by the program because of insurance denial or nonresponse, according to investigators.

While participation in the program made no difference in access to care overall, results of this study suggest NICH reduced access disparities among BIPOC youths, the investigators said.

Those BIPOC youth, 28 in total, had significantly worse access to care prior to referral. However, BIPOC youth participation in NICH was associated with improved attendance at endocrinology appointments and outpatient attendance overall.

A mean change of 1.9 more appointments per year was seen among BIPOC youth who participated in NICH, compared with a mean decrease of 0.5 appointments per year among BIPOC youth not served by the program (P = .03), according to the study abstract.

Prior to NICH participation, outpatient attendance among BIPOC youths was about 2.5 visits per year, data presented by the investigators show.
 

Systemic changes needed

This study is representative of systemic changes that are needed to improve access to quality care for BIPOC youth, according Cynthia E. Muñoz, PhD, MPH, ADA’s president of health care and education.

“We know that there are increased risks for poor health outcomes for these children and youths, and we know that there is a risk for mental health and psychosocial challenges for youth from these communities,” said Dr. Muñoz, a bilingual licensed psychologist and assistant professor of clinical pediatrics at the University of Southern California, Los Angeles.

In his presentation, Dr. Wagner said lumping racial and ethnic minority participants under a single BIPOC header probably wasn’t ideal because of the diversity and differences among racial and ethnic minorities. However, it was necessary in this particular study because of limited sample size.

Dr. Wagner and coauthors disclosed no conflicts of interest related to the research, which was supported by the Leona M. and Harry B. Helmsley Charitable Trust.

For racial or ethnic minority youths with type 1 diabetes, participating in an interventional program improves access to care, new research shows.

Youth categorized as Black, Indigenous, and other people of color (BIPOC) had significantly improved outpatient attendance during and after participating in Novel Interventions in Children’s Healthcare (NICH), a systems intervention for children with chronic health conditions and their families.

By comparison, no improvements in care access were observed among BIPOC children who were not able to access the program because of insurance or other reasons, David V. Wagner, PhD, Associate Professor and NICH research director at Oregon Health & Science University, Portland, reported at the annual scientific sessions of the American Diabetes Association.

The findings demonstrate a need for intensive, home-based services that aim to correct health inequities, said Dr. Wagner, who presented the findings along with Winniebhelle Cadiz, a scholar in the BUILD EXITO undergraduate research training program at Portland (Ore.) State University.

The NICH program hinges on trained interventionists who visit families at home, attend clinic visits, and work with schools and other contacts to help solve problems that keep children from following medical instructions, according to a program description.

“Families report having somebody by their side to help them navigate the system, address the transportation difficulties experienced, and help them and build that relationship with their health care provider seems to be hugely influential in terms of helping them navigate and access care,” Dr. Wagner said in a presentation of the study.
 

A NICH for youths with chronic health conditions

The NICH program differs from some other programs that have been developed in an attempt to improve health outcomes among youths in the community, according to Dr. Wagner.

“Many of the programs that exist out there are often piloted on, and seemingly built for, those who have more resources,” he said in his presentation. “Those who are in greatest need often have difficulty accessing and responding to the services.”

NICH doesn’t take the place of existing services, but is “an addition to the continuum of care” for youths and families who are struggling because of lack of resources or marginalization in the health care system, Dr. Wagner said.

While NICH is not specific to any one chronic health condition, several previous investigations have specifically looked at the impact of the NICH program on access to care in youths with type 1 diabetes.

Youths participating in the program for a year had fewer ED visits, including fewer visits with diabetic ketoacidosis (DKA), as well as fewer and shorter admissions as compared with the year prior to participating in the program, Dr. Wagner said.

In another study, youths had fewer admissions for diabetes or DKA and less frequent pediatric ICU contact during the NICH program, as compared with before the program.

Another study showed that, while NICH had no impact overall on access to care among youths with type 1 diabetes, BIPOC youths had an improvement in the mean number of outpatient visits as compared with preprogram levels. However, because none of those studies included a control group, Dr. Wagner said, it remained unclear whether this systems intervention might improve outpatient access among youths with type 1 diabetes as compared with those who did not participate.
 

Intervention linked to increased BIPOC care access

The latest study includes 144 youths with type 1 diabetes referred for the program. The mean age was 13.7 years, 58% were female, and 81% were non-Hispanic White. While 51 youths were able to participate in NICH, the remaining 93 were not served by the program because of insurance denial or nonresponse, according to investigators.

While participation in the program made no difference in access to care overall, results of this study suggest NICH reduced access disparities among BIPOC youths, the investigators said.

Those BIPOC youth, 28 in total, had significantly worse access to care prior to referral. However, BIPOC youth participation in NICH was associated with improved attendance at endocrinology appointments and outpatient attendance overall.

A mean change of 1.9 more appointments per year was seen among BIPOC youth who participated in NICH, compared with a mean decrease of 0.5 appointments per year among BIPOC youth not served by the program (P = .03), according to the study abstract.

Prior to NICH participation, outpatient attendance among BIPOC youths was about 2.5 visits per year, data presented by the investigators show.
 

Systemic changes needed

This study is representative of systemic changes that are needed to improve access to quality care for BIPOC youth, according Cynthia E. Muñoz, PhD, MPH, ADA’s president of health care and education.

“We know that there are increased risks for poor health outcomes for these children and youths, and we know that there is a risk for mental health and psychosocial challenges for youth from these communities,” said Dr. Muñoz, a bilingual licensed psychologist and assistant professor of clinical pediatrics at the University of Southern California, Los Angeles.

In his presentation, Dr. Wagner said lumping racial and ethnic minority participants under a single BIPOC header probably wasn’t ideal because of the diversity and differences among racial and ethnic minorities. However, it was necessary in this particular study because of limited sample size.

Dr. Wagner and coauthors disclosed no conflicts of interest related to the research, which was supported by the Leona M. and Harry B. Helmsley Charitable Trust.

For racial or ethnic minority youths with type 1 diabetes, participating in an interventional program improves access to care, new research shows.

Youth categorized as Black, Indigenous, and other people of color (BIPOC) had significantly improved outpatient attendance during and after participating in Novel Interventions in Children’s Healthcare (NICH), a systems intervention for children with chronic health conditions and their families.

By comparison, no improvements in care access were observed among BIPOC children who were not able to access the program because of insurance or other reasons, David V. Wagner, PhD, Associate Professor and NICH research director at Oregon Health & Science University, Portland, reported at the annual scientific sessions of the American Diabetes Association.

The findings demonstrate a need for intensive, home-based services that aim to correct health inequities, said Dr. Wagner, who presented the findings along with Winniebhelle Cadiz, a scholar in the BUILD EXITO undergraduate research training program at Portland (Ore.) State University.

The NICH program hinges on trained interventionists who visit families at home, attend clinic visits, and work with schools and other contacts to help solve problems that keep children from following medical instructions, according to a program description.

“Families report having somebody by their side to help them navigate the system, address the transportation difficulties experienced, and help them and build that relationship with their health care provider seems to be hugely influential in terms of helping them navigate and access care,” Dr. Wagner said in a presentation of the study.
 

A NICH for youths with chronic health conditions

The NICH program differs from some other programs that have been developed in an attempt to improve health outcomes among youths in the community, according to Dr. Wagner.

“Many of the programs that exist out there are often piloted on, and seemingly built for, those who have more resources,” he said in his presentation. “Those who are in greatest need often have difficulty accessing and responding to the services.”

NICH doesn’t take the place of existing services, but is “an addition to the continuum of care” for youths and families who are struggling because of lack of resources or marginalization in the health care system, Dr. Wagner said.

While NICH is not specific to any one chronic health condition, several previous investigations have specifically looked at the impact of the NICH program on access to care in youths with type 1 diabetes.

Youths participating in the program for a year had fewer ED visits, including fewer visits with diabetic ketoacidosis (DKA), as well as fewer and shorter admissions as compared with the year prior to participating in the program, Dr. Wagner said.

In another study, youths had fewer admissions for diabetes or DKA and less frequent pediatric ICU contact during the NICH program, as compared with before the program.

Another study showed that, while NICH had no impact overall on access to care among youths with type 1 diabetes, BIPOC youths had an improvement in the mean number of outpatient visits as compared with preprogram levels. However, because none of those studies included a control group, Dr. Wagner said, it remained unclear whether this systems intervention might improve outpatient access among youths with type 1 diabetes as compared with those who did not participate.
 

Intervention linked to increased BIPOC care access

The latest study includes 144 youths with type 1 diabetes referred for the program. The mean age was 13.7 years, 58% were female, and 81% were non-Hispanic White. While 51 youths were able to participate in NICH, the remaining 93 were not served by the program because of insurance denial or nonresponse, according to investigators.

While participation in the program made no difference in access to care overall, results of this study suggest NICH reduced access disparities among BIPOC youths, the investigators said.

Those BIPOC youth, 28 in total, had significantly worse access to care prior to referral. However, BIPOC youth participation in NICH was associated with improved attendance at endocrinology appointments and outpatient attendance overall.

A mean change of 1.9 more appointments per year was seen among BIPOC youth who participated in NICH, compared with a mean decrease of 0.5 appointments per year among BIPOC youth not served by the program (P = .03), according to the study abstract.

Prior to NICH participation, outpatient attendance among BIPOC youths was about 2.5 visits per year, data presented by the investigators show.
 

Systemic changes needed

This study is representative of systemic changes that are needed to improve access to quality care for BIPOC youth, according Cynthia E. Muñoz, PhD, MPH, ADA’s president of health care and education.

“We know that there are increased risks for poor health outcomes for these children and youths, and we know that there is a risk for mental health and psychosocial challenges for youth from these communities,” said Dr. Muñoz, a bilingual licensed psychologist and assistant professor of clinical pediatrics at the University of Southern California, Los Angeles.

In his presentation, Dr. Wagner said lumping racial and ethnic minority participants under a single BIPOC header probably wasn’t ideal because of the diversity and differences among racial and ethnic minorities. However, it was necessary in this particular study because of limited sample size.

Dr. Wagner and coauthors disclosed no conflicts of interest related to the research, which was supported by the Leona M. and Harry B. Helmsley Charitable Trust.

The risk of amputations in persons with type 1 diabetes in Sweden has decreased over time, suggesting an improvement in the course of disease for these individuals, according to a national registry analysis.

Balkonsky/Thinkstock

The incidence of any amputation trended downward from 2011 to 2019, Sara Hallström, MD, reported at the annual scientific sessions of the American Diabetes Association.

Levels of hemoglobin A1c have also trended downward over time in Sweden among those with type 1 diabetes, while renal function has remained stable among patients who did not undergo amputations, Dr. Hallström said in a virtual presentation.

“Observing stable renal function and decreasing levels of [hemoglobin] A1c, along with decreasing incidence of amputation, indicates a shift in the prognosis of persons with type 1 diabetes,” she said.
 

Drilling down on amputation risk in type 1 diabetes

Lower-extremity amputation is a major source of disability and distress in people with diabetes, and also poses a significant financial burden for the health care system, according to Dr. Hallström of Sahlgrenska University Hospital and the University of Gothenburg (Sweden).

“Limb loss due to amputation is not seldom a final outcome of diabetic foot ulcers,” she said in the presentation.

Most studies of amputation incidence and risk factors have grouped patients with different types of diabetes, though a few recent studies have singled out type 1 diabetes.

Among these is a 2019 study indicating a 40-fold higher risk of amputation among individuals with type 1 diabetes, compared with the general population, based on analysis of Swedish National Diabetes Register data from 1998 to 2013.
 

Trends over time

In the present study, Dr. Hallström and coinvestigators queried that same Swedish registry and identified 46,008 individuals with type 1 diabetes from 1998 to 2019. The mean age was 32.5 years and 55% were male. Overall, 1,519 of these individuals (3.3%) underwent amputation.

The incidence of any amputation fluctuated from 1998 to 2011, followed by a “decreasing trend over time” from 2011 to 2019, Dr. Hallström said.

The incidence of amputation per 1,000 patient-years was 2.84 in the earliest time period of 1998-2001, decreasing to 1.64 in 2017-2019.

Levels of A1c decreased over time, starting at 2012, both in participants with and without amputations, Dr. Hallström said. Renal function over that period remained stable in persons without amputation, and showed a decreasing trend in persons with amputation.

Compared with individuals with no amputations, those undergoing amputation were older (50 years vs. 32 years), had a longer duration of diabetes (34.9 years vs. 16.5 years), and had higher mean A1c, Dr. Hellström said. The amputee group also included a higher proportion of smokers, at 19.4% versus 14.0%, data show.

Risk factors for amputation included renal dysfunction, hyperglycemia, older age, smoking, hypertension, and cardiovascular comorbidities, according to the researcher.
 

U.S. amputations on the rise overall

While authors say results of this study point to a potentially improved prognosis for individuals with type 1 diabetes in Sweden, Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said amputation rates remains “concerning” based on U.S. data focused largely on type 2 diabetes.

“The amputation rate is unfortunately rising,” he said. “Sadly, this continues to be an issue.”

Significant health disparities persist, he added, with Black Americans having two- to threefold higher rates of amputations.

To help reduce amputation rates, clinicians should be asking patient about claudication and using simple screening techniques such as inspecting patient’s feet. “The big deal here is preventing ulcer formation, because once the ulcer forms, it often doesn’t heal, and it’s a downward spiral,” he said.

In addition, recent research suggests seeking a second opinion may help: “Many of those amputations could be avoided, in part because people aren’t aware of some of the treatments that can open up the arteries and reestablish blood flow,” he added.

Dr. Hallström reported no conflicts of interest. One coauthor on the study provided disclosures related to Abbott, AstraZeneca, Boehringer Ingelheim, Lilly Diabetes, and Novo Nordisk.

The risk of amputations in persons with type 1 diabetes in Sweden has decreased over time, suggesting an improvement in the course of disease for these individuals, according to a national registry analysis.

Balkonsky/Thinkstock

The incidence of any amputation trended downward from 2011 to 2019, Sara Hallström, MD, reported at the annual scientific sessions of the American Diabetes Association.

Levels of hemoglobin A1c have also trended downward over time in Sweden among those with type 1 diabetes, while renal function has remained stable among patients who did not undergo amputations, Dr. Hallström said in a virtual presentation.

“Observing stable renal function and decreasing levels of [hemoglobin] A1c, along with decreasing incidence of amputation, indicates a shift in the prognosis of persons with type 1 diabetes,” she said.
 

