Diabetes

BARCELONA – Obesity, more so than having a poor lifestyle, significantly raised the odds of developing type 2 diabetes, independent of individuals’ genetic susceptibility, according to data from a Danish population-based, case-cohort study.

In fact, having a body mass index (BMI) of more than 30 kg/m2 was linked with a 480% risk of incident type 2 diabetes, compared with being of normal weight (BMI, 18.5-24.9 kg/m2). The 95% confidence interval was 5.16-6.55. Being overweight (BMI, 25-29.9 kg/m2) also carried a 100% increased risk of type 2 diabetes (hazard ratio, 2.37; 95% CI, 2.15-2.62).

Having an unfavorable lifestyle – which was defined as having no or only one of several healthy-living characteristics, from not smoking and moderating alcohol use to eating a well-balanced, nutritious diet and exercising regularly – increased the risk of diabetes by 18%, compared with having a favorable lifestyle (HR, 1.18; 95% CI, 1.06-1.30).

Individuals with a high genetic risk score (GRS) had a 100% increased risk of developing the disease versus those with a low GRS (HR, 2.0; 95% CI, 1.1-1.3).

“High genetic risk, obesity, and [an] unfavorable lifestyle increase the individual-level risk of incident type 2 diabetes,” Hermina Jakupovic and associates reported in a poster presentation at the annual meeting of the European Association for the Study of Diabetes. Their results suggest that “the effect of obesity on type 2 diabetes risk is dominant over other risk factors, highlighting the importance of weight management in type 2 diabetes prevention.”

Ms. Jakupovic, a PhD student at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, and coauthors examined data on 9,555 participants of the Diet, Cancer, and Health cohort, a large, prospective study that has been running since the early 1990s.

Around half of the study sample were women and the mean age was 52 years. Just over one-fifth (22.8%) were obese, 43% were overweight, and the remaining 35.2% were of normal weight. A quarter (25.4%) had an unfavorable lifestyle, 40% a favorable lifestyle, and the remainder an “intermediate” lifestyle. Over a follow-up of almost 15 years, nearly half (49.5%) developed type 2 diabetes.

Genetic risk was assessed by a GRS comprising 193 genetic variants known to be strongly associated with type 2 diabetes, Ms. Jakupovic explained, adding that, using the GRS, patients were categorized into being at low (the lowest 20%), intermediate (middle 60%) and high risk (top 20%) of type 2 diabetes.

Considering individuals’ GRS and lifestyle score together showed an increasing risk of developing type 2 diabetes from the low GRS/favorable-lifestyle category (HR, 1.0; reference) upward to the high GRS/unfavorable lifestyle (HR, 2.22; 95% CI, 1.76-2.81).

The Diet, Cancer, and Health cohort is supported by the Danish Cancer Society. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation. Ms. Jakupovic and associates are funded either directly or indirectly by the Novo Nordisk Foundation.

SOURCE: Jakupovic H et al. EASD 2019, Abstract 376.

BARCELONA – Obesity, more so than having a poor lifestyle, significantly raised the odds of developing type 2 diabetes, independent of individuals’ genetic susceptibility, according to data from a Danish population-based, case-cohort study.

In fact, having a body mass index (BMI) of more than 30 kg/m2 was linked with a 480% risk of incident type 2 diabetes, compared with being of normal weight (BMI, 18.5-24.9 kg/m2). The 95% confidence interval was 5.16-6.55. Being overweight (BMI, 25-29.9 kg/m2) also carried a 100% increased risk of type 2 diabetes (hazard ratio, 2.37; 95% CI, 2.15-2.62).

Having an unfavorable lifestyle – which was defined as having no or only one of several healthy-living characteristics, from not smoking and moderating alcohol use to eating a well-balanced, nutritious diet and exercising regularly – increased the risk of diabetes by 18%, compared with having a favorable lifestyle (HR, 1.18; 95% CI, 1.06-1.30).

Individuals with a high genetic risk score (GRS) had a 100% increased risk of developing the disease versus those with a low GRS (HR, 2.0; 95% CI, 1.1-1.3).

“High genetic risk, obesity, and [an] unfavorable lifestyle increase the individual-level risk of incident type 2 diabetes,” Hermina Jakupovic and associates reported in a poster presentation at the annual meeting of the European Association for the Study of Diabetes. Their results suggest that “the effect of obesity on type 2 diabetes risk is dominant over other risk factors, highlighting the importance of weight management in type 2 diabetes prevention.”

Ms. Jakupovic, a PhD student at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, and coauthors examined data on 9,555 participants of the Diet, Cancer, and Health cohort, a large, prospective study that has been running since the early 1990s.

Around half of the study sample were women and the mean age was 52 years. Just over one-fifth (22.8%) were obese, 43% were overweight, and the remaining 35.2% were of normal weight. A quarter (25.4%) had an unfavorable lifestyle, 40% a favorable lifestyle, and the remainder an “intermediate” lifestyle. Over a follow-up of almost 15 years, nearly half (49.5%) developed type 2 diabetes.

Genetic risk was assessed by a GRS comprising 193 genetic variants known to be strongly associated with type 2 diabetes, Ms. Jakupovic explained, adding that, using the GRS, patients were categorized into being at low (the lowest 20%), intermediate (middle 60%) and high risk (top 20%) of type 2 diabetes.

Considering individuals’ GRS and lifestyle score together showed an increasing risk of developing type 2 diabetes from the low GRS/favorable-lifestyle category (HR, 1.0; reference) upward to the high GRS/unfavorable lifestyle (HR, 2.22; 95% CI, 1.76-2.81).

The Diet, Cancer, and Health cohort is supported by the Danish Cancer Society. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation. Ms. Jakupovic and associates are funded either directly or indirectly by the Novo Nordisk Foundation.

SOURCE: Jakupovic H et al. EASD 2019, Abstract 376.