Drilling down on amputation risk in type 1 diabetes

Lower-extremity amputation is a major source of disability and distress in people with diabetes, and also poses a significant financial burden for the health care system, according to Dr. Hallström of Sahlgrenska University Hospital and the University of Gothenburg (Sweden).

“Limb loss due to amputation is not seldom a final outcome of diabetic foot ulcers,” she said in the presentation.

Most studies of amputation incidence and risk factors have grouped patients with different types of diabetes, though a few recent studies have singled out type 1 diabetes.

Among these is a 2019 study indicating a 40-fold higher risk of amputation among individuals with type 1 diabetes, compared with the general population, based on analysis of Swedish National Diabetes Register data from 1998 to 2013.
 

Trends over time

In the present study, Dr. Hallström and coinvestigators queried that same Swedish registry and identified 46,008 individuals with type 1 diabetes from 1998 to 2019. The mean age was 32.5 years and 55% were male. Overall, 1,519 of these individuals (3.3%) underwent amputation.

The incidence of any amputation fluctuated from 1998 to 2011, followed by a “decreasing trend over time” from 2011 to 2019, Dr. Hallström said.

The incidence of amputation per 1,000 patient-years was 2.84 in the earliest time period of 1998-2001, decreasing to 1.64 in 2017-2019.

Levels of A1c decreased over time, starting at 2012, both in participants with and without amputations, Dr. Hallström said. Renal function over that period remained stable in persons without amputation, and showed a decreasing trend in persons with amputation.

Compared with individuals with no amputations, those undergoing amputation were older (50 years vs. 32 years), had a longer duration of diabetes (34.9 years vs. 16.5 years), and had higher mean A1c, Dr. Hellström said. The amputee group also included a higher proportion of smokers, at 19.4% versus 14.0%, data show.

Risk factors for amputation included renal dysfunction, hyperglycemia, older age, smoking, hypertension, and cardiovascular comorbidities, according to the researcher.
 

U.S. amputations on the rise overall

While authors say results of this study point to a potentially improved prognosis for individuals with type 1 diabetes in Sweden, Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said amputation rates remains “concerning” based on U.S. data focused largely on type 2 diabetes.

“The amputation rate is unfortunately rising,” he said. “Sadly, this continues to be an issue.”

Significant health disparities persist, he added, with Black Americans having two- to threefold higher rates of amputations.

To help reduce amputation rates, clinicians should be asking patient about claudication and using simple screening techniques such as inspecting patient’s feet. “The big deal here is preventing ulcer formation, because once the ulcer forms, it often doesn’t heal, and it’s a downward spiral,” he said.

In addition, recent research suggests seeking a second opinion may help: “Many of those amputations could be avoided, in part because people aren’t aware of some of the treatments that can open up the arteries and reestablish blood flow,” he added.

Dr. Hallström reported no conflicts of interest. One coauthor on the study provided disclosures related to Abbott, AstraZeneca, Boehringer Ingelheim, Lilly Diabetes, and Novo Nordisk.

The risk of amputations in persons with type 1 diabetes in Sweden has decreased over time, suggesting an improvement in the course of disease for these individuals, according to a national registry analysis.

Balkonsky/Thinkstock

The incidence of any amputation trended downward from 2011 to 2019, Sara Hallström, MD, reported at the annual scientific sessions of the American Diabetes Association.

Levels of hemoglobin A1c have also trended downward over time in Sweden among those with type 1 diabetes, while renal function has remained stable among patients who did not undergo amputations, Dr. Hallström said in a virtual presentation.

“Observing stable renal function and decreasing levels of [hemoglobin] A1c, along with decreasing incidence of amputation, indicates a shift in the prognosis of persons with type 1 diabetes,” she said.
 

Drilling down on amputation risk in type 1 diabetes

Lower-extremity amputation is a major source of disability and distress in people with diabetes, and also poses a significant financial burden for the health care system, according to Dr. Hallström of Sahlgrenska University Hospital and the University of Gothenburg (Sweden).

“Limb loss due to amputation is not seldom a final outcome of diabetic foot ulcers,” she said in the presentation.

Most studies of amputation incidence and risk factors have grouped patients with different types of diabetes, though a few recent studies have singled out type 1 diabetes.

Among these is a 2019 study indicating a 40-fold higher risk of amputation among individuals with type 1 diabetes, compared with the general population, based on analysis of Swedish National Diabetes Register data from 1998 to 2013.
 

Trends over time

In the present study, Dr. Hallström and coinvestigators queried that same Swedish registry and identified 46,008 individuals with type 1 diabetes from 1998 to 2019. The mean age was 32.5 years and 55% were male. Overall, 1,519 of these individuals (3.3%) underwent amputation.

The incidence of any amputation fluctuated from 1998 to 2011, followed by a “decreasing trend over time” from 2011 to 2019, Dr. Hallström said.

The incidence of amputation per 1,000 patient-years was 2.84 in the earliest time period of 1998-2001, decreasing to 1.64 in 2017-2019.

Levels of A1c decreased over time, starting at 2012, both in participants with and without amputations, Dr. Hallström said. Renal function over that period remained stable in persons without amputation, and showed a decreasing trend in persons with amputation.

Compared with individuals with no amputations, those undergoing amputation were older (50 years vs. 32 years), had a longer duration of diabetes (34.9 years vs. 16.5 years), and had higher mean A1c, Dr. Hellström said. The amputee group also included a higher proportion of smokers, at 19.4% versus 14.0%, data show.

Risk factors for amputation included renal dysfunction, hyperglycemia, older age, smoking, hypertension, and cardiovascular comorbidities, according to the researcher.
 

U.S. amputations on the rise overall

While authors say results of this study point to a potentially improved prognosis for individuals with type 1 diabetes in Sweden, Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, said amputation rates remains “concerning” based on U.S. data focused largely on type 2 diabetes.

“The amputation rate is unfortunately rising,” he said. “Sadly, this continues to be an issue.”

Significant health disparities persist, he added, with Black Americans having two- to threefold higher rates of amputations.

To help reduce amputation rates, clinicians should be asking patient about claudication and using simple screening techniques such as inspecting patient’s feet. “The big deal here is preventing ulcer formation, because once the ulcer forms, it often doesn’t heal, and it’s a downward spiral,” he said.

In addition, recent research suggests seeking a second opinion may help: “Many of those amputations could be avoided, in part because people aren’t aware of some of the treatments that can open up the arteries and reestablish blood flow,” he added.

Dr. Hallström reported no conflicts of interest. One coauthor on the study provided disclosures related to Abbott, AstraZeneca, Boehringer Ingelheim, Lilly Diabetes, and Novo Nordisk.

Accumulating evidence shows that for many patients with type 2 diabetes, a bigger dose of the glucagonlike peptide–1 receptor agonist semaglutide is better if the goal is a larger decrease in hemoglobin A1c and weight.

Just weeks after the Food and Drug Administration approved an increased, 2.4-mg/week dose of semaglutide (Wegovy) for the indication of weight loss, results from a new randomized study with 961 patients that directly compared the standard 1.0-mg weekly dose for glycemic control with a 2.0-mg weekly dose showed that, over 40 weeks, the higher dose produced modest incremental improvements in both A1c reduction and weight loss while maintaining safety.

“Once weekly 2.0-mg subcutaneous semaglutide [Ozempic] was superior to 1.0 mg in reducing A1c, with greater weight loss and a similar safety profile,” Juan P. Frias, MD, said at the annual scientific sessions of the American Diabetes Association while presenting results of the SUSTAIN FORTE trial.

Average impact of the increased efficacy was measured. In the study’s “treatment policy estimand” analysis (considered equivalent to an intention-to-treat analysis), the primary endpoint of the cut in average A1c fell by a further 0.18% among patients on the higher dose, compared with the lower-dose arm, a significant difference in patients who entered the study with an average A1c of 8.9%. The average incremental boost for weight loss on the higher dose was about 0.8 kg, a difference that just missed significance (P = .0535).

In the study’s “trial product estimand” analysis (which censors data when patients stop the study drug or add on rescue medications), the effects were slightly more robust. The 2-mg dose produced an average 0.23% incremental decrease in A1c, compared with 1 mg, and an average incremental 0.93-kg weight reduction, both significant, reported Dr. Frias, an endocrinologist and medical director of the National Research Institute in Los Angeles.

Dr. Frias highlighted that these modest average differences had a clinical impact for some patients. In the treatment product estimand analysis, the percentage of patients achieving an A1c level of less than 7.0% increased from 58% of those who received 1 mg semaglutide to 68% of those treated with 2 mg, and achievement of an A1c of less than 6.5% occurred in 39% of patients on 1 mg and in 52% of those on 2 mg.

A similar pattern existed for weight loss in the treatment product estimand. Weight loss of at least 5% happened in 51% of patients on the 1-mg dose and in 59% of those on the higher dose.
 

Gradual up-titration aids tolerance

“The GLP-1 receptor agonists have so many benefits, but we were concerned in the past about pushing the dose. We’ve learned more about how to do that so that patients can better tolerate it,” commented Robert A. Gabbay, MD, PhD, chief science and medicine officer of the ADA in Arlington, Va. “The challenge with the medications from this class has been tolerability.”

Courtesy Joslin Diabetes Center

A key to minimizing adverse effects, especially gastrointestinal effects, from treatment with semaglutide and other GLP-1 receptor agonists has been more gradual up-titration to the target dose, Dr. Gabbay noted in an interview, and SUSTAIN FORTE took this approach. All patients started on a 0.25-mg injection of semaglutide once weekly for the first 4 weeks, followed by a 0.5-mg dose once weekly for 4 weeks, and then a 1.0 mg weekly dose. Patients in the arm randomized to receive 2.0 mg had one further dose escalation after receiving the 1.0-mg dose for 4 weeks.

The result was that gastrointestinal adverse effects occurred in 31% of patients maintained for 32 weeks on the 1-mg dose (with 40 total weeks of semaglutide treatment), and in 34% of patients who received the 2-mg dose for 28 weeks (and 40 total weeks of semaglutide treatment). Serious adverse events of all types occurred in 5% of patients in the 1-mg arm and in 4% of those on 2 mg. Total adverse events resulting in treatment discontinuation occurred in about 4.5% of patients in both arms, and discontinuations because of gastrointestinal effects occurred in about 3% of patients in both arms.

Severe hypoglycemia episodes occurred in 1 patient maintained on 1 mg weekly and in 2 patients in the 2-mg arm, while clinically significant episodes of hypoglycemia occurred in 18 patients on the 1-mg dose (4%) and in 12 of the patients on 2 mg (3%).

“It’s reassuring that the higher dose is tolerated,” commented Dr. Gabbay.
 

Several doses to choose from

SUSTAIN FORTE ran during 2019-2020 at about 125 centers in 10 countries, with roughly half the sites in the United States. It randomized adults with type 2 diabetes and an A1c of 8.0%-10.0% despite ongoing metformin treatment in all patients. Just over half the patients were also maintained on a sulfonylurea agent at entry. The enrolled patients had been diagnosed with diabetes for an average of about 10 years. They averaged 58 years of age, their body mass index averaged nearly 35 kg/m2, and about 58% were men.

The new evidence in support of a 2.0-mg weekly dose of semaglutide for patients with type 2 diabetes introduces a new wrinkle in a growing menu of dose options for this drug. On June 4, 2021, the FDA approved a weekly 2.4-mg dose of semaglutide for the indication of weight loss regardless of diabetes status in patients with a body mass index of 30 or higher (or in people at 27 or more with at least one weight-related comorbidity).

Dr. Gabbay suggested that, in practice, clinicians may focus more on treatment goals for individual patients rather than drug dose, especially with an agent that’s safer with slow dose titration.

In general, “clinicians establish a goal for each patient’s A1c; you use the drug dose that gets you there,” he observed.

SUSTAIN FORTE was sponsored by Novo Nordisk, the company that markets semaglutide. Dr. Frias has been a consultant to Novo Nordisk and numerous other companies, he has been a speaker on behalf of Lilly, Merck, and Sanofi, and he has received research funding from Novo Nordisk and numerous other companies. Dr. Gabbay had no relevant disclosures.

[email protected]

Accumulating evidence shows that for many patients with type 2 diabetes, a bigger dose of the glucagonlike peptide–1 receptor agonist semaglutide is better if the goal is a larger decrease in hemoglobin A1c and weight.

Just weeks after the Food and Drug Administration approved an increased, 2.4-mg/week dose of semaglutide (Wegovy) for the indication of weight loss, results from a new randomized study with 961 patients that directly compared the standard 1.0-mg weekly dose for glycemic control with a 2.0-mg weekly dose showed that, over 40 weeks, the higher dose produced modest incremental improvements in both A1c reduction and weight loss while maintaining safety.

“Once weekly 2.0-mg subcutaneous semaglutide [Ozempic] was superior to 1.0 mg in reducing A1c, with greater weight loss and a similar safety profile,” Juan P. Frias, MD, said at the annual scientific sessions of the American Diabetes Association while presenting results of the SUSTAIN FORTE trial.

Average impact of the increased efficacy was measured. In the study’s “treatment policy estimand” analysis (considered equivalent to an intention-to-treat analysis), the primary endpoint of the cut in average A1c fell by a further 0.18% among patients on the higher dose, compared with the lower-dose arm, a significant difference in patients who entered the study with an average A1c of 8.9%. The average incremental boost for weight loss on the higher dose was about 0.8 kg, a difference that just missed significance (P = .0535).

In the study’s “trial product estimand” analysis (which censors data when patients stop the study drug or add on rescue medications), the effects were slightly more robust. The 2-mg dose produced an average 0.23% incremental decrease in A1c, compared with 1 mg, and an average incremental 0.93-kg weight reduction, both significant, reported Dr. Frias, an endocrinologist and medical director of the National Research Institute in Los Angeles.

Dr. Frias highlighted that these modest average differences had a clinical impact for some patients. In the treatment product estimand analysis, the percentage of patients achieving an A1c level of less than 7.0% increased from 58% of those who received 1 mg semaglutide to 68% of those treated with 2 mg, and achievement of an A1c of less than 6.5% occurred in 39% of patients on 1 mg and in 52% of those on 2 mg.

A similar pattern existed for weight loss in the treatment product estimand. Weight loss of at least 5% happened in 51% of patients on the 1-mg dose and in 59% of those on the higher dose.
 

Gradual up-titration aids tolerance

“The GLP-1 receptor agonists have so many benefits, but we were concerned in the past about pushing the dose. We’ve learned more about how to do that so that patients can better tolerate it,” commented Robert A. Gabbay, MD, PhD, chief science and medicine officer of the ADA in Arlington, Va. “The challenge with the medications from this class has been tolerability.”

Courtesy Joslin Diabetes Center

A key to minimizing adverse effects, especially gastrointestinal effects, from treatment with semaglutide and other GLP-1 receptor agonists has been more gradual up-titration to the target dose, Dr. Gabbay noted in an interview, and SUSTAIN FORTE took this approach. All patients started on a 0.25-mg injection of semaglutide once weekly for the first 4 weeks, followed by a 0.5-mg dose once weekly for 4 weeks, and then a 1.0 mg weekly dose. Patients in the arm randomized to receive 2.0 mg had one further dose escalation after receiving the 1.0-mg dose for 4 weeks.

The result was that gastrointestinal adverse effects occurred in 31% of patients maintained for 32 weeks on the 1-mg dose (with 40 total weeks of semaglutide treatment), and in 34% of patients who received the 2-mg dose for 28 weeks (and 40 total weeks of semaglutide treatment). Serious adverse events of all types occurred in 5% of patients in the 1-mg arm and in 4% of those on 2 mg. Total adverse events resulting in treatment discontinuation occurred in about 4.5% of patients in both arms, and discontinuations because of gastrointestinal effects occurred in about 3% of patients in both arms.

Severe hypoglycemia episodes occurred in 1 patient maintained on 1 mg weekly and in 2 patients in the 2-mg arm, while clinically significant episodes of hypoglycemia occurred in 18 patients on the 1-mg dose (4%) and in 12 of the patients on 2 mg (3%).

“It’s reassuring that the higher dose is tolerated,” commented Dr. Gabbay.
 

Several doses to choose from

SUSTAIN FORTE ran during 2019-2020 at about 125 centers in 10 countries, with roughly half the sites in the United States. It randomized adults with type 2 diabetes and an A1c of 8.0%-10.0% despite ongoing metformin treatment in all patients. Just over half the patients were also maintained on a sulfonylurea agent at entry. The enrolled patients had been diagnosed with diabetes for an average of about 10 years. They averaged 58 years of age, their body mass index averaged nearly 35 kg/m2, and about 58% were men.

The new evidence in support of a 2.0-mg weekly dose of semaglutide for patients with type 2 diabetes introduces a new wrinkle in a growing menu of dose options for this drug. On June 4, 2021, the FDA approved a weekly 2.4-mg dose of semaglutide for the indication of weight loss regardless of diabetes status in patients with a body mass index of 30 or higher (or in people at 27 or more with at least one weight-related comorbidity).

Dr. Gabbay suggested that, in practice, clinicians may focus more on treatment goals for individual patients rather than drug dose, especially with an agent that’s safer with slow dose titration.

In general, “clinicians establish a goal for each patient’s A1c; you use the drug dose that gets you there,” he observed.

SUSTAIN FORTE was sponsored by Novo Nordisk, the company that markets semaglutide. Dr. Frias has been a consultant to Novo Nordisk and numerous other companies, he has been a speaker on behalf of Lilly, Merck, and Sanofi, and he has received research funding from Novo Nordisk and numerous other companies. Dr. Gabbay had no relevant disclosures.

[email protected]

Accumulating evidence shows that for many patients with type 2 diabetes, a bigger dose of the glucagonlike peptide–1 receptor agonist semaglutide is better if the goal is a larger decrease in hemoglobin A1c and weight.

Just weeks after the Food and Drug Administration approved an increased, 2.4-mg/week dose of semaglutide (Wegovy) for the indication of weight loss, results from a new randomized study with 961 patients that directly compared the standard 1.0-mg weekly dose for glycemic control with a 2.0-mg weekly dose showed that, over 40 weeks, the higher dose produced modest incremental improvements in both A1c reduction and weight loss while maintaining safety.

“Once weekly 2.0-mg subcutaneous semaglutide [Ozempic] was superior to 1.0 mg in reducing A1c, with greater weight loss and a similar safety profile,” Juan P. Frias, MD, said at the annual scientific sessions of the American Diabetes Association while presenting results of the SUSTAIN FORTE trial.

Average impact of the increased efficacy was measured. In the study’s “treatment policy estimand” analysis (considered equivalent to an intention-to-treat analysis), the primary endpoint of the cut in average A1c fell by a further 0.18% among patients on the higher dose, compared with the lower-dose arm, a significant difference in patients who entered the study with an average A1c of 8.9%. The average incremental boost for weight loss on the higher dose was about 0.8 kg, a difference that just missed significance (P = .0535).

In the study’s “trial product estimand” analysis (which censors data when patients stop the study drug or add on rescue medications), the effects were slightly more robust. The 2-mg dose produced an average 0.23% incremental decrease in A1c, compared with 1 mg, and an average incremental 0.93-kg weight reduction, both significant, reported Dr. Frias, an endocrinologist and medical director of the National Research Institute in Los Angeles.

Dr. Frias highlighted that these modest average differences had a clinical impact for some patients. In the treatment product estimand analysis, the percentage of patients achieving an A1c level of less than 7.0% increased from 58% of those who received 1 mg semaglutide to 68% of those treated with 2 mg, and achievement of an A1c of less than 6.5% occurred in 39% of patients on 1 mg and in 52% of those on 2 mg.

A similar pattern existed for weight loss in the treatment product estimand. Weight loss of at least 5% happened in 51% of patients on the 1-mg dose and in 59% of those on the higher dose.
 

Gradual up-titration aids tolerance

“The GLP-1 receptor agonists have so many benefits, but we were concerned in the past about pushing the dose. We’ve learned more about how to do that so that patients can better tolerate it,” commented Robert A. Gabbay, MD, PhD, chief science and medicine officer of the ADA in Arlington, Va. “The challenge with the medications from this class has been tolerability.”

Courtesy Joslin Diabetes Center

A key to minimizing adverse effects, especially gastrointestinal effects, from treatment with semaglutide and other GLP-1 receptor agonists has been more gradual up-titration to the target dose, Dr. Gabbay noted in an interview, and SUSTAIN FORTE took this approach. All patients started on a 0.25-mg injection of semaglutide once weekly for the first 4 weeks, followed by a 0.5-mg dose once weekly for 4 weeks, and then a 1.0 mg weekly dose. Patients in the arm randomized to receive 2.0 mg had one further dose escalation after receiving the 1.0-mg dose for 4 weeks.

The result was that gastrointestinal adverse effects occurred in 31% of patients maintained for 32 weeks on the 1-mg dose (with 40 total weeks of semaglutide treatment), and in 34% of patients who received the 2-mg dose for 28 weeks (and 40 total weeks of semaglutide treatment). Serious adverse events of all types occurred in 5% of patients in the 1-mg arm and in 4% of those on 2 mg. Total adverse events resulting in treatment discontinuation occurred in about 4.5% of patients in both arms, and discontinuations because of gastrointestinal effects occurred in about 3% of patients in both arms.

Severe hypoglycemia episodes occurred in 1 patient maintained on 1 mg weekly and in 2 patients in the 2-mg arm, while clinically significant episodes of hypoglycemia occurred in 18 patients on the 1-mg dose (4%) and in 12 of the patients on 2 mg (3%).

“It’s reassuring that the higher dose is tolerated,” commented Dr. Gabbay.
 

Several doses to choose from

SUSTAIN FORTE ran during 2019-2020 at about 125 centers in 10 countries, with roughly half the sites in the United States. It randomized adults with type 2 diabetes and an A1c of 8.0%-10.0% despite ongoing metformin treatment in all patients. Just over half the patients were also maintained on a sulfonylurea agent at entry. The enrolled patients had been diagnosed with diabetes for an average of about 10 years. They averaged 58 years of age, their body mass index averaged nearly 35 kg/m2, and about 58% were men.

The new evidence in support of a 2.0-mg weekly dose of semaglutide for patients with type 2 diabetes introduces a new wrinkle in a growing menu of dose options for this drug. On June 4, 2021, the FDA approved a weekly 2.4-mg dose of semaglutide for the indication of weight loss regardless of diabetes status in patients with a body mass index of 30 or higher (or in people at 27 or more with at least one weight-related comorbidity).

Dr. Gabbay suggested that, in practice, clinicians may focus more on treatment goals for individual patients rather than drug dose, especially with an agent that’s safer with slow dose titration.

In general, “clinicians establish a goal for each patient’s A1c; you use the drug dose that gets you there,” he observed.

SUSTAIN FORTE was sponsored by Novo Nordisk, the company that markets semaglutide. Dr. Frias has been a consultant to Novo Nordisk and numerous other companies, he has been a speaker on behalf of Lilly, Merck, and Sanofi, and he has received research funding from Novo Nordisk and numerous other companies. Dr. Gabbay had no relevant disclosures.

[email protected]

Editor’s note: This article has been provided by The Doctors Company, the exclusively endorsed medical malpractice carrier for the Society of Hospital Medicine.

Artificial intelligence (AI) has proven of value in the COVID-19 pandemic and shows promise for mitigating future health care crises. During the pandemic’s first wave in New York, for example, Mount Sinai Health System used an algorithm to help identify patients ready for discharge. Such systems can help overburdened hospitals manage personnel and the flow of supplies in a medical crisis so they can continue to provide superior patient care.¹

Pandemic applications have demonstrated AI’s potential not only to lift administrative burdens, but also to give physicians back what Eric Topol, MD, founder and director of Scripps Research Translational Institute and author of Deep Medicine, calls “the gift of time.”² More time with patients contributes to clear communication and positive relationships, which lower the odds of medical errors, enhance patient safety, and potentially reduce physicians’ risks of certain types of litigation.³

However, physicians and health systems will need to approach AI with caution. Many unknowns remain – including potential liability risks and the potential for worsening preexisting bias. The law will need to evolve to account for AI-related liability scenarios, some of which are yet to be imagined.

Like any emerging technology, AI brings risk, but its promise of benefit should outweigh the probability of negative consequences – provided we remain aware of and mitigate the potential for AI-induced adverse events.
 

AI’s pandemic success limited due to fragmented data

Innovation is the key to success in any crisis, and many health care providers have shown their ability to innovate with AI during the pandemic. For example, researchers at the University of California, San Diego, health system who were designing an AI program to help doctors spot pneumonia on a chest x-ray retooled their application to assist physicians fighting coronavirus.⁴

Meanwhile, AI has been used to distinguish COVID-19–specific symptoms: It was a computer sifting medical records that took anosmia, loss of the sense of smell, from an anecdotal connection to an officially recognized early symptom of the virus.⁵ This information now helps physicians distinguish COVID-19 from influenza.

However, holding back more innovation is the fragmentation of health care data in the United States. Most AI applications for medicine rely on machine learning; that is, they train on historical patient data to recognize patterns. Therefore, “Everything that we’re doing gets better with a lot more annotated datasets,” Dr. Topol says. Unfortunately, because of our disparate systems, we don’t have centralized data.⁶ And even if our data were centralized, researchers lack enough reliable COVID-19 data to perfect algorithms in the short term.

Or, put in bleaker terms by the Washington Post: “One of the biggest challenges has been that much data remains siloed inside incompatible computer systems, hoarded by business interests and tangled in geopolitics.”⁷

The good news is that machine learning and data science platform Kaggle is hosting the COVID-19 Open Research Dataset, or CORD-19, which contains well over 100,000 scholarly articles on COVID-19, SARS, and other relevant infections.⁸ In lieu of a true central repository of anonymized health data, such large datasets can help train new AI applications in search of new diagnostic tools and therapies.
 

AI introduces new questions around liability

While AI may eventually be assigned legal personhood, it is not, in fact, a person: It is a tool wielded by individual clinicians, by teams, by health systems, even multiple systems collaborating. Our current liability laws are not ready for the era of digital medicine.

AI algorithms are not perfect. Because we know that diagnostic error is already a major allegation in malpractice claims, we must ask: What happens when a patient alleges that diagnostic error occurred because a physician or physicians leaned too heavily on AI?

In the United States, testing delays have threatened the safety of patients, physicians, and the public by delaying diagnosis of COVID-19. But again, health care providers have applied real innovation – generating novel and useful ideas and applying those ideas – to this problem. For example, researchers at Mount Sinai became the first in the country to combine AI with imaging and clinical data to produce an algorithm that can detect COVID-19 based on computed tomography scans of the chest, in combination with patient information and exposure history.⁹
 

AI in health care can help mitigate bias – or worsen it

Machine learning is only as good as the information provided to train the machine. Models trained on partial datasets can skew toward demographics that turned up more often in the data – for example, White race or men over 60. There is concern that “analyses based on faulty or biased algorithms could exacerbate existing racial gaps and other disparities in health care.”¹⁰ Already during the pandemic’s first waves, multiple AI systems used to classify x-rays have been found to show racial, gender, and socioeconomic biases.¹¹

Such bias could create high potential for poor recommendations, including false positives and false negatives. It’s critical that system builders are able to explain and qualify their training data and that those who best understand AI-related system risks are the ones who influence health care systems or alter applications to mitigate AI-related harms.¹²

AI can help spot the next outbreak

More than a week before the World Health Organization released its first warning about a novel coronavirus, the AI platform BlueDot, created in Toronto, spotted an unusual cluster of pneumonia cases in Wuhan, China. Meanwhile, at Boston Children’s Hospital, the AI application Healthmap was scanning social media and news sites for signs of disease cluster, and it, too, flagged the first signs of what would become the COVID-19 outbreak – days before the WHO’s first formal alert.¹³

These innovative applications of AI in health care demonstrate real promise in detecting future outbreaks of new viruses early. This will allow health care providers and public health officials to get information out sooner, reducing the load on health systems, and ultimately, saving lives.
 

Dr. Anderson is chairman and chief executive officer, The Doctors Company and TDC Group.