BARCELONA – Obesity, more so than having a poor lifestyle, significantly raised the odds of developing type 2 diabetes, independent of individuals’ genetic susceptibility, according to data from a Danish population-based, case-cohort study.

In fact, having a body mass index (BMI) of more than 30 kg/m2 was linked with a 480% risk of incident type 2 diabetes, compared with being of normal weight (BMI, 18.5-24.9 kg/m2). The 95% confidence interval was 5.16-6.55. Being overweight (BMI, 25-29.9 kg/m2) also carried a 100% increased risk of type 2 diabetes (hazard ratio, 2.37; 95% CI, 2.15-2.62).

Having an unfavorable lifestyle – which was defined as having no or only one of several healthy-living characteristics, from not smoking and moderating alcohol use to eating a well-balanced, nutritious diet and exercising regularly – increased the risk of diabetes by 18%, compared with having a favorable lifestyle (HR, 1.18; 95% CI, 1.06-1.30).

Individuals with a high genetic risk score (GRS) had a 100% increased risk of developing the disease versus those with a low GRS (HR, 2.0; 95% CI, 1.1-1.3).

“High genetic risk, obesity, and [an] unfavorable lifestyle increase the individual-level risk of incident type 2 diabetes,” Hermina Jakupovic and associates reported in a poster presentation at the annual meeting of the European Association for the Study of Diabetes. Their results suggest that “the effect of obesity on type 2 diabetes risk is dominant over other risk factors, highlighting the importance of weight management in type 2 diabetes prevention.”

Ms. Jakupovic, a PhD student at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, and coauthors examined data on 9,555 participants of the Diet, Cancer, and Health cohort, a large, prospective study that has been running since the early 1990s.

Around half of the study sample were women and the mean age was 52 years. Just over one-fifth (22.8%) were obese, 43% were overweight, and the remaining 35.2% were of normal weight. A quarter (25.4%) had an unfavorable lifestyle, 40% a favorable lifestyle, and the remainder an “intermediate” lifestyle. Over a follow-up of almost 15 years, nearly half (49.5%) developed type 2 diabetes.

Genetic risk was assessed by a GRS comprising 193 genetic variants known to be strongly associated with type 2 diabetes, Ms. Jakupovic explained, adding that, using the GRS, patients were categorized into being at low (the lowest 20%), intermediate (middle 60%) and high risk (top 20%) of type 2 diabetes.

Considering individuals’ GRS and lifestyle score together showed an increasing risk of developing type 2 diabetes from the low GRS/favorable-lifestyle category (HR, 1.0; reference) upward to the high GRS/unfavorable lifestyle (HR, 2.22; 95% CI, 1.76-2.81).

The Diet, Cancer, and Health cohort is supported by the Danish Cancer Society. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation. Ms. Jakupovic and associates are funded either directly or indirectly by the Novo Nordisk Foundation.

SOURCE: Jakupovic H et al. EASD 2019, Abstract 376.

Patients with type 1 diabetes who used a closed-loop insulin delivery system spent a greater percentage of time in their target blood glucose range, compared with patients using a sensor-augmented insulin pump.

The significant, between-group, mean-adjusted difference of 11 percentage points between the two groups translated into the closed-loop patients spending an additional 2.6 hr/day in the target range of 70-180 mg/dL, Susan A. Brown, MD, and colleagues wrote in the New England Journal of Medicine.

Most of the benefit occurred in the early morning hours, at 5 am, when 89% of patients using the closed-loop system remained in the target range, compared with 62% of those using the pump system, said Dr. Brown of the University of Virginia, Charlottesville, and colleagues.

The randomized study comprised 168 patients with a mean age of 33 years, although the age range was wide (14-71 years). The patients had a mean disease duration of 16 years. Their baseline glycated hemoglobin level ranged between 5.4% and 10.6%. At enrollment, 79% of patients used insulin pumps, and 21% used multiple daily insulin injections; 70% were using continuous glucose monitoring, of whom 86% were using pumps. Patients in both groups had follow-up visits at 2, 6, 13, and 26 weeks.

There were no dropouts in this study – 100% of clinical and telephone follow-ups were completed.

During the 6-month trial, the mean percentage of time spent in the glucose target range rose from 61% at baseline to 71% in the closed-loop group, but remained unchanged at 59% in the pump group. The difference became apparent very early in the study and remained consistent over its course.

“The mean percentage of time that the glucose level was in the target range was 70% in the closed-loop group and 59% in the control [pump] group during the daytime (6 a.m. to midnight) and 76% and 59%, respectively, during the nighttime (midnight to 6 am) ... and the greatest differences in the mean glucose level occurred at 5 a.m. and 6 a.m. [139 mg/dL in the closed-loop group vs. 166 mg/dL in the control group at both time points]. This diurnal pattern is a result of the increased aggressiveness of the algorithm to meet a lower glucose target during the second half of the night,” the authors noted.

The closed-loop system was also better than the pump system on all secondary endpoints, including the following:
 

• Glycated hemoglobin at 26 weeks: mean difference, –0.33 percentage points.
• Percentage of time with glucose higher than 180 mg/dL: mean difference, –10 percentage points (a difference of 2.4 hr/day).
• Percentage of time with glucose less than 70 mg/dL: mean difference, –0.88 percentage points (a difference of 13 min/day).

The other secondary endpoints – mean glucose level and mean glycated hemoglobin level – were also significantly better in those using the closed-loop system.

The benefits “consistently favored the closed-loop system across a broad range of baseline characteristics, including age, sex, body mass index, income, educational level, insulin pump or infection use, previous use of continuous glucose monitor, and glycated hemoglobin,” the authors said.