References

1. Gold A. “Coronavirus tests the value of artificial intelligence in medicine” Fierce Biotech. 2020 May 22.

2. Topol E. “Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again” (New York: Hachette Book Group; 2019:285).

3. The Doctors Company. “The Algorithm Will See You Now: How AI’s Healthcare Potential Outweighs Its Risk” 2020 Jan.

4. Gold A. Coronavirus tests the value of artificial intelligence in medicine. Fierce Biotech. 2020 May 22.

5. Cha AE. Artificial intelligence and COVID-19: Can the machines save us? Washington Post. 2020 Nov 1.

6. Reuter E. Hundreds of AI solutions proposed for pandemic, but few are proven. MedCity News. 2020 May 28.

7. Cha AE. Artificial intelligence and COVID-19: Can the machines save us? Washington Post. 2020 Nov 1.

8. Lee K. COVID-19 will accelerate the AI health care revolution. Wired. 2020 May 22.

9. Mei X et al. Artificial intelligence–enabled rapid diagnosis of patients with COVID-19. Nat Med. 2020 May 19;26:1224-8. doi: 10.1038/s41591-020-0931-3.

10. Cha AE. Artificial intelligence and COVID-19: Can the machines save us? Washington Post. 2020 Nov 1.

11. Wiggers K. Researchers find evidence of racial, gender, and socioeconomic bias in chest X-ray classifiers. The Machine: Making Sense of AI. 2020 Oct 21.

12. The Doctors Company. “The Algorithm Will See You Now: How AI’s Healthcare Potential Outweighs Its Risk” 2020 Jan.

13. Sewalk K. Innovative disease surveillance platforms detected early warning signs for novel coronavirus outbreak (nCoV-2019). The Disease Daily. 2020 Jan 31.
 

Editor’s note: This article has been provided by The Doctors Company, the exclusively endorsed medical malpractice carrier for the Society of Hospital Medicine.

Artificial intelligence (AI) has proven of value in the COVID-19 pandemic and shows promise for mitigating future health care crises. During the pandemic’s first wave in New York, for example, Mount Sinai Health System used an algorithm to help identify patients ready for discharge. Such systems can help overburdened hospitals manage personnel and the flow of supplies in a medical crisis so they can continue to provide superior patient care.¹

Pandemic applications have demonstrated AI’s potential not only to lift administrative burdens, but also to give physicians back what Eric Topol, MD, founder and director of Scripps Research Translational Institute and author of Deep Medicine, calls “the gift of time.”² More time with patients contributes to clear communication and positive relationships, which lower the odds of medical errors, enhance patient safety, and potentially reduce physicians’ risks of certain types of litigation.³

However, physicians and health systems will need to approach AI with caution. Many unknowns remain – including potential liability risks and the potential for worsening preexisting bias. The law will need to evolve to account for AI-related liability scenarios, some of which are yet to be imagined.

Like any emerging technology, AI brings risk, but its promise of benefit should outweigh the probability of negative consequences – provided we remain aware of and mitigate the potential for AI-induced adverse events.
 

AI’s pandemic success limited due to fragmented data

Innovation is the key to success in any crisis, and many health care providers have shown their ability to innovate with AI during the pandemic. For example, researchers at the University of California, San Diego, health system who were designing an AI program to help doctors spot pneumonia on a chest x-ray retooled their application to assist physicians fighting coronavirus.⁴

Meanwhile, AI has been used to distinguish COVID-19–specific symptoms: It was a computer sifting medical records that took anosmia, loss of the sense of smell, from an anecdotal connection to an officially recognized early symptom of the virus.⁵ This information now helps physicians distinguish COVID-19 from influenza.

However, holding back more innovation is the fragmentation of health care data in the United States. Most AI applications for medicine rely on machine learning; that is, they train on historical patient data to recognize patterns. Therefore, “Everything that we’re doing gets better with a lot more annotated datasets,” Dr. Topol says. Unfortunately, because of our disparate systems, we don’t have centralized data.⁶ And even if our data were centralized, researchers lack enough reliable COVID-19 data to perfect algorithms in the short term.

Or, put in bleaker terms by the Washington Post: “One of the biggest challenges has been that much data remains siloed inside incompatible computer systems, hoarded by business interests and tangled in geopolitics.”⁷

The good news is that machine learning and data science platform Kaggle is hosting the COVID-19 Open Research Dataset, or CORD-19, which contains well over 100,000 scholarly articles on COVID-19, SARS, and other relevant infections.⁸ In lieu of a true central repository of anonymized health data, such large datasets can help train new AI applications in search of new diagnostic tools and therapies.
 

AI introduces new questions around liability

While AI may eventually be assigned legal personhood, it is not, in fact, a person: It is a tool wielded by individual clinicians, by teams, by health systems, even multiple systems collaborating. Our current liability laws are not ready for the era of digital medicine.

AI algorithms are not perfect. Because we know that diagnostic error is already a major allegation in malpractice claims, we must ask: What happens when a patient alleges that diagnostic error occurred because a physician or physicians leaned too heavily on AI?

In the United States, testing delays have threatened the safety of patients, physicians, and the public by delaying diagnosis of COVID-19. But again, health care providers have applied real innovation – generating novel and useful ideas and applying those ideas – to this problem. For example, researchers at Mount Sinai became the first in the country to combine AI with imaging and clinical data to produce an algorithm that can detect COVID-19 based on computed tomography scans of the chest, in combination with patient information and exposure history.⁹
 

AI in health care can help mitigate bias – or worsen it

Machine learning is only as good as the information provided to train the machine. Models trained on partial datasets can skew toward demographics that turned up more often in the data – for example, White race or men over 60. There is concern that “analyses based on faulty or biased algorithms could exacerbate existing racial gaps and other disparities in health care.”¹⁰ Already during the pandemic’s first waves, multiple AI systems used to classify x-rays have been found to show racial, gender, and socioeconomic biases.¹¹

Such bias could create high potential for poor recommendations, including false positives and false negatives. It’s critical that system builders are able to explain and qualify their training data and that those who best understand AI-related system risks are the ones who influence health care systems or alter applications to mitigate AI-related harms.¹²

AI can help spot the next outbreak

More than a week before the World Health Organization released its first warning about a novel coronavirus, the AI platform BlueDot, created in Toronto, spotted an unusual cluster of pneumonia cases in Wuhan, China. Meanwhile, at Boston Children’s Hospital, the AI application Healthmap was scanning social media and news sites for signs of disease cluster, and it, too, flagged the first signs of what would become the COVID-19 outbreak – days before the WHO’s first formal alert.¹³

These innovative applications of AI in health care demonstrate real promise in detecting future outbreaks of new viruses early. This will allow health care providers and public health officials to get information out sooner, reducing the load on health systems, and ultimately, saving lives.
 

Dr. Anderson is chairman and chief executive officer, The Doctors Company and TDC Group.

References

1. Gold A. “Coronavirus tests the value of artificial intelligence in medicine” Fierce Biotech. 2020 May 22.

2. Topol E. “Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again” (New York: Hachette Book Group; 2019:285).

3. The Doctors Company. “The Algorithm Will See You Now: How AI’s Healthcare Potential Outweighs Its Risk” 2020 Jan.

4. Gold A. Coronavirus tests the value of artificial intelligence in medicine. Fierce Biotech. 2020 May 22.

5. Cha AE. Artificial intelligence and COVID-19: Can the machines save us? Washington Post. 2020 Nov 1.

6. Reuter E. Hundreds of AI solutions proposed for pandemic, but few are proven. MedCity News. 2020 May 28.

7. Cha AE. Artificial intelligence and COVID-19: Can the machines save us? Washington Post. 2020 Nov 1.

8. Lee K. COVID-19 will accelerate the AI health care revolution. Wired. 2020 May 22.

9. Mei X et al. Artificial intelligence–enabled rapid diagnosis of patients with COVID-19. Nat Med. 2020 May 19;26:1224-8. doi: 10.1038/s41591-020-0931-3.

10. Cha AE. Artificial intelligence and COVID-19: Can the machines save us? Washington Post. 2020 Nov 1.

11. Wiggers K. Researchers find evidence of racial, gender, and socioeconomic bias in chest X-ray classifiers. The Machine: Making Sense of AI. 2020 Oct 21.

12. The Doctors Company. “The Algorithm Will See You Now: How AI’s Healthcare Potential Outweighs Its Risk” 2020 Jan.

13. Sewalk K. Innovative disease surveillance platforms detected early warning signs for novel coronavirus outbreak (nCoV-2019). The Disease Daily. 2020 Jan 31.
 

Editor’s note: This article has been provided by The Doctors Company, the exclusively endorsed medical malpractice carrier for the Society of Hospital Medicine.

Artificial intelligence (AI) has proven of value in the COVID-19 pandemic and shows promise for mitigating future health care crises. During the pandemic’s first wave in New York, for example, Mount Sinai Health System used an algorithm to help identify patients ready for discharge. Such systems can help overburdened hospitals manage personnel and the flow of supplies in a medical crisis so they can continue to provide superior patient care.¹

Pandemic applications have demonstrated AI’s potential not only to lift administrative burdens, but also to give physicians back what Eric Topol, MD, founder and director of Scripps Research Translational Institute and author of Deep Medicine, calls “the gift of time.”² More time with patients contributes to clear communication and positive relationships, which lower the odds of medical errors, enhance patient safety, and potentially reduce physicians’ risks of certain types of litigation.³

However, physicians and health systems will need to approach AI with caution. Many unknowns remain – including potential liability risks and the potential for worsening preexisting bias. The law will need to evolve to account for AI-related liability scenarios, some of which are yet to be imagined.

Like any emerging technology, AI brings risk, but its promise of benefit should outweigh the probability of negative consequences – provided we remain aware of and mitigate the potential for AI-induced adverse events.
 

AI’s pandemic success limited due to fragmented data

Innovation is the key to success in any crisis, and many health care providers have shown their ability to innovate with AI during the pandemic. For example, researchers at the University of California, San Diego, health system who were designing an AI program to help doctors spot pneumonia on a chest x-ray retooled their application to assist physicians fighting coronavirus.⁴

Meanwhile, AI has been used to distinguish COVID-19–specific symptoms: It was a computer sifting medical records that took anosmia, loss of the sense of smell, from an anecdotal connection to an officially recognized early symptom of the virus.⁵ This information now helps physicians distinguish COVID-19 from influenza.

However, holding back more innovation is the fragmentation of health care data in the United States. Most AI applications for medicine rely on machine learning; that is, they train on historical patient data to recognize patterns. Therefore, “Everything that we’re doing gets better with a lot more annotated datasets,” Dr. Topol says. Unfortunately, because of our disparate systems, we don’t have centralized data.⁶ And even if our data were centralized, researchers lack enough reliable COVID-19 data to perfect algorithms in the short term.

Or, put in bleaker terms by the Washington Post: “One of the biggest challenges has been that much data remains siloed inside incompatible computer systems, hoarded by business interests and tangled in geopolitics.”⁷

The good news is that machine learning and data science platform Kaggle is hosting the COVID-19 Open Research Dataset, or CORD-19, which contains well over 100,000 scholarly articles on COVID-19, SARS, and other relevant infections.⁸ In lieu of a true central repository of anonymized health data, such large datasets can help train new AI applications in search of new diagnostic tools and therapies.
 

AI introduces new questions around liability

While AI may eventually be assigned legal personhood, it is not, in fact, a person: It is a tool wielded by individual clinicians, by teams, by health systems, even multiple systems collaborating. Our current liability laws are not ready for the era of digital medicine.

AI algorithms are not perfect. Because we know that diagnostic error is already a major allegation in malpractice claims, we must ask: What happens when a patient alleges that diagnostic error occurred because a physician or physicians leaned too heavily on AI?

In the United States, testing delays have threatened the safety of patients, physicians, and the public by delaying diagnosis of COVID-19. But again, health care providers have applied real innovation – generating novel and useful ideas and applying those ideas – to this problem. For example, researchers at Mount Sinai became the first in the country to combine AI with imaging and clinical data to produce an algorithm that can detect COVID-19 based on computed tomography scans of the chest, in combination with patient information and exposure history.⁹
 

AI in health care can help mitigate bias – or worsen it

Machine learning is only as good as the information provided to train the machine. Models trained on partial datasets can skew toward demographics that turned up more often in the data – for example, White race or men over 60. There is concern that “analyses based on faulty or biased algorithms could exacerbate existing racial gaps and other disparities in health care.”¹⁰ Already during the pandemic’s first waves, multiple AI systems used to classify x-rays have been found to show racial, gender, and socioeconomic biases.¹¹

Such bias could create high potential for poor recommendations, including false positives and false negatives. It’s critical that system builders are able to explain and qualify their training data and that those who best understand AI-related system risks are the ones who influence health care systems or alter applications to mitigate AI-related harms.¹²

AI can help spot the next outbreak

More than a week before the World Health Organization released its first warning about a novel coronavirus, the AI platform BlueDot, created in Toronto, spotted an unusual cluster of pneumonia cases in Wuhan, China. Meanwhile, at Boston Children’s Hospital, the AI application Healthmap was scanning social media and news sites for signs of disease cluster, and it, too, flagged the first signs of what would become the COVID-19 outbreak – days before the WHO’s first formal alert.¹³

These innovative applications of AI in health care demonstrate real promise in detecting future outbreaks of new viruses early. This will allow health care providers and public health officials to get information out sooner, reducing the load on health systems, and ultimately, saving lives.
 

Dr. Anderson is chairman and chief executive officer, The Doctors Company and TDC Group.

References

1. Gold A. “Coronavirus tests the value of artificial intelligence in medicine” Fierce Biotech. 2020 May 22.

2. Topol E. “Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again” (New York: Hachette Book Group; 2019:285).

3. The Doctors Company. “The Algorithm Will See You Now: How AI’s Healthcare Potential Outweighs Its Risk” 2020 Jan.

4. Gold A. Coronavirus tests the value of artificial intelligence in medicine. Fierce Biotech. 2020 May 22.

5. Cha AE. Artificial intelligence and COVID-19: Can the machines save us? Washington Post. 2020 Nov 1.

6. Reuter E. Hundreds of AI solutions proposed for pandemic, but few are proven. MedCity News. 2020 May 28.

7. Cha AE. Artificial intelligence and COVID-19: Can the machines save us? Washington Post. 2020 Nov 1.

8. Lee K. COVID-19 will accelerate the AI health care revolution. Wired. 2020 May 22.

9. Mei X et al. Artificial intelligence–enabled rapid diagnosis of patients with COVID-19. Nat Med. 2020 May 19;26:1224-8. doi: 10.1038/s41591-020-0931-3.

10. Cha AE. Artificial intelligence and COVID-19: Can the machines save us? Washington Post. 2020 Nov 1.

11. Wiggers K. Researchers find evidence of racial, gender, and socioeconomic bias in chest X-ray classifiers. The Machine: Making Sense of AI. 2020 Oct 21.

12. The Doctors Company. “The Algorithm Will See You Now: How AI’s Healthcare Potential Outweighs Its Risk” 2020 Jan.

13. Sewalk K. Innovative disease surveillance platforms detected early warning signs for novel coronavirus outbreak (nCoV-2019). The Disease Daily. 2020 Jan 31.
 

The incidence of type 2 diabetes in children appears to have doubled during the COVID-19 pandemic, data from two new U.S. studies suggest, with the lead investigator of one saying she was “surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”

Anetta_R/Thinkstock

Findings from the two separate retrospective chart reviews – one conducted in Washington, D.C., and the other in Baton Rouge, La. – were presented June 25 at the annual scientific sessions of the American Diabetes Association.

Although the two studies differed somewhat in the clinical parameters examined, both revealed a similar doubling of the rates of hospitalizations for type 2 diabetes among youth during 2020, compared with the same time period in 2019, as well as greater severity of metabolic disturbance.

And, as has been previously described with type 2 diabetes in youth, African American ethnicity predominated in both cohorts.

“Although we could not assess the cause of the increases in type 2 diabetes from our data, these disparities suggest that indirect effects of social distancing measures, including school closure and unemployment, are placing undue burden on underserved communities. Decreases in well-child care and fears of seeking medical care during the pandemic may have also contributed,” lead investigator of one of the studies, pediatric endocrinologist Brynn E. Marks, MD, Children’s National Hospital, Washington, said in an interview.
 

More hospitalizations, racial disparities aggravated by COVID-19

Lead author of the other study, Daniel S. Hsia, MD, Pennington Biomedical Research Center, Baton Rouge, said in an interview: “Since the pandemic, our data suggest that more children may be diagnosed with type 2 diabetes and may require hospitalization when they are diagnosed. Looking at both datasets, there appears to be a racial disparity in type 2 diabetes diagnoses that has only been exacerbated by the COVID-19 pandemic.”

Of concern, Dr. Hsia said, “The incidence rate of type 2 diabetes in children was already on the rise before the pandemic. While there may be a brief leveling off now that children are getting regular health care and going back to school in person, I believe these rates will continue to rise especially in light of the childhood obesity rates not improving.”

Their dataset captured all youth who were newly diagnosed with type 2 diabetes during the first full year of the COVID-19 pandemic, from March 11, 2020, to March 10, 2021, and compared those data with the time period from March 11, 2019, to March 10, 2020.

During the pandemic, the number of cases of type 2 diabetes increased by 182%, from 50 in 2019 to 141 in 2020. The average age at diagnosis was about 14 years in both time periods.

In the prepandemic period, 18 (36%) diagnosed with type 2 diabetes required inpatient admission, compared with 85 (60.3%) during the pandemic. At Children’s National, youth with suspected new-onset type 2 diabetes aren’t typically hospitalized unless they have severe hyperglycemia, ketosis, or are unable to schedule urgent outpatient follow-up, Dr. Marks noted.

The proportions of youth with new-onset type 2 diabetes who presented in diabetic ketoacidosis (DKA) rose from 2 (4%) prepandemic to 33 (23.4%) during the pandemic. Presentation with hyperosmolar DKA rose from 0 to 13 (9.2%).

However, during the pandemic only five youth were actively infected with SARS-CoV-2 at the time of type 2 diabetes diagnosis among the 90 tested.

Dr. Marks said: “We believe the increase in inpatient admissions was due to more severe presentation during the pandemic. ...We were surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”
 

Shift in diagnoses to type 2 diabetes

The pandemic also appears to have shifted the proportion of youth diagnosed with type 2 diabetes, compared with type 1 diabetes. Whereas 24% of youth with new-onset diabetes prepandemic had type 2 diabetes and the rest had type 1 diabetes, during pandemic the proportion with type 2 diabetes rose to 44%.

“Rates of type 2 diabetes rose steadily at a rate of 1.45 cases per month throughout the course of the pandemic, suggesting a cumulative effect of the indirect effects of social distancing measures,” Dr. Marks said.

Furthermore, she added, whereas 60% of youth diagnosed with type 2 diabetes before the pandemic were female, the rate fell to 40% during the pandemic. This trend might be because of activity levels in that, while male adolescents are typically more active, rates of exercise fell in both sexes during the pandemic but declined more sharply in males such that activity levels between the sexes became equal.  

Although type 2 diabetes in youth has always been more common in ethnic minorities, the pandemic appears to have exacerbated these disparities.

While 58% of youth diagnosed with type 2 diabetes prepandemic identified as non-Hispanic Black, that proportion rose to 76.7% during the pandemic. Among Black youth with new-onset type 2 diabetes, 31 of 33 presented in DKA, and 12 of the 13 who presented in hyperosmolar DKA during the pandemic were Black.

“Strategies to promote health equity and address the undue burden of the COVID-19 pandemic on underserved communities must be developed to avoid worsening disparities and long-term health outcomes,” Dr. Marks said.
 

‘A microcosm’: Similar findings in a smaller population

Dr. Hsia and colleagues looked at a smaller number of patients in a shorter time period. In March–December 2019, the hospitalization rate for new-onset type 2 diabetes was 0.27% (8 out of 2,964 hospitalizations), compared with 0.62% (17 out of 2,729 hospitalizations) during the same period in 2020 (P < .048) – also more than a doubling. Age at admission, sex, and body mass index didn’t differ between the two groups.

Criteria for DKA were met by three children in 2019 versus eight in 2020, and hyperosmolar hyperglycemic syndrome in zero versus two, respectively. Mean hemoglobin A1c on admission was 12.4% in 2019 versus 13.1% in 2020 (P = .59), and mean serum glucose was 441 mg/dL versus 669 mg/dL (P = .14), respectively. Serum osmolality on admission was 314 mmol/kg in 2019 versus 335 mmol/kg in 2020 (P = .19).

“Clinically speaking the differences in the lab values were significant, but we did not have enough numbers ... to see a statistically significant difference. I think by looking at more centers, our site likely represents a microcosm of what is happening across the country,” Dr. Hsia said.

In 2019, 7 of the 8 children were African American, as were 16 of the 17 children in 2020. The other single child in each group was White.

Dr. Hsia said: “Larger studies that include more patients are needed to confirm our initial findings. More research is needed to understand why this increasing trend of type 2 diabetes diagnoses in children may be occurring [and] to better understand how stay-at-home orders and other restrictions due to COVID-19 have worsened risk factors for type 2 diabetes.”

“These include decreased physical activity, more screen time, disturbed sleep, and increased intake of processed foods, which can all lead to weight gain,” he concluded.

Dr. Marks reported receiving research support from Tandem, Dexcom, and the Cystic Fibrosis Foundation. Dr. Hsia reported no relevant financial relationships.

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

The incidence of type 2 diabetes in children appears to have doubled during the COVID-19 pandemic, data from two new U.S. studies suggest, with the lead investigator of one saying she was “surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”

Anetta_R/Thinkstock

Findings from the two separate retrospective chart reviews – one conducted in Washington, D.C., and the other in Baton Rouge, La. – were presented June 25 at the annual scientific sessions of the American Diabetes Association.

Although the two studies differed somewhat in the clinical parameters examined, both revealed a similar doubling of the rates of hospitalizations for type 2 diabetes among youth during 2020, compared with the same time period in 2019, as well as greater severity of metabolic disturbance.

And, as has been previously described with type 2 diabetes in youth, African American ethnicity predominated in both cohorts.

“Although we could not assess the cause of the increases in type 2 diabetes from our data, these disparities suggest that indirect effects of social distancing measures, including school closure and unemployment, are placing undue burden on underserved communities. Decreases in well-child care and fears of seeking medical care during the pandemic may have also contributed,” lead investigator of one of the studies, pediatric endocrinologist Brynn E. Marks, MD, Children’s National Hospital, Washington, said in an interview.
 

More hospitalizations, racial disparities aggravated by COVID-19

Lead author of the other study, Daniel S. Hsia, MD, Pennington Biomedical Research Center, Baton Rouge, said in an interview: “Since the pandemic, our data suggest that more children may be diagnosed with type 2 diabetes and may require hospitalization when they are diagnosed. Looking at both datasets, there appears to be a racial disparity in type 2 diabetes diagnoses that has only been exacerbated by the COVID-19 pandemic.”

Of concern, Dr. Hsia said, “The incidence rate of type 2 diabetes in children was already on the rise before the pandemic. While there may be a brief leveling off now that children are getting regular health care and going back to school in person, I believe these rates will continue to rise especially in light of the childhood obesity rates not improving.”

Their dataset captured all youth who were newly diagnosed with type 2 diabetes during the first full year of the COVID-19 pandemic, from March 11, 2020, to March 10, 2021, and compared those data with the time period from March 11, 2019, to March 10, 2020.

During the pandemic, the number of cases of type 2 diabetes increased by 182%, from 50 in 2019 to 141 in 2020. The average age at diagnosis was about 14 years in both time periods.

In the prepandemic period, 18 (36%) diagnosed with type 2 diabetes required inpatient admission, compared with 85 (60.3%) during the pandemic. At Children’s National, youth with suspected new-onset type 2 diabetes aren’t typically hospitalized unless they have severe hyperglycemia, ketosis, or are unable to schedule urgent outpatient follow-up, Dr. Marks noted.

The proportions of youth with new-onset type 2 diabetes who presented in diabetic ketoacidosis (DKA) rose from 2 (4%) prepandemic to 33 (23.4%) during the pandemic. Presentation with hyperosmolar DKA rose from 0 to 13 (9.2%).

However, during the pandemic only five youth were actively infected with SARS-CoV-2 at the time of type 2 diabetes diagnosis among the 90 tested.

Dr. Marks said: “We believe the increase in inpatient admissions was due to more severe presentation during the pandemic. ...We were surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”
 

Shift in diagnoses to type 2 diabetes

The pandemic also appears to have shifted the proportion of youth diagnosed with type 2 diabetes, compared with type 1 diabetes. Whereas 24% of youth with new-onset diabetes prepandemic had type 2 diabetes and the rest had type 1 diabetes, during pandemic the proportion with type 2 diabetes rose to 44%.

“Rates of type 2 diabetes rose steadily at a rate of 1.45 cases per month throughout the course of the pandemic, suggesting a cumulative effect of the indirect effects of social distancing measures,” Dr. Marks said.

Furthermore, she added, whereas 60% of youth diagnosed with type 2 diabetes before the pandemic were female, the rate fell to 40% during the pandemic. This trend might be because of activity levels in that, while male adolescents are typically more active, rates of exercise fell in both sexes during the pandemic but declined more sharply in males such that activity levels between the sexes became equal.  

Although type 2 diabetes in youth has always been more common in ethnic minorities, the pandemic appears to have exacerbated these disparities.

While 58% of youth diagnosed with type 2 diabetes prepandemic identified as non-Hispanic Black, that proportion rose to 76.7% during the pandemic. Among Black youth with new-onset type 2 diabetes, 31 of 33 presented in DKA, and 12 of the 13 who presented in hyperosmolar DKA during the pandemic were Black.

“Strategies to promote health equity and address the undue burden of the COVID-19 pandemic on underserved communities must be developed to avoid worsening disparities and long-term health outcomes,” Dr. Marks said.
 

‘A microcosm’: Similar findings in a smaller population

Dr. Hsia and colleagues looked at a smaller number of patients in a shorter time period. In March–December 2019, the hospitalization rate for new-onset type 2 diabetes was 0.27% (8 out of 2,964 hospitalizations), compared with 0.62% (17 out of 2,729 hospitalizations) during the same period in 2020 (P < .048) – also more than a doubling. Age at admission, sex, and body mass index didn’t differ between the two groups.

Criteria for DKA were met by three children in 2019 versus eight in 2020, and hyperosmolar hyperglycemic syndrome in zero versus two, respectively. Mean hemoglobin A1c on admission was 12.4% in 2019 versus 13.1% in 2020 (P = .59), and mean serum glucose was 441 mg/dL versus 669 mg/dL (P = .14), respectively. Serum osmolality on admission was 314 mmol/kg in 2019 versus 335 mmol/kg in 2020 (P = .19).

“Clinically speaking the differences in the lab values were significant, but we did not have enough numbers ... to see a statistically significant difference. I think by looking at more centers, our site likely represents a microcosm of what is happening across the country,” Dr. Hsia said.

In 2019, 7 of the 8 children were African American, as were 16 of the 17 children in 2020. The other single child in each group was White.

Dr. Hsia said: “Larger studies that include more patients are needed to confirm our initial findings. More research is needed to understand why this increasing trend of type 2 diabetes diagnoses in children may be occurring [and] to better understand how stay-at-home orders and other restrictions due to COVID-19 have worsened risk factors for type 2 diabetes.”

“These include decreased physical activity, more screen time, disturbed sleep, and increased intake of processed foods, which can all lead to weight gain,” he concluded.

Dr. Marks reported receiving research support from Tandem, Dexcom, and the Cystic Fibrosis Foundation. Dr. Hsia reported no relevant financial relationships.

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

The incidence of type 2 diabetes in children appears to have doubled during the COVID-19 pandemic, data from two new U.S. studies suggest, with the lead investigator of one saying she was “surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”

Anetta_R/Thinkstock

Findings from the two separate retrospective chart reviews – one conducted in Washington, D.C., and the other in Baton Rouge, La. – were presented June 25 at the annual scientific sessions of the American Diabetes Association.

Although the two studies differed somewhat in the clinical parameters examined, both revealed a similar doubling of the rates of hospitalizations for type 2 diabetes among youth during 2020, compared with the same time period in 2019, as well as greater severity of metabolic disturbance.

And, as has been previously described with type 2 diabetes in youth, African American ethnicity predominated in both cohorts.

“Although we could not assess the cause of the increases in type 2 diabetes from our data, these disparities suggest that indirect effects of social distancing measures, including school closure and unemployment, are placing undue burden on underserved communities. Decreases in well-child care and fears of seeking medical care during the pandemic may have also contributed,” lead investigator of one of the studies, pediatric endocrinologist Brynn E. Marks, MD, Children’s National Hospital, Washington, said in an interview.
 