There were 17 adverse events in 16 patients in the closed-loop group, and 2 events in 2 patients in the pump group, but no incidents of severe hypoglycemia. One person in the closed-loop system experienced ketoacidosis because of a failure in the pump infusion set. There were 13 hyperglycemic or ketosis episodes in 12 patients in the closed-loop group, and 2 in 2 patients the pump group, but none of them met the criteria for diabetic ketoacidosis. All of these episodes were deemed related to infusion set failures.

There were three serious adverse events in the closed-loop group, and none related to the device. Blood ketones exceeding 1 mmol/L occurred in 11 closed-loop patients and 8 pump patients.

The results should be interpreted with consideration of potential group bias, the authors noted. “In our trial, 70% of the patients were using a continuous glucose monitor, and 79% were using an insulin pump at the time of enrollment, percentages that are substantially higher than the reported usage in the general population of type 1 diabetes. These data may reflect an interest in and willingness to use a closed-loop system among patients who were already using devices as part of diabetes management.”

Dr. Brown reported receiving grant support from Tandem Diabetes Care, Dexcom, and Roche Diagnostics. Other authors reported a range of support from numerous pharmaceutical and medical technology companies. Several reported patents on diabetes-related devices.

SOURCE: Brown SA et al. New Engl J Med. 2019 Oct 16. doi: 10.1056/NEJMoa1907863.

Patients with type 1 diabetes who used a closed-loop insulin delivery system spent a greater percentage of time in their target blood glucose range, compared with patients using a sensor-augmented insulin pump.

The significant, between-group, mean-adjusted difference of 11 percentage points between the two groups translated into the closed-loop patients spending an additional 2.6 hr/day in the target range of 70-180 mg/dL, Susan A. Brown, MD, and colleagues wrote in the New England Journal of Medicine.

Most of the benefit occurred in the early morning hours, at 5 am, when 89% of patients using the closed-loop system remained in the target range, compared with 62% of those using the pump system, said Dr. Brown of the University of Virginia, Charlottesville, and colleagues.

The randomized study comprised 168 patients with a mean age of 33 years, although the age range was wide (14-71 years). The patients had a mean disease duration of 16 years. Their baseline glycated hemoglobin level ranged between 5.4% and 10.6%. At enrollment, 79% of patients used insulin pumps, and 21% used multiple daily insulin injections; 70% were using continuous glucose monitoring, of whom 86% were using pumps. Patients in both groups had follow-up visits at 2, 6, 13, and 26 weeks.

There were no dropouts in this study – 100% of clinical and telephone follow-ups were completed.

During the 6-month trial, the mean percentage of time spent in the glucose target range rose from 61% at baseline to 71% in the closed-loop group, but remained unchanged at 59% in the pump group. The difference became apparent very early in the study and remained consistent over its course.

“The mean percentage of time that the glucose level was in the target range was 70% in the closed-loop group and 59% in the control [pump] group during the daytime (6 a.m. to midnight) and 76% and 59%, respectively, during the nighttime (midnight to 6 am) ... and the greatest differences in the mean glucose level occurred at 5 a.m. and 6 a.m. [139 mg/dL in the closed-loop group vs. 166 mg/dL in the control group at both time points]. This diurnal pattern is a result of the increased aggressiveness of the algorithm to meet a lower glucose target during the second half of the night,” the authors noted.

The closed-loop system was also better than the pump system on all secondary endpoints, including the following:
 

• Glycated hemoglobin at 26 weeks: mean difference, –0.33 percentage points.
• Percentage of time with glucose higher than 180 mg/dL: mean difference, –10 percentage points (a difference of 2.4 hr/day).
• Percentage of time with glucose less than 70 mg/dL: mean difference, –0.88 percentage points (a difference of 13 min/day).

The other secondary endpoints – mean glucose level and mean glycated hemoglobin level – were also significantly better in those using the closed-loop system.

The benefits “consistently favored the closed-loop system across a broad range of baseline characteristics, including age, sex, body mass index, income, educational level, insulin pump or infection use, previous use of continuous glucose monitor, and glycated hemoglobin,” the authors said.

There were 17 adverse events in 16 patients in the closed-loop group, and 2 events in 2 patients in the pump group, but no incidents of severe hypoglycemia. One person in the closed-loop system experienced ketoacidosis because of a failure in the pump infusion set. There were 13 hyperglycemic or ketosis episodes in 12 patients in the closed-loop group, and 2 in 2 patients the pump group, but none of them met the criteria for diabetic ketoacidosis. All of these episodes were deemed related to infusion set failures.

There were three serious adverse events in the closed-loop group, and none related to the device. Blood ketones exceeding 1 mmol/L occurred in 11 closed-loop patients and 8 pump patients.

The results should be interpreted with consideration of potential group bias, the authors noted. “In our trial, 70% of the patients were using a continuous glucose monitor, and 79% were using an insulin pump at the time of enrollment, percentages that are substantially higher than the reported usage in the general population of type 1 diabetes. These data may reflect an interest in and willingness to use a closed-loop system among patients who were already using devices as part of diabetes management.”

Dr. Brown reported receiving grant support from Tandem Diabetes Care, Dexcom, and Roche Diagnostics. Other authors reported a range of support from numerous pharmaceutical and medical technology companies. Several reported patents on diabetes-related devices.

SOURCE: Brown SA et al. New Engl J Med. 2019 Oct 16. doi: 10.1056/NEJMoa1907863.

Patients with type 1 diabetes who used a closed-loop insulin delivery system spent a greater percentage of time in their target blood glucose range, compared with patients using a sensor-augmented insulin pump.

The significant, between-group, mean-adjusted difference of 11 percentage points between the two groups translated into the closed-loop patients spending an additional 2.6 hr/day in the target range of 70-180 mg/dL, Susan A. Brown, MD, and colleagues wrote in the New England Journal of Medicine.

Most of the benefit occurred in the early morning hours, at 5 am, when 89% of patients using the closed-loop system remained in the target range, compared with 62% of those using the pump system, said Dr. Brown of the University of Virginia, Charlottesville, and colleagues.

The randomized study comprised 168 patients with a mean age of 33 years, although the age range was wide (14-71 years). The patients had a mean disease duration of 16 years. Their baseline glycated hemoglobin level ranged between 5.4% and 10.6%. At enrollment, 79% of patients used insulin pumps, and 21% used multiple daily insulin injections; 70% were using continuous glucose monitoring, of whom 86% were using pumps. Patients in both groups had follow-up visits at 2, 6, 13, and 26 weeks.

There were no dropouts in this study – 100% of clinical and telephone follow-ups were completed.

During the 6-month trial, the mean percentage of time spent in the glucose target range rose from 61% at baseline to 71% in the closed-loop group, but remained unchanged at 59% in the pump group. The difference became apparent very early in the study and remained consistent over its course.

“The mean percentage of time that the glucose level was in the target range was 70% in the closed-loop group and 59% in the control [pump] group during the daytime (6 a.m. to midnight) and 76% and 59%, respectively, during the nighttime (midnight to 6 am) ... and the greatest differences in the mean glucose level occurred at 5 a.m. and 6 a.m. [139 mg/dL in the closed-loop group vs. 166 mg/dL in the control group at both time points]. This diurnal pattern is a result of the increased aggressiveness of the algorithm to meet a lower glucose target during the second half of the night,” the authors noted.

The closed-loop system was also better than the pump system on all secondary endpoints, including the following:
 

• Glycated hemoglobin at 26 weeks: mean difference, –0.33 percentage points.
• Percentage of time with glucose higher than 180 mg/dL: mean difference, –10 percentage points (a difference of 2.4 hr/day).
• Percentage of time with glucose less than 70 mg/dL: mean difference, –0.88 percentage points (a difference of 13 min/day).

The other secondary endpoints – mean glucose level and mean glycated hemoglobin level – were also significantly better in those using the closed-loop system.

The benefits “consistently favored the closed-loop system across a broad range of baseline characteristics, including age, sex, body mass index, income, educational level, insulin pump or infection use, previous use of continuous glucose monitor, and glycated hemoglobin,” the authors said.

There were 17 adverse events in 16 patients in the closed-loop group, and 2 events in 2 patients in the pump group, but no incidents of severe hypoglycemia. One person in the closed-loop system experienced ketoacidosis because of a failure in the pump infusion set. There were 13 hyperglycemic or ketosis episodes in 12 patients in the closed-loop group, and 2 in 2 patients the pump group, but none of them met the criteria for diabetic ketoacidosis. All of these episodes were deemed related to infusion set failures.

There were three serious adverse events in the closed-loop group, and none related to the device. Blood ketones exceeding 1 mmol/L occurred in 11 closed-loop patients and 8 pump patients.

The results should be interpreted with consideration of potential group bias, the authors noted. “In our trial, 70% of the patients were using a continuous glucose monitor, and 79% were using an insulin pump at the time of enrollment, percentages that are substantially higher than the reported usage in the general population of type 1 diabetes. These data may reflect an interest in and willingness to use a closed-loop system among patients who were already using devices as part of diabetes management.”

Dr. Brown reported receiving grant support from Tandem Diabetes Care, Dexcom, and Roche Diagnostics. Other authors reported a range of support from numerous pharmaceutical and medical technology companies. Several reported patents on diabetes-related devices.

SOURCE: Brown SA et al. New Engl J Med. 2019 Oct 16. doi: 10.1056/NEJMoa1907863.

The US is in the midst of a chronic disease crisis. According to the latest published data available, 60% of Americans have at least 1 chronic condition, and 42% have ≥ 2 chronic conditions.¹ Estimates by the Health Resources and Services Administration (HRSA) indicate a current shortfall of 13 800 primary care physicians and a projected escalation of that shortage to be between 14 800 and 49 300 physicians by the year 2030.²

The US Public Health Service (USPHS) has used pharmacists since 1930 to provide direct patient care to underserved and vulnerable populations. Clinical pharmacists currently serve in direct patient care roles within the Indian Health Service (IHS), Federal Bureau of Prisons (BOP), Immigration and Customs Enforcement (ICE), and the United States Coast Guard (USCG) in many states (Figure). These pharmacists play a vital role in improving access to care and delivering quality care by managing acute and chronic diseases in collaborative practice settings and pharmacist-managed clinics.

It has previously been reported that in the face of physician shortages and growing demand for primary health care providers, pharmacists are well-equipped and motivated to meet this demand.³ A review of the previous 2 years of outcomes reported by clinical pharmacists certified through the USPHS National Clinical Pharmacy Specialist (NCPS) Committee are presented to demonstrate the impact of pharmacists in advancing the health of the populations they serve and to showcase a model for ameliorating the ongoing physician shortage.

Background

The USPHS NCPS Committee serves to promote uniform competency among clinical pharmacists by establishing national standards for protocols, collaborative practice agreements (CPAs), credentialing and privileging of pharmacists, and by collecting, reviewing, and publishing health care outcomes. The committee, whose constituents include pharmacist and physician subject matter experts from across USPHS agencies, reviews applications and protocols and certifies pharmacists (civilian and uniformed) to recognize an advanced scope of practice in managing various diseases and optimizing medication therapy. NCPScertified pharmacists manage a wide spectrum of diseases, including coagulopathy, asthma, diabetes mellitus (DM), hepatitis C, HIV, hypertension, pain, seizure disorders, and tobacco use disorders.

Clinical pharmacists practicing chronic disease management establish a clinical service in collaboration with 1 or more physicians, physician assistants, or nurse practitioners. In this collaborative practice, the health care practitioner(s) refer patients to be managed by a pharmacist for specific medical needs, such as anticoagulation management, or for holistic medication- focused care (eg, cardiovascular risk reduction, DM management, HIV, hepatitis, or mental health). The pharmacist may order and interpret laboratory tests, check vital signs, perform a limited physical examination, and gather other pertinent information from the patient and the medical record in order to provide the best possible care to the patient.