More hospitalizations, racial disparities aggravated by COVID-19

Lead author of the other study, Daniel S. Hsia, MD, Pennington Biomedical Research Center, Baton Rouge, said in an interview: “Since the pandemic, our data suggest that more children may be diagnosed with type 2 diabetes and may require hospitalization when they are diagnosed. Looking at both datasets, there appears to be a racial disparity in type 2 diabetes diagnoses that has only been exacerbated by the COVID-19 pandemic.”

Of concern, Dr. Hsia said, “The incidence rate of type 2 diabetes in children was already on the rise before the pandemic. While there may be a brief leveling off now that children are getting regular health care and going back to school in person, I believe these rates will continue to rise especially in light of the childhood obesity rates not improving.”

Their dataset captured all youth who were newly diagnosed with type 2 diabetes during the first full year of the COVID-19 pandemic, from March 11, 2020, to March 10, 2021, and compared those data with the time period from March 11, 2019, to March 10, 2020.

During the pandemic, the number of cases of type 2 diabetes increased by 182%, from 50 in 2019 to 141 in 2020. The average age at diagnosis was about 14 years in both time periods.

In the prepandemic period, 18 (36%) diagnosed with type 2 diabetes required inpatient admission, compared with 85 (60.3%) during the pandemic. At Children’s National, youth with suspected new-onset type 2 diabetes aren’t typically hospitalized unless they have severe hyperglycemia, ketosis, or are unable to schedule urgent outpatient follow-up, Dr. Marks noted.

The proportions of youth with new-onset type 2 diabetes who presented in diabetic ketoacidosis (DKA) rose from 2 (4%) prepandemic to 33 (23.4%) during the pandemic. Presentation with hyperosmolar DKA rose from 0 to 13 (9.2%).

However, during the pandemic only five youth were actively infected with SARS-CoV-2 at the time of type 2 diabetes diagnosis among the 90 tested.

Dr. Marks said: “We believe the increase in inpatient admissions was due to more severe presentation during the pandemic. ...We were surprised by the staggering increase in cases of type 2 diabetes ... and the increase in severity of presentation.”
 

Shift in diagnoses to type 2 diabetes

The pandemic also appears to have shifted the proportion of youth diagnosed with type 2 diabetes, compared with type 1 diabetes. Whereas 24% of youth with new-onset diabetes prepandemic had type 2 diabetes and the rest had type 1 diabetes, during pandemic the proportion with type 2 diabetes rose to 44%.

“Rates of type 2 diabetes rose steadily at a rate of 1.45 cases per month throughout the course of the pandemic, suggesting a cumulative effect of the indirect effects of social distancing measures,” Dr. Marks said.

Furthermore, she added, whereas 60% of youth diagnosed with type 2 diabetes before the pandemic were female, the rate fell to 40% during the pandemic. This trend might be because of activity levels in that, while male adolescents are typically more active, rates of exercise fell in both sexes during the pandemic but declined more sharply in males such that activity levels between the sexes became equal.  

Although type 2 diabetes in youth has always been more common in ethnic minorities, the pandemic appears to have exacerbated these disparities.

While 58% of youth diagnosed with type 2 diabetes prepandemic identified as non-Hispanic Black, that proportion rose to 76.7% during the pandemic. Among Black youth with new-onset type 2 diabetes, 31 of 33 presented in DKA, and 12 of the 13 who presented in hyperosmolar DKA during the pandemic were Black.

“Strategies to promote health equity and address the undue burden of the COVID-19 pandemic on underserved communities must be developed to avoid worsening disparities and long-term health outcomes,” Dr. Marks said.
 

‘A microcosm’: Similar findings in a smaller population

Dr. Hsia and colleagues looked at a smaller number of patients in a shorter time period. In March–December 2019, the hospitalization rate for new-onset type 2 diabetes was 0.27% (8 out of 2,964 hospitalizations), compared with 0.62% (17 out of 2,729 hospitalizations) during the same period in 2020 (P < .048) – also more than a doubling. Age at admission, sex, and body mass index didn’t differ between the two groups.

Criteria for DKA were met by three children in 2019 versus eight in 2020, and hyperosmolar hyperglycemic syndrome in zero versus two, respectively. Mean hemoglobin A1c on admission was 12.4% in 2019 versus 13.1% in 2020 (P = .59), and mean serum glucose was 441 mg/dL versus 669 mg/dL (P = .14), respectively. Serum osmolality on admission was 314 mmol/kg in 2019 versus 335 mmol/kg in 2020 (P = .19).

“Clinically speaking the differences in the lab values were significant, but we did not have enough numbers ... to see a statistically significant difference. I think by looking at more centers, our site likely represents a microcosm of what is happening across the country,” Dr. Hsia said.

In 2019, 7 of the 8 children were African American, as were 16 of the 17 children in 2020. The other single child in each group was White.

Dr. Hsia said: “Larger studies that include more patients are needed to confirm our initial findings. More research is needed to understand why this increasing trend of type 2 diabetes diagnoses in children may be occurring [and] to better understand how stay-at-home orders and other restrictions due to COVID-19 have worsened risk factors for type 2 diabetes.”

“These include decreased physical activity, more screen time, disturbed sleep, and increased intake of processed foods, which can all lead to weight gain,” he concluded.

Dr. Marks reported receiving research support from Tandem, Dexcom, and the Cystic Fibrosis Foundation. Dr. Hsia reported no relevant financial relationships.

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

Tirzepatide, a novel “twincretin” agent, was superior to 1-mg semaglutide treatments for reducing both hemoglobin A1c levels and body weight in patients with type 2 diabetes in a pivotal, 40-week, head-to-head trial with nearly 1,900 randomized patients, one of four positive pivotal trial results reported for tirzepatide at the annual scientific sessions of the American Diabetes Association.

“Across all four studies we see a significant and clinically meaningful decrease in A1c, and robust weight loss. The results exceeded our expectations” for both these outcomes, said Laura Fernández Landó, MD, senior medical director for tirzepatide at Lilly, the company developing the agent, and a coauthor on the semaglutide comparison study as well as on other tirzepatide reports at the meeting.

“This opens up a new avenue for results in diabetes therapy,” Jens Juul Holst, MD, remarked in a press conference.

SURPASS-2 compared three different tirzepatide doses delivered once weekly by subcutaneous injection against a 1-mg weekly, subcutaneous dose of semaglutide (Ozempic) in 1,879 adults who had been diagnosed with type 2 diabetes for an average of almost 9 years. All patients were already on metformin treatment that had proved inadequate for controlling their hyperglycemia; enrolled patients had an average A1c of 8.28%. The trial’s primary endpoint was change from baseline in A1c levels after 40 weeks.
 

Significant differences at each dose level

Patients on each of the three tirzepatide doses – 5 mg, 10 mg, or 15 mg once weekly – showed dose-dependent reductions in A1c that, for each dose, were significantly better than the reduction achieved with semaglutide. The highest tirzepatide dose reduced A1c levels by an average of 0.45% more than what semaglutide achieved, reported first author Juan P. Frias, MD; Dr. Landó; and their coauthors.

One key secondary endpoint was weight reduction, and each of the three tirzepatide doses again produced significant incremental loss beyond what semaglutide produced. The 5-mg weekly dose of tirzepatide produced an average 1.9-kg additional weight loss, compared with semaglutide, while the 15-mg dose resulted in an average 5.5-kg loss beyond what semaglutide achieved and a total average weight loss of 11.2 kg from baseline.

The study’s additional key secondary endpoints, the percentages of patients reaching an A1c of less than 7%, and less than 5.7%, also showed significantly better numbers with tirzepatide. The highest tirzepatide dose pushed 86% of patients below the 7% mark, compared with 79% on semaglutide, and the top tirzepatide dose resulted in 46% of patients getting their A1c below 5.7%, compared with 19% of patients on semaglutide.

The findings are “stunning, I must stay, and those results included that up to half of the patients treated with high doses of tirzepatide may reach A1c levels of less than 5.7%, which is really, really unheard of,” said Dr. Holst, professor of endocrinology and metabolism at the University of Copenhagen. Along with the “weight losses at the same time of up to 12% in that patient group, we are seeing some completely unexpected and really shocking and wonderful new advances in the therapy,” added Dr. Holst.

The safety profile of tirzepatide was roughly similar to semaglutide’s and to that other agents in the glucagonlike peptide-1 receptor agonist (GLP-1 RA) class. Concurrently with the report at the meeting, the results also appeared in an article published online in the New England Journal of Medicine.
 

An ‘impressive’ weight loss effect

Weight loss on tirzepatide was “impressive,” commented Katherine R. Tuttle, MD, a nephrologist affiliated with the University of Washington and executive director for research at Providence Health Care in Spokane, Wash. Another striking feature of tirzepatide’s weight-loss effect was that it did not plateau during the 40 weeks of the study, Dr. Tuttle noted in an accompanying editorial that accompanied the published report, a finding that suggests the potential for additional weight loss from continued treatment .

“The weight loss is remarkable,” commented Rodolfo J. Galindo, MD, an endocrinologist at Emory University, Atlanta. While incremental reduction of A1c on the order of less than 0.5% is helpful, incremental weight loss of more than 10 lbs on tirzepatide, compared with semaglutide “will likely be a tie-breaker” for many clinicians and patients to favor tirzepatide over semaglutide or another GLP-1 RA agent, he said in an interview. Dr. Galindo also cited other important factors that he predicted will drive decisions on using tirzepatide or a GLP-1 RA once tirzepatide reaches the U.S. market: relative cost, access, and tolerability.
 

The important issue of dose

But the edge that tirzepatide showed over semaglutide for weight loss did not occur on a completely level playing field. The 1 mg/week dose of semaglutide used as the comparator in SURPASS-2 was the maximum dose available at the time the study began, but in June 2021 the Food and Drug Administration approved a 2.4 mg/week dose (Wegovy) labeled specifically for weight loss. Dr. Tuttle cited the limitation this introduces in her editorial.

“The dose issue is important,” she wrote. The doses of tirzepatide and semaglutide compared in SURPASS-2 “were not comparable in terms of weight outcomes” given that prior evidence showed that the 2.4 mg/week semaglutide dose is more appropriate for weight loss.

Dr. Tuttle also cited other factors to consider when assessing tirzepatide compared with agents in the GLP-1 RA class.

Several GLP-1 RA agents, including semaglutide, have proven efficacy for reducing rates of atherosclerotic cardiovascular events and albuminuria, and they also slow decline in kidney function and progression of diabetic kidney disease. No details on the renal effects of tirzepatide appeared in the SURPASS-2 report. A press release from Lilly in May 2021 briefly mentioned results from a meta-analysis of several clinical studies of tirzepatide that showed a nonsignificant effect from tirzepatide on the incidence of major cardiovascular adverse events (death from cardiovascular or undetermined causes, MI, stroke, and hospitalization for unstable angina) relative to comparator groups. Results from a dedicated cardiovascular outcomes trial in high-risk patients treated with tirzepatide, SURPASS-CVOT, are not expected until 2024.

A further limitation of SURPASS-2 was the demographics of the enrolled population, which had a low (0.4%) enrollment rate of Black patients, and a high proportion (70%) of Hispanic patients, Dr. Tuttle observed.
 

Low rates of hypoglycemia

Another notable finding from SURPASS-2 was the low incidence of clinically significant hypoglycemic events (blood glucose levels less than 54 mg/dL), which occurred in 0.2%-1.7% of patients on tirzepatide, depending on their dose, and in 0.4% of patients on semaglutide. Two patients in the tirzepatide cohort had severe hypoglycemia.

These numbers are reassuring, said Dr. Galindo, and reflect the safety of tirzepatide’s dual, incretin-like mechanisms of action that make it a “twincretin.” The molecule acts as both a GLP-1 RA, and as glucose-dependent insulinotropic polypeptide, an incretin that stimulates insulin release when blood sugar is high but also increases glucagon levels when blood sugar levels are normal or low. This dual action may help explain the apparent increased potency tirzepatide showed for both A1c reduction and weight loss, compared with semaglutide, which acts only as a GLP-1 RA.

Some experts have cited the uncertainty introduced by the open-label design of SURPASS-2, a decision necessitated by the distinctly different delivery devices used for tirzepatide and semaglutide, explained Dr. Landó. But she highlighted that double blinding applied to the three different tirzepatide dosages tested in the trial. Dr. Landó said that Lilly plans to seek FDA approval for all three tested tirzepatide doses to give clinicians and patients flexibility in applying the treatment.

SURPASS-2 used a prolonged dose-escalation protocol designed to minimize gastrointestinal adverse effects that started patients on a 2.5 mg weekly dose that then increased by 2.5 mg increments every 4 weeks until patients reached their assigned target dose. This meant that patients did not begin receiving the 15-mg/week dose until halfway through the trial.
 

Several more tirzepatide trials

Reports from two other pivotal trials for tirzepatide also appeared as posters at the meeting. SURPASS-5 compared tirzepatide with placebo in 475 patients inadequately controlled with titrated insulin glargine (Lantus). SURPASS-3 randomized 1,444 patients to tirzepatide or titrated insulin degludec (Tresiba). In both studies treatment with tirzepatide led to significantly better reductions in A1c and in weight loss than the comparator treatments. Results from a third pivotal trial, SURPASS-1 which compared tirzepatide against placebo in 478 treatment-naive patients, will come in a report scheduled for the second day of the meeting.

The results from all the recent tirzepatide trials show a consistent benefit across the continuum of patients with type 2 diabetes regardless of whether it’s recent onset or well-established disease, said Dr. Landó.

The SURPASS studies were sponsored by Lilly, the company developing tirzepatide, and the reports include several authors who are Lilly employees. Dr. Landó is a Lilly employee and stockholder. Dr. Tuttle has been a consultant to Lilly and to Novo Nordisk, the company that markets semaglutide, as well as to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, and Janssen. She has also received travel expenses from Kyokawa Hakko Kirin, and research funding from Bayer, Goldfinch Bio, and Lilly. Dr. Galindo has been a consultant to Lilly and to Novo Nordisk, as well as to Abbott Diabetes Care, Sanofi, Valeritas, and Weight Watchers, and his institution has received grant support on his behalf from Lilly, Novo Nordisk and Dexcom. Dr. Holst had no disclosures.

[email protected]

Tirzepatide, a novel “twincretin” agent, was superior to 1-mg semaglutide treatments for reducing both hemoglobin A1c levels and body weight in patients with type 2 diabetes in a pivotal, 40-week, head-to-head trial with nearly 1,900 randomized patients, one of four positive pivotal trial results reported for tirzepatide at the annual scientific sessions of the American Diabetes Association.