Medications may be started, stopped, or adjusted, education is provided, and therapeutic lifestyle interventions may be recommended. The pharmacist-run clinic provides the patient more frequent interaction with a health care professional (pharmacist) and focused disease management. As a result, pharmacists increase access to care and allow the medical team to handle a larger panel of patients as the practitioner delegates specified diseases to the pharmacist- managed clinic(s). The number of NCPS-certified pharmacists grew 46% from 2012 (n = 230) to 2017 (n = 336), reflecting an evolution of pharmacists’ practice to better meet the need of patients across the nation.

Methods

The NCPS Committee requires NCPS pharmacists to report data annually from all patients referred for pharmacist management for specific diseases in which they have been certified. The data reflect the patient’s clinical outcome goal status at the time of referral as well as the same status at the end of the reporting period or on release from the pharmacist-run clinic. These data describe the impact prescribing pharmacists have on patients reaching clinical outcome goals acting as the team member specializing in the medication selection and dosing aspect of care.

These records were reviewed for the fiscal year (FY) periods of October 1, 2015 to September 30, 2016 (FY 2016) and October 1, 2016 to September 30, 2017 (FY 2017). A systematic review of submitted reports resulted in 181 reports that included all requested data points for the disease as published here for FYs 2016 and 2017. These include 66 reports from FY 2016 and 115 reports from FY 2017; they cover 76 BOP and IHS facilities located across 24 states. Table 1 shows the number of outcome reports collected from 104 075 patient visits in pharmacist-run clinics in FYs 2016 and 2017.

Results

The following tables represent the standardized outcomes collected by NCPS-certified pharmacists providing direct patient care. Patients on anticoagulants (eg, warfarin) require special monitoring and education for drug interactions and adverse effects. NCPS-certified pharmacists were able to achieve a mean patient time in therapeutic range (TTR) of 67.6% (regardless of indication) over the 2 years (calculated per each facility by Rosendaal method of linear interpolation then combined in a weighted average per visit). The TTR produced by NCPS-certified pharmacists are consistent with Chest Guidelines and Expert Panel Report suggesting that TTR should be between 65% and 70%.⁴ Table 2 shows data from 100 reports with 68 255 patient visits for anticoagulation management.

DM management can be complex and time-intensive. NCPS data indicate pharmacist intervention resulted in a mean decrease in hemoglobin A_1c (HbA1c) of 1.8% from a baseline of 10.2% (decrease calculated per each facility then combined by weighted average per visit). Table 3 shows data from 30 reports with 16 518 patient visits for DM care.

In addition to diet and exercise, medication management plays a vital role in managing hypertension. Patients managed by an NCPS-certified pharmacist experienced a mean decrease in blood pressure from 144/83 to 133/77, putting them in goal for both systolic and diastolic ranges (decrease calculated per each facility then combined by weighted average per visit). Table 4 shows data from 16 reports and 7997 patient visits for treatment of hypertension.

HIV viral suppression is vital in order to best manage patients with HIV and reduce the risk of transmission. Pharmacistled clinics have shown a 32.9% absolute improvement in patients at goal (viral load < 50 copies/mL), from a mean baseline of 46.0% to a mean final assessment of 71.6% of patients at goal (combined by weighted average visits). Table 5 shows data from 6 reports covering 1532 patient encounters for management of HIV.

Nicotine dependence includes the use of cigarettes, cigars, pipe tobacco, chewing tobacco, and vaping products containing nicotine. NCPS-certified pharmacists have successfully helped patients improve their chance of quitting, with a 6-month quit rate of 22.2% (quit rate calculated per each facility then combined by weighted average by visits), which is higher than the national average of 9.4% as reported by the Centers for Disease and Control and Prevention. ⁵ Table 6 shows 29 reports covering 9773 patient visits for treatment of nicotine dependence.

Discussion

These data demonstrate the ability of advanced practice pharmacists in multiple locations within the federal sector to improve targeted clinical outcomes in patients with varying diseases. These results are strengthened by their varied origins as well as the improvements observed across the board. Limitations include the general lack of a comparable dataset, manual method of selfreporting by the individual facilities, and the relatively limited array of diseases reported. Although NCPS-certified pharmacists are currently providing care for patients with hepatitis C, asthma, seizure, pain and other diseases not reported here, there are insufficient data collected for FYs 2016 and 2017 to merit inclusion within this report.

Pharmacists are trusted, readily available medication experts. In a clinical role, NCPS-certified pharmacists have increased access to primary care services and demonstrated beneficial impact on important health outcomes as exhibited by the data reported above. Clinical pharmacy is a growing field, and NCPS has displayed continual growth in both the number of NCPS-certified pharmacists and the number of patient encounters performed by these providers. As more pharmacists in all settings collaborate with medical providers to offer high-quality clinical care, these providers will have more opportunity to delegate disease management. Continued reporting of clinical pharmacy outcomes is expected to increase confidence in pharmacists as primary care providers, increase utilization of pharmacy clinical services, and assist in easing the burden of primary care provider shortages across our nation.

Although these outcomes indicate demonstrable benefit in patient-centered outcomes, the need for ongoing assessment and continued improvement is not obviated. Future efforts may benefit from a comparison of alternative approaches to better facilitate the establishment of best practices. Alignment of clinical outcomes with the Centers for Medicare and Medicaid Services (CMS) Electronic Clinical Quality Measures, where applicable, also may prove beneficial by automating the reporting process and thereby decreasing the burden of reporting as well as providing an avenue for standard comparison across multiple populations. Clinical pharmacy interventions have positive outcomes based on the NCPS model, and the NCPS Committee invites other clinical settings to report outcomes data with which to compare.