“Across all four studies we see a significant and clinically meaningful decrease in A1c, and robust weight loss. The results exceeded our expectations” for both these outcomes, said Laura Fernández Landó, MD, senior medical director for tirzepatide at Lilly, the company developing the agent, and a coauthor on the semaglutide comparison study as well as on other tirzepatide reports at the meeting.

“This opens up a new avenue for results in diabetes therapy,” Jens Juul Holst, MD, remarked in a press conference.

SURPASS-2 compared three different tirzepatide doses delivered once weekly by subcutaneous injection against a 1-mg weekly, subcutaneous dose of semaglutide (Ozempic) in 1,879 adults who had been diagnosed with type 2 diabetes for an average of almost 9 years. All patients were already on metformin treatment that had proved inadequate for controlling their hyperglycemia; enrolled patients had an average A1c of 8.28%. The trial’s primary endpoint was change from baseline in A1c levels after 40 weeks.
 

Significant differences at each dose level

Patients on each of the three tirzepatide doses – 5 mg, 10 mg, or 15 mg once weekly – showed dose-dependent reductions in A1c that, for each dose, were significantly better than the reduction achieved with semaglutide. The highest tirzepatide dose reduced A1c levels by an average of 0.45% more than what semaglutide achieved, reported first author Juan P. Frias, MD; Dr. Landó; and their coauthors.

One key secondary endpoint was weight reduction, and each of the three tirzepatide doses again produced significant incremental loss beyond what semaglutide produced. The 5-mg weekly dose of tirzepatide produced an average 1.9-kg additional weight loss, compared with semaglutide, while the 15-mg dose resulted in an average 5.5-kg loss beyond what semaglutide achieved and a total average weight loss of 11.2 kg from baseline.

The study’s additional key secondary endpoints, the percentages of patients reaching an A1c of less than 7%, and less than 5.7%, also showed significantly better numbers with tirzepatide. The highest tirzepatide dose pushed 86% of patients below the 7% mark, compared with 79% on semaglutide, and the top tirzepatide dose resulted in 46% of patients getting their A1c below 5.7%, compared with 19% of patients on semaglutide.

The findings are “stunning, I must stay, and those results included that up to half of the patients treated with high doses of tirzepatide may reach A1c levels of less than 5.7%, which is really, really unheard of,” said Dr. Holst, professor of endocrinology and metabolism at the University of Copenhagen. Along with the “weight losses at the same time of up to 12% in that patient group, we are seeing some completely unexpected and really shocking and wonderful new advances in the therapy,” added Dr. Holst.

The safety profile of tirzepatide was roughly similar to semaglutide’s and to that other agents in the glucagonlike peptide-1 receptor agonist (GLP-1 RA) class. Concurrently with the report at the meeting, the results also appeared in an article published online in the New England Journal of Medicine.
 

An ‘impressive’ weight loss effect

Weight loss on tirzepatide was “impressive,” commented Katherine R. Tuttle, MD, a nephrologist affiliated with the University of Washington and executive director for research at Providence Health Care in Spokane, Wash. Another striking feature of tirzepatide’s weight-loss effect was that it did not plateau during the 40 weeks of the study, Dr. Tuttle noted in an accompanying editorial that accompanied the published report, a finding that suggests the potential for additional weight loss from continued treatment .

“The weight loss is remarkable,” commented Rodolfo J. Galindo, MD, an endocrinologist at Emory University, Atlanta. While incremental reduction of A1c on the order of less than 0.5% is helpful, incremental weight loss of more than 10 lbs on tirzepatide, compared with semaglutide “will likely be a tie-breaker” for many clinicians and patients to favor tirzepatide over semaglutide or another GLP-1 RA agent, he said in an interview. Dr. Galindo also cited other important factors that he predicted will drive decisions on using tirzepatide or a GLP-1 RA once tirzepatide reaches the U.S. market: relative cost, access, and tolerability.
 

The important issue of dose

But the edge that tirzepatide showed over semaglutide for weight loss did not occur on a completely level playing field. The 1 mg/week dose of semaglutide used as the comparator in SURPASS-2 was the maximum dose available at the time the study began, but in June 2021 the Food and Drug Administration approved a 2.4 mg/week dose (Wegovy) labeled specifically for weight loss. Dr. Tuttle cited the limitation this introduces in her editorial.

“The dose issue is important,” she wrote. The doses of tirzepatide and semaglutide compared in SURPASS-2 “were not comparable in terms of weight outcomes” given that prior evidence showed that the 2.4 mg/week semaglutide dose is more appropriate for weight loss.

Dr. Tuttle also cited other factors to consider when assessing tirzepatide compared with agents in the GLP-1 RA class.

Several GLP-1 RA agents, including semaglutide, have proven efficacy for reducing rates of atherosclerotic cardiovascular events and albuminuria, and they also slow decline in kidney function and progression of diabetic kidney disease. No details on the renal effects of tirzepatide appeared in the SURPASS-2 report. A press release from Lilly in May 2021 briefly mentioned results from a meta-analysis of several clinical studies of tirzepatide that showed a nonsignificant effect from tirzepatide on the incidence of major cardiovascular adverse events (death from cardiovascular or undetermined causes, MI, stroke, and hospitalization for unstable angina) relative to comparator groups. Results from a dedicated cardiovascular outcomes trial in high-risk patients treated with tirzepatide, SURPASS-CVOT, are not expected until 2024.

A further limitation of SURPASS-2 was the demographics of the enrolled population, which had a low (0.4%) enrollment rate of Black patients, and a high proportion (70%) of Hispanic patients, Dr. Tuttle observed.
 

Low rates of hypoglycemia

Another notable finding from SURPASS-2 was the low incidence of clinically significant hypoglycemic events (blood glucose levels less than 54 mg/dL), which occurred in 0.2%-1.7% of patients on tirzepatide, depending on their dose, and in 0.4% of patients on semaglutide. Two patients in the tirzepatide cohort had severe hypoglycemia.

These numbers are reassuring, said Dr. Galindo, and reflect the safety of tirzepatide’s dual, incretin-like mechanisms of action that make it a “twincretin.” The molecule acts as both a GLP-1 RA, and as glucose-dependent insulinotropic polypeptide, an incretin that stimulates insulin release when blood sugar is high but also increases glucagon levels when blood sugar levels are normal or low. This dual action may help explain the apparent increased potency tirzepatide showed for both A1c reduction and weight loss, compared with semaglutide, which acts only as a GLP-1 RA.

Some experts have cited the uncertainty introduced by the open-label design of SURPASS-2, a decision necessitated by the distinctly different delivery devices used for tirzepatide and semaglutide, explained Dr. Landó. But she highlighted that double blinding applied to the three different tirzepatide dosages tested in the trial. Dr. Landó said that Lilly plans to seek FDA approval for all three tested tirzepatide doses to give clinicians and patients flexibility in applying the treatment.

SURPASS-2 used a prolonged dose-escalation protocol designed to minimize gastrointestinal adverse effects that started patients on a 2.5 mg weekly dose that then increased by 2.5 mg increments every 4 weeks until patients reached their assigned target dose. This meant that patients did not begin receiving the 15-mg/week dose until halfway through the trial.
 

Several more tirzepatide trials

Reports from two other pivotal trials for tirzepatide also appeared as posters at the meeting. SURPASS-5 compared tirzepatide with placebo in 475 patients inadequately controlled with titrated insulin glargine (Lantus). SURPASS-3 randomized 1,444 patients to tirzepatide or titrated insulin degludec (Tresiba). In both studies treatment with tirzepatide led to significantly better reductions in A1c and in weight loss than the comparator treatments. Results from a third pivotal trial, SURPASS-1 which compared tirzepatide against placebo in 478 treatment-naive patients, will come in a report scheduled for the second day of the meeting.

The results from all the recent tirzepatide trials show a consistent benefit across the continuum of patients with type 2 diabetes regardless of whether it’s recent onset or well-established disease, said Dr. Landó.

The SURPASS studies were sponsored by Lilly, the company developing tirzepatide, and the reports include several authors who are Lilly employees. Dr. Landó is a Lilly employee and stockholder. Dr. Tuttle has been a consultant to Lilly and to Novo Nordisk, the company that markets semaglutide, as well as to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, and Janssen. She has also received travel expenses from Kyokawa Hakko Kirin, and research funding from Bayer, Goldfinch Bio, and Lilly. Dr. Galindo has been a consultant to Lilly and to Novo Nordisk, as well as to Abbott Diabetes Care, Sanofi, Valeritas, and Weight Watchers, and his institution has received grant support on his behalf from Lilly, Novo Nordisk and Dexcom. Dr. Holst had no disclosures.

[email protected]

Tirzepatide, a novel “twincretin” agent, was superior to 1-mg semaglutide treatments for reducing both hemoglobin A1c levels and body weight in patients with type 2 diabetes in a pivotal, 40-week, head-to-head trial with nearly 1,900 randomized patients, one of four positive pivotal trial results reported for tirzepatide at the annual scientific sessions of the American Diabetes Association.

“Across all four studies we see a significant and clinically meaningful decrease in A1c, and robust weight loss. The results exceeded our expectations” for both these outcomes, said Laura Fernández Landó, MD, senior medical director for tirzepatide at Lilly, the company developing the agent, and a coauthor on the semaglutide comparison study as well as on other tirzepatide reports at the meeting.

“This opens up a new avenue for results in diabetes therapy,” Jens Juul Holst, MD, remarked in a press conference.

SURPASS-2 compared three different tirzepatide doses delivered once weekly by subcutaneous injection against a 1-mg weekly, subcutaneous dose of semaglutide (Ozempic) in 1,879 adults who had been diagnosed with type 2 diabetes for an average of almost 9 years. All patients were already on metformin treatment that had proved inadequate for controlling their hyperglycemia; enrolled patients had an average A1c of 8.28%. The trial’s primary endpoint was change from baseline in A1c levels after 40 weeks.
 

Significant differences at each dose level

Patients on each of the three tirzepatide doses – 5 mg, 10 mg, or 15 mg once weekly – showed dose-dependent reductions in A1c that, for each dose, were significantly better than the reduction achieved with semaglutide. The highest tirzepatide dose reduced A1c levels by an average of 0.45% more than what semaglutide achieved, reported first author Juan P. Frias, MD; Dr. Landó; and their coauthors.

One key secondary endpoint was weight reduction, and each of the three tirzepatide doses again produced significant incremental loss beyond what semaglutide produced. The 5-mg weekly dose of tirzepatide produced an average 1.9-kg additional weight loss, compared with semaglutide, while the 15-mg dose resulted in an average 5.5-kg loss beyond what semaglutide achieved and a total average weight loss of 11.2 kg from baseline.

The study’s additional key secondary endpoints, the percentages of patients reaching an A1c of less than 7%, and less than 5.7%, also showed significantly better numbers with tirzepatide. The highest tirzepatide dose pushed 86% of patients below the 7% mark, compared with 79% on semaglutide, and the top tirzepatide dose resulted in 46% of patients getting their A1c below 5.7%, compared with 19% of patients on semaglutide.

The findings are “stunning, I must stay, and those results included that up to half of the patients treated with high doses of tirzepatide may reach A1c levels of less than 5.7%, which is really, really unheard of,” said Dr. Holst, professor of endocrinology and metabolism at the University of Copenhagen. Along with the “weight losses at the same time of up to 12% in that patient group, we are seeing some completely unexpected and really shocking and wonderful new advances in the therapy,” added Dr. Holst.

The safety profile of tirzepatide was roughly similar to semaglutide’s and to that other agents in the glucagonlike peptide-1 receptor agonist (GLP-1 RA) class. Concurrently with the report at the meeting, the results also appeared in an article published online in the New England Journal of Medicine.
 

An ‘impressive’ weight loss effect

Weight loss on tirzepatide was “impressive,” commented Katherine R. Tuttle, MD, a nephrologist affiliated with the University of Washington and executive director for research at Providence Health Care in Spokane, Wash. Another striking feature of tirzepatide’s weight-loss effect was that it did not plateau during the 40 weeks of the study, Dr. Tuttle noted in an accompanying editorial that accompanied the published report, a finding that suggests the potential for additional weight loss from continued treatment .

“The weight loss is remarkable,” commented Rodolfo J. Galindo, MD, an endocrinologist at Emory University, Atlanta. While incremental reduction of A1c on the order of less than 0.5% is helpful, incremental weight loss of more than 10 lbs on tirzepatide, compared with semaglutide “will likely be a tie-breaker” for many clinicians and patients to favor tirzepatide over semaglutide or another GLP-1 RA agent, he said in an interview. Dr. Galindo also cited other important factors that he predicted will drive decisions on using tirzepatide or a GLP-1 RA once tirzepatide reaches the U.S. market: relative cost, access, and tolerability.
 

The important issue of dose

But the edge that tirzepatide showed over semaglutide for weight loss did not occur on a completely level playing field. The 1 mg/week dose of semaglutide used as the comparator in SURPASS-2 was the maximum dose available at the time the study began, but in June 2021 the Food and Drug Administration approved a 2.4 mg/week dose (Wegovy) labeled specifically for weight loss. Dr. Tuttle cited the limitation this introduces in her editorial.

“The dose issue is important,” she wrote. The doses of tirzepatide and semaglutide compared in SURPASS-2 “were not comparable in terms of weight outcomes” given that prior evidence showed that the 2.4 mg/week semaglutide dose is more appropriate for weight loss.

Dr. Tuttle also cited other factors to consider when assessing tirzepatide compared with agents in the GLP-1 RA class.

Several GLP-1 RA agents, including semaglutide, have proven efficacy for reducing rates of atherosclerotic cardiovascular events and albuminuria, and they also slow decline in kidney function and progression of diabetic kidney disease. No details on the renal effects of tirzepatide appeared in the SURPASS-2 report. A press release from Lilly in May 2021 briefly mentioned results from a meta-analysis of several clinical studies of tirzepatide that showed a nonsignificant effect from tirzepatide on the incidence of major cardiovascular adverse events (death from cardiovascular or undetermined causes, MI, stroke, and hospitalization for unstable angina) relative to comparator groups. Results from a dedicated cardiovascular outcomes trial in high-risk patients treated with tirzepatide, SURPASS-CVOT, are not expected until 2024.

A further limitation of SURPASS-2 was the demographics of the enrolled population, which had a low (0.4%) enrollment rate of Black patients, and a high proportion (70%) of Hispanic patients, Dr. Tuttle observed.
 