Conclusion

The NCPS Committee has documented positive outcomes of clinical pharmacy intervention and anticipates growth of the pharmacy profession as additional states and health systems recognize the capacity of the pharmacist to provide high-quality, multidisciplinary patient care. Clinical pharmacists are prepared to address critical health care needs as the US continues to face a PCP shortage.² The NCPS Committee challenges those participating in clinical pharmacy practice to report outcomes to amplify this body of evidence.

Acknowledgments
NCPS-certified pharmacists provided the outcomes detailed in this report. For document review and edits: Federal Bureau of Prison Publication Review Workgroup; RADM Ty Bingham, USPHS; CAPT Cindy Gunderson, USPHS; CAPT Kevin Brooks, USPHS.

The US is in the midst of a chronic disease crisis. According to the latest published data available, 60% of Americans have at least 1 chronic condition, and 42% have ≥ 2 chronic conditions.¹ Estimates by the Health Resources and Services Administration (HRSA) indicate a current shortfall of 13 800 primary care physicians and a projected escalation of that shortage to be between 14 800 and 49 300 physicians by the year 2030.²

The US Public Health Service (USPHS) has used pharmacists since 1930 to provide direct patient care to underserved and vulnerable populations. Clinical pharmacists currently serve in direct patient care roles within the Indian Health Service (IHS), Federal Bureau of Prisons (BOP), Immigration and Customs Enforcement (ICE), and the United States Coast Guard (USCG) in many states (Figure). These pharmacists play a vital role in improving access to care and delivering quality care by managing acute and chronic diseases in collaborative practice settings and pharmacist-managed clinics.

It has previously been reported that in the face of physician shortages and growing demand for primary health care providers, pharmacists are well-equipped and motivated to meet this demand.³ A review of the previous 2 years of outcomes reported by clinical pharmacists certified through the USPHS National Clinical Pharmacy Specialist (NCPS) Committee are presented to demonstrate the impact of pharmacists in advancing the health of the populations they serve and to showcase a model for ameliorating the ongoing physician shortage.

Background

The USPHS NCPS Committee serves to promote uniform competency among clinical pharmacists by establishing national standards for protocols, collaborative practice agreements (CPAs), credentialing and privileging of pharmacists, and by collecting, reviewing, and publishing health care outcomes. The committee, whose constituents include pharmacist and physician subject matter experts from across USPHS agencies, reviews applications and protocols and certifies pharmacists (civilian and uniformed) to recognize an advanced scope of practice in managing various diseases and optimizing medication therapy. NCPScertified pharmacists manage a wide spectrum of diseases, including coagulopathy, asthma, diabetes mellitus (DM), hepatitis C, HIV, hypertension, pain, seizure disorders, and tobacco use disorders.

Clinical pharmacists practicing chronic disease management establish a clinical service in collaboration with 1 or more physicians, physician assistants, or nurse practitioners. In this collaborative practice, the health care practitioner(s) refer patients to be managed by a pharmacist for specific medical needs, such as anticoagulation management, or for holistic medication- focused care (eg, cardiovascular risk reduction, DM management, HIV, hepatitis, or mental health). The pharmacist may order and interpret laboratory tests, check vital signs, perform a limited physical examination, and gather other pertinent information from the patient and the medical record in order to provide the best possible care to the patient.

Medications may be started, stopped, or adjusted, education is provided, and therapeutic lifestyle interventions may be recommended. The pharmacist-run clinic provides the patient more frequent interaction with a health care professional (pharmacist) and focused disease management. As a result, pharmacists increase access to care and allow the medical team to handle a larger panel of patients as the practitioner delegates specified diseases to the pharmacist- managed clinic(s). The number of NCPS-certified pharmacists grew 46% from 2012 (n = 230) to 2017 (n = 336), reflecting an evolution of pharmacists’ practice to better meet the need of patients across the nation.

Methods

The NCPS Committee requires NCPS pharmacists to report data annually from all patients referred for pharmacist management for specific diseases in which they have been certified. The data reflect the patient’s clinical outcome goal status at the time of referral as well as the same status at the end of the reporting period or on release from the pharmacist-run clinic. These data describe the impact prescribing pharmacists have on patients reaching clinical outcome goals acting as the team member specializing in the medication selection and dosing aspect of care.

These records were reviewed for the fiscal year (FY) periods of October 1, 2015 to September 30, 2016 (FY 2016) and October 1, 2016 to September 30, 2017 (FY 2017). A systematic review of submitted reports resulted in 181 reports that included all requested data points for the disease as published here for FYs 2016 and 2017. These include 66 reports from FY 2016 and 115 reports from FY 2017; they cover 76 BOP and IHS facilities located across 24 states. Table 1 shows the number of outcome reports collected from 104 075 patient visits in pharmacist-run clinics in FYs 2016 and 2017.

Results

The following tables represent the standardized outcomes collected by NCPS-certified pharmacists providing direct patient care. Patients on anticoagulants (eg, warfarin) require special monitoring and education for drug interactions and adverse effects. NCPS-certified pharmacists were able to achieve a mean patient time in therapeutic range (TTR) of 67.6% (regardless of indication) over the 2 years (calculated per each facility by Rosendaal method of linear interpolation then combined in a weighted average per visit). The TTR produced by NCPS-certified pharmacists are consistent with Chest Guidelines and Expert Panel Report suggesting that TTR should be between 65% and 70%.⁴ Table 2 shows data from 100 reports with 68 255 patient visits for anticoagulation management.

DM management can be complex and time-intensive. NCPS data indicate pharmacist intervention resulted in a mean decrease in hemoglobin A_1c (HbA1c) of 1.8% from a baseline of 10.2% (decrease calculated per each facility then combined by weighted average per visit). Table 3 shows data from 30 reports with 16 518 patient visits for DM care.