Low rates of hypoglycemia

Another notable finding from SURPASS-2 was the low incidence of clinically significant hypoglycemic events (blood glucose levels less than 54 mg/dL), which occurred in 0.2%-1.7% of patients on tirzepatide, depending on their dose, and in 0.4% of patients on semaglutide. Two patients in the tirzepatide cohort had severe hypoglycemia.

These numbers are reassuring, said Dr. Galindo, and reflect the safety of tirzepatide’s dual, incretin-like mechanisms of action that make it a “twincretin.” The molecule acts as both a GLP-1 RA, and as glucose-dependent insulinotropic polypeptide, an incretin that stimulates insulin release when blood sugar is high but also increases glucagon levels when blood sugar levels are normal or low. This dual action may help explain the apparent increased potency tirzepatide showed for both A1c reduction and weight loss, compared with semaglutide, which acts only as a GLP-1 RA.

Some experts have cited the uncertainty introduced by the open-label design of SURPASS-2, a decision necessitated by the distinctly different delivery devices used for tirzepatide and semaglutide, explained Dr. Landó. But she highlighted that double blinding applied to the three different tirzepatide dosages tested in the trial. Dr. Landó said that Lilly plans to seek FDA approval for all three tested tirzepatide doses to give clinicians and patients flexibility in applying the treatment.

SURPASS-2 used a prolonged dose-escalation protocol designed to minimize gastrointestinal adverse effects that started patients on a 2.5 mg weekly dose that then increased by 2.5 mg increments every 4 weeks until patients reached their assigned target dose. This meant that patients did not begin receiving the 15-mg/week dose until halfway through the trial.
 

Several more tirzepatide trials

Reports from two other pivotal trials for tirzepatide also appeared as posters at the meeting. SURPASS-5 compared tirzepatide with placebo in 475 patients inadequately controlled with titrated insulin glargine (Lantus). SURPASS-3 randomized 1,444 patients to tirzepatide or titrated insulin degludec (Tresiba). In both studies treatment with tirzepatide led to significantly better reductions in A1c and in weight loss than the comparator treatments. Results from a third pivotal trial, SURPASS-1 which compared tirzepatide against placebo in 478 treatment-naive patients, will come in a report scheduled for the second day of the meeting.

The results from all the recent tirzepatide trials show a consistent benefit across the continuum of patients with type 2 diabetes regardless of whether it’s recent onset or well-established disease, said Dr. Landó.

The SURPASS studies were sponsored by Lilly, the company developing tirzepatide, and the reports include several authors who are Lilly employees. Dr. Landó is a Lilly employee and stockholder. Dr. Tuttle has been a consultant to Lilly and to Novo Nordisk, the company that markets semaglutide, as well as to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, and Janssen. She has also received travel expenses from Kyokawa Hakko Kirin, and research funding from Bayer, Goldfinch Bio, and Lilly. Dr. Galindo has been a consultant to Lilly and to Novo Nordisk, as well as to Abbott Diabetes Care, Sanofi, Valeritas, and Weight Watchers, and his institution has received grant support on his behalf from Lilly, Novo Nordisk and Dexcom. Dr. Holst had no disclosures.

[email protected]

Unmanaged diabetes and high blood glucose levels are linked to more severe COVID-19 and worse rates of recovery, according to results of a retrospective study.

Patients not managing their diabetes with medication had more severe COVID-19 and length of hospitalization, compared with those who were taking medication, investigator Sudip Bajpeyi, PhD, said at the annual scientific sessions of the American Diabetes Association.

In addition, patients with higher blood glucose levels had more severe COVID-19 and longer hospital stays.

Those findings underscore the need to assess, monitor, and control blood glucose, especially in vulnerable populations, said Dr. Bajpeyi, director of the Metabolic, Nutrition, and Exercise Research Laboratory in the University of Texas, El Paso, who added that nearly 90% of the study subjects were Hispanic.

“As public health decisions are made, we think fasting blood glucose should be considered in the treatment of hospitalized COVID-19 patients,” he said in a press conference.
 

Links between diabetes and COVID-19

There are now many reports in medical literature that link diabetes to increased risk of COVID-19 severity, according to Ali Mossayebi, a master’s student who worked on the study. However, there are fewer studies that have looked specifically at the implications of poor diabetes management or acute glycemic control, the investigators said.

It’s known that poorly controlled diabetes can have severe health consequences, including higher risks for life-threatening comorbidities, they added.

Their retrospective study focused on medical records from 364 patients with COVID-19 admitted to a medical center in El Paso. Their mean age was 60 years, and their mean body mass index was 30.3 kg/m²; 87% were Hispanic.

Acute glycemic control was assessed by fasting blood glucose at the time of hospitalization, while chronic glycemic control was assessed by hemoglobin A1c, the investigators said. Severity of COVID-19 was measured with the Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), which is based on the patient’s respiratory rate, blood pressure, and mental status.
 

Impact of unmanaged diabetes and high blood glucose

Severity of COVID-19 severity and length of hospital stay were significantly greater in patients with unmanaged diabetes, as compared with those who reported that they managed their diabetes with medication, Dr. Bajpeyi and coinvestigators found.

Among patients with unmanaged diabetes, the mean qSOFA score was 0.22, as compared with 0.44 for patients with managed diabetes. The mean length of hospital stay was 10.8 days for patients with unmanaged diabetes and 8.2 days for those with medication-managed diabetes, according to the abstract.

COVID-19 severity and hospital stay length were highest among patients with acute glycemia, the investigators further reported in an electronic poster that was part of the ADA meeting proceedings.

The mean qSOFA score was about 0.6 for patients with blood glucose levels of at least 126 mg/dL and A1c below 6.5%, and roughly 0.2 for those with normal blood glucose and normal A1c. Similarly, duration of hospital stay was significantly higher for patients with high blood glucose and A1c as compared with those with normal blood glucose and A1c.
 

Aggressive treatment needed

Findings of this study are in line with previous research showing that in-hospital hyperglycemia is a common and important marker of poor clinical outcome and mortality, with or without diabetes, according to Rodolfo J. Galindo, MD, FACE, medical chair of the hospital diabetes task force at Emory Healthcare System, Atlanta.

“These patients need aggressive treatment of hyperglycemia, regardless of the diagnosis of diabetes or A1c value,” said Dr. Galindo, who was not involved in the study. “They also need outpatient follow-up after discharge, because they may develop diabetes soon after.”

Follow-up within is important because roughly 30% of patients with stress hyperglycemia (increases in blood glucose during an acute illness) will develop diabetes within a year, according to Dr. Galindo.

“We do not know in COVID-10 patients if it is only 30%,” he said, “Our thinking in our group is that it’s probably higher.”

Dr. Bajpeyi and coauthors reported no disclosures. Dr. Galindo reported disclosures related to Abbott Diabetes, Boehringer Ingelheim International, Eli Lilly, Novo Nordisk, Sanofi US, Valeritas, and Dexcom.

Unmanaged diabetes and high blood glucose levels are linked to more severe COVID-19 and worse rates of recovery, according to results of a retrospective study.

Patients not managing their diabetes with medication had more severe COVID-19 and length of hospitalization, compared with those who were taking medication, investigator Sudip Bajpeyi, PhD, said at the annual scientific sessions of the American Diabetes Association.

In addition, patients with higher blood glucose levels had more severe COVID-19 and longer hospital stays.

Those findings underscore the need to assess, monitor, and control blood glucose, especially in vulnerable populations, said Dr. Bajpeyi, director of the Metabolic, Nutrition, and Exercise Research Laboratory in the University of Texas, El Paso, who added that nearly 90% of the study subjects were Hispanic.

“As public health decisions are made, we think fasting blood glucose should be considered in the treatment of hospitalized COVID-19 patients,” he said in a press conference.
 

Links between diabetes and COVID-19

There are now many reports in medical literature that link diabetes to increased risk of COVID-19 severity, according to Ali Mossayebi, a master’s student who worked on the study. However, there are fewer studies that have looked specifically at the implications of poor diabetes management or acute glycemic control, the investigators said.

It’s known that poorly controlled diabetes can have severe health consequences, including higher risks for life-threatening comorbidities, they added.

Their retrospective study focused on medical records from 364 patients with COVID-19 admitted to a medical center in El Paso. Their mean age was 60 years, and their mean body mass index was 30.3 kg/m²; 87% were Hispanic.

Acute glycemic control was assessed by fasting blood glucose at the time of hospitalization, while chronic glycemic control was assessed by hemoglobin A1c, the investigators said. Severity of COVID-19 was measured with the Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), which is based on the patient’s respiratory rate, blood pressure, and mental status.
 

Impact of unmanaged diabetes and high blood glucose

Severity of COVID-19 severity and length of hospital stay were significantly greater in patients with unmanaged diabetes, as compared with those who reported that they managed their diabetes with medication, Dr. Bajpeyi and coinvestigators found.

Among patients with unmanaged diabetes, the mean qSOFA score was 0.22, as compared with 0.44 for patients with managed diabetes. The mean length of hospital stay was 10.8 days for patients with unmanaged diabetes and 8.2 days for those with medication-managed diabetes, according to the abstract.

COVID-19 severity and hospital stay length were highest among patients with acute glycemia, the investigators further reported in an electronic poster that was part of the ADA meeting proceedings.

The mean qSOFA score was about 0.6 for patients with blood glucose levels of at least 126 mg/dL and A1c below 6.5%, and roughly 0.2 for those with normal blood glucose and normal A1c. Similarly, duration of hospital stay was significantly higher for patients with high blood glucose and A1c as compared with those with normal blood glucose and A1c.
 

Aggressive treatment needed

Findings of this study are in line with previous research showing that in-hospital hyperglycemia is a common and important marker of poor clinical outcome and mortality, with or without diabetes, according to Rodolfo J. Galindo, MD, FACE, medical chair of the hospital diabetes task force at Emory Healthcare System, Atlanta.

“These patients need aggressive treatment of hyperglycemia, regardless of the diagnosis of diabetes or A1c value,” said Dr. Galindo, who was not involved in the study. “They also need outpatient follow-up after discharge, because they may develop diabetes soon after.”

Follow-up within is important because roughly 30% of patients with stress hyperglycemia (increases in blood glucose during an acute illness) will develop diabetes within a year, according to Dr. Galindo.

“We do not know in COVID-10 patients if it is only 30%,” he said, “Our thinking in our group is that it’s probably higher.”

Dr. Bajpeyi and coauthors reported no disclosures. Dr. Galindo reported disclosures related to Abbott Diabetes, Boehringer Ingelheim International, Eli Lilly, Novo Nordisk, Sanofi US, Valeritas, and Dexcom.

Unmanaged diabetes and high blood glucose levels are linked to more severe COVID-19 and worse rates of recovery, according to results of a retrospective study.

Patients not managing their diabetes with medication had more severe COVID-19 and length of hospitalization, compared with those who were taking medication, investigator Sudip Bajpeyi, PhD, said at the annual scientific sessions of the American Diabetes Association.

In addition, patients with higher blood glucose levels had more severe COVID-19 and longer hospital stays.

Those findings underscore the need to assess, monitor, and control blood glucose, especially in vulnerable populations, said Dr. Bajpeyi, director of the Metabolic, Nutrition, and Exercise Research Laboratory in the University of Texas, El Paso, who added that nearly 90% of the study subjects were Hispanic.

“As public health decisions are made, we think fasting blood glucose should be considered in the treatment of hospitalized COVID-19 patients,” he said in a press conference.
 

Links between diabetes and COVID-19

There are now many reports in medical literature that link diabetes to increased risk of COVID-19 severity, according to Ali Mossayebi, a master’s student who worked on the study. However, there are fewer studies that have looked specifically at the implications of poor diabetes management or acute glycemic control, the investigators said.

It’s known that poorly controlled diabetes can have severe health consequences, including higher risks for life-threatening comorbidities, they added.

Their retrospective study focused on medical records from 364 patients with COVID-19 admitted to a medical center in El Paso. Their mean age was 60 years, and their mean body mass index was 30.3 kg/m²; 87% were Hispanic.

Acute glycemic control was assessed by fasting blood glucose at the time of hospitalization, while chronic glycemic control was assessed by hemoglobin A1c, the investigators said. Severity of COVID-19 was measured with the Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), which is based on the patient’s respiratory rate, blood pressure, and mental status.
 

Impact of unmanaged diabetes and high blood glucose

Severity of COVID-19 severity and length of hospital stay were significantly greater in patients with unmanaged diabetes, as compared with those who reported that they managed their diabetes with medication, Dr. Bajpeyi and coinvestigators found.

Among patients with unmanaged diabetes, the mean qSOFA score was 0.22, as compared with 0.44 for patients with managed diabetes. The mean length of hospital stay was 10.8 days for patients with unmanaged diabetes and 8.2 days for those with medication-managed diabetes, according to the abstract.

COVID-19 severity and hospital stay length were highest among patients with acute glycemia, the investigators further reported in an electronic poster that was part of the ADA meeting proceedings.

The mean qSOFA score was about 0.6 for patients with blood glucose levels of at least 126 mg/dL and A1c below 6.5%, and roughly 0.2 for those with normal blood glucose and normal A1c. Similarly, duration of hospital stay was significantly higher for patients with high blood glucose and A1c as compared with those with normal blood glucose and A1c.
 

Aggressive treatment needed

Findings of this study are in line with previous research showing that in-hospital hyperglycemia is a common and important marker of poor clinical outcome and mortality, with or without diabetes, according to Rodolfo J. Galindo, MD, FACE, medical chair of the hospital diabetes task force at Emory Healthcare System, Atlanta.

“These patients need aggressive treatment of hyperglycemia, regardless of the diagnosis of diabetes or A1c value,” said Dr. Galindo, who was not involved in the study. “They also need outpatient follow-up after discharge, because they may develop diabetes soon after.”

Follow-up within is important because roughly 30% of patients with stress hyperglycemia (increases in blood glucose during an acute illness) will develop diabetes within a year, according to Dr. Galindo.

“We do not know in COVID-10 patients if it is only 30%,” he said, “Our thinking in our group is that it’s probably higher.”

Dr. Bajpeyi and coauthors reported no disclosures. Dr. Galindo reported disclosures related to Abbott Diabetes, Boehringer Ingelheim International, Eli Lilly, Novo Nordisk, Sanofi US, Valeritas, and Dexcom.