In addition to diet and exercise, medication management plays a vital role in managing hypertension. Patients managed by an NCPS-certified pharmacist experienced a mean decrease in blood pressure from 144/83 to 133/77, putting them in goal for both systolic and diastolic ranges (decrease calculated per each facility then combined by weighted average per visit). Table 4 shows data from 16 reports and 7997 patient visits for treatment of hypertension.

HIV viral suppression is vital in order to best manage patients with HIV and reduce the risk of transmission. Pharmacistled clinics have shown a 32.9% absolute improvement in patients at goal (viral load < 50 copies/mL), from a mean baseline of 46.0% to a mean final assessment of 71.6% of patients at goal (combined by weighted average visits). Table 5 shows data from 6 reports covering 1532 patient encounters for management of HIV.

Nicotine dependence includes the use of cigarettes, cigars, pipe tobacco, chewing tobacco, and vaping products containing nicotine. NCPS-certified pharmacists have successfully helped patients improve their chance of quitting, with a 6-month quit rate of 22.2% (quit rate calculated per each facility then combined by weighted average by visits), which is higher than the national average of 9.4% as reported by the Centers for Disease and Control and Prevention. ⁵ Table 6 shows 29 reports covering 9773 patient visits for treatment of nicotine dependence.

Discussion

These data demonstrate the ability of advanced practice pharmacists in multiple locations within the federal sector to improve targeted clinical outcomes in patients with varying diseases. These results are strengthened by their varied origins as well as the improvements observed across the board. Limitations include the general lack of a comparable dataset, manual method of selfreporting by the individual facilities, and the relatively limited array of diseases reported. Although NCPS-certified pharmacists are currently providing care for patients with hepatitis C, asthma, seizure, pain and other diseases not reported here, there are insufficient data collected for FYs 2016 and 2017 to merit inclusion within this report.

Pharmacists are trusted, readily available medication experts. In a clinical role, NCPS-certified pharmacists have increased access to primary care services and demonstrated beneficial impact on important health outcomes as exhibited by the data reported above. Clinical pharmacy is a growing field, and NCPS has displayed continual growth in both the number of NCPS-certified pharmacists and the number of patient encounters performed by these providers. As more pharmacists in all settings collaborate with medical providers to offer high-quality clinical care, these providers will have more opportunity to delegate disease management. Continued reporting of clinical pharmacy outcomes is expected to increase confidence in pharmacists as primary care providers, increase utilization of pharmacy clinical services, and assist in easing the burden of primary care provider shortages across our nation.

Although these outcomes indicate demonstrable benefit in patient-centered outcomes, the need for ongoing assessment and continued improvement is not obviated. Future efforts may benefit from a comparison of alternative approaches to better facilitate the establishment of best practices. Alignment of clinical outcomes with the Centers for Medicare and Medicaid Services (CMS) Electronic Clinical Quality Measures, where applicable, also may prove beneficial by automating the reporting process and thereby decreasing the burden of reporting as well as providing an avenue for standard comparison across multiple populations. Clinical pharmacy interventions have positive outcomes based on the NCPS model, and the NCPS Committee invites other clinical settings to report outcomes data with which to compare.

Conclusion

The NCPS Committee has documented positive outcomes of clinical pharmacy intervention and anticipates growth of the pharmacy profession as additional states and health systems recognize the capacity of the pharmacist to provide high-quality, multidisciplinary patient care. Clinical pharmacists are prepared to address critical health care needs as the US continues to face a PCP shortage.² The NCPS Committee challenges those participating in clinical pharmacy practice to report outcomes to amplify this body of evidence.

Acknowledgments
NCPS-certified pharmacists provided the outcomes detailed in this report. For document review and edits: Federal Bureau of Prison Publication Review Workgroup; RADM Ty Bingham, USPHS; CAPT Cindy Gunderson, USPHS; CAPT Kevin Brooks, USPHS.

The US is in the midst of a chronic disease crisis. According to the latest published data available, 60% of Americans have at least 1 chronic condition, and 42% have ≥ 2 chronic conditions.¹ Estimates by the Health Resources and Services Administration (HRSA) indicate a current shortfall of 13 800 primary care physicians and a projected escalation of that shortage to be between 14 800 and 49 300 physicians by the year 2030.²

The US Public Health Service (USPHS) has used pharmacists since 1930 to provide direct patient care to underserved and vulnerable populations. Clinical pharmacists currently serve in direct patient care roles within the Indian Health Service (IHS), Federal Bureau of Prisons (BOP), Immigration and Customs Enforcement (ICE), and the United States Coast Guard (USCG) in many states (Figure). These pharmacists play a vital role in improving access to care and delivering quality care by managing acute and chronic diseases in collaborative practice settings and pharmacist-managed clinics.

It has previously been reported that in the face of physician shortages and growing demand for primary health care providers, pharmacists are well-equipped and motivated to meet this demand.³ A review of the previous 2 years of outcomes reported by clinical pharmacists certified through the USPHS National Clinical Pharmacy Specialist (NCPS) Committee are presented to demonstrate the impact of pharmacists in advancing the health of the populations they serve and to showcase a model for ameliorating the ongoing physician shortage.

Background

The USPHS NCPS Committee serves to promote uniform competency among clinical pharmacists by establishing national standards for protocols, collaborative practice agreements (CPAs), credentialing and privileging of pharmacists, and by collecting, reviewing, and publishing health care outcomes. The committee, whose constituents include pharmacist and physician subject matter experts from across USPHS agencies, reviews applications and protocols and certifies pharmacists (civilian and uniformed) to recognize an advanced scope of practice in managing various diseases and optimizing medication therapy. NCPScertified pharmacists manage a wide spectrum of diseases, including coagulopathy, asthma, diabetes mellitus (DM), hepatitis C, HIV, hypertension, pain, seizure disorders, and tobacco use disorders.

Clinical pharmacists practicing chronic disease management establish a clinical service in collaboration with 1 or more physicians, physician assistants, or nurse practitioners. In this collaborative practice, the health care practitioner(s) refer patients to be managed by a pharmacist for specific medical needs, such as anticoagulation management, or for holistic medication- focused care (eg, cardiovascular risk reduction, DM management, HIV, hepatitis, or mental health). The pharmacist may order and interpret laboratory tests, check vital signs, perform a limited physical examination, and gather other pertinent information from the patient and the medical record in order to provide the best possible care to the patient.

Medications may be started, stopped, or adjusted, education is provided, and therapeutic lifestyle interventions may be recommended. The pharmacist-run clinic provides the patient more frequent interaction with a health care professional (pharmacist) and focused disease management. As a result, pharmacists increase access to care and allow the medical team to handle a larger panel of patients as the practitioner delegates specified diseases to the pharmacist- managed clinic(s). The number of NCPS-certified pharmacists grew 46% from 2012 (n = 230) to 2017 (n = 336), reflecting an evolution of pharmacists’ practice to better meet the need of patients across the nation.

Methods

The NCPS Committee requires NCPS pharmacists to report data annually from all patients referred for pharmacist management for specific diseases in which they have been certified. The data reflect the patient’s clinical outcome goal status at the time of referral as well as the same status at the end of the reporting period or on release from the pharmacist-run clinic. These data describe the impact prescribing pharmacists have on patients reaching clinical outcome goals acting as the team member specializing in the medication selection and dosing aspect of care.

These records were reviewed for the fiscal year (FY) periods of October 1, 2015 to September 30, 2016 (FY 2016) and October 1, 2016 to September 30, 2017 (FY 2017). A systematic review of submitted reports resulted in 181 reports that included all requested data points for the disease as published here for FYs 2016 and 2017. These include 66 reports from FY 2016 and 115 reports from FY 2017; they cover 76 BOP and IHS facilities located across 24 states. Table 1 shows the number of outcome reports collected from 104 075 patient visits in pharmacist-run clinics in FYs 2016 and 2017.

Results

The following tables represent the standardized outcomes collected by NCPS-certified pharmacists providing direct patient care. Patients on anticoagulants (eg, warfarin) require special monitoring and education for drug interactions and adverse effects. NCPS-certified pharmacists were able to achieve a mean patient time in therapeutic range (TTR) of 67.6% (regardless of indication) over the 2 years (calculated per each facility by Rosendaal method of linear interpolation then combined in a weighted average per visit). The TTR produced by NCPS-certified pharmacists are consistent with Chest Guidelines and Expert Panel Report suggesting that TTR should be between 65% and 70%.⁴ Table 2 shows data from 100 reports with 68 255 patient visits for anticoagulation management.

DM management can be complex and time-intensive. NCPS data indicate pharmacist intervention resulted in a mean decrease in hemoglobin A_1c (HbA1c) of 1.8% from a baseline of 10.2% (decrease calculated per each facility then combined by weighted average per visit). Table 3 shows data from 30 reports with 16 518 patient visits for DM care.

In addition to diet and exercise, medication management plays a vital role in managing hypertension. Patients managed by an NCPS-certified pharmacist experienced a mean decrease in blood pressure from 144/83 to 133/77, putting them in goal for both systolic and diastolic ranges (decrease calculated per each facility then combined by weighted average per visit). Table 4 shows data from 16 reports and 7997 patient visits for treatment of hypertension.

HIV viral suppression is vital in order to best manage patients with HIV and reduce the risk of transmission. Pharmacistled clinics have shown a 32.9% absolute improvement in patients at goal (viral load < 50 copies/mL), from a mean baseline of 46.0% to a mean final assessment of 71.6% of patients at goal (combined by weighted average visits). Table 5 shows data from 6 reports covering 1532 patient encounters for management of HIV.

Nicotine dependence includes the use of cigarettes, cigars, pipe tobacco, chewing tobacco, and vaping products containing nicotine. NCPS-certified pharmacists have successfully helped patients improve their chance of quitting, with a 6-month quit rate of 22.2% (quit rate calculated per each facility then combined by weighted average by visits), which is higher than the national average of 9.4% as reported by the Centers for Disease and Control and Prevention. ⁵ Table 6 shows 29 reports covering 9773 patient visits for treatment of nicotine dependence.

Discussion

These data demonstrate the ability of advanced practice pharmacists in multiple locations within the federal sector to improve targeted clinical outcomes in patients with varying diseases. These results are strengthened by their varied origins as well as the improvements observed across the board. Limitations include the general lack of a comparable dataset, manual method of selfreporting by the individual facilities, and the relatively limited array of diseases reported. Although NCPS-certified pharmacists are currently providing care for patients with hepatitis C, asthma, seizure, pain and other diseases not reported here, there are insufficient data collected for FYs 2016 and 2017 to merit inclusion within this report.

Pharmacists are trusted, readily available medication experts. In a clinical role, NCPS-certified pharmacists have increased access to primary care services and demonstrated beneficial impact on important health outcomes as exhibited by the data reported above. Clinical pharmacy is a growing field, and NCPS has displayed continual growth in both the number of NCPS-certified pharmacists and the number of patient encounters performed by these providers. As more pharmacists in all settings collaborate with medical providers to offer high-quality clinical care, these providers will have more opportunity to delegate disease management. Continued reporting of clinical pharmacy outcomes is expected to increase confidence in pharmacists as primary care providers, increase utilization of pharmacy clinical services, and assist in easing the burden of primary care provider shortages across our nation.

Although these outcomes indicate demonstrable benefit in patient-centered outcomes, the need for ongoing assessment and continued improvement is not obviated. Future efforts may benefit from a comparison of alternative approaches to better facilitate the establishment of best practices. Alignment of clinical outcomes with the Centers for Medicare and Medicaid Services (CMS) Electronic Clinical Quality Measures, where applicable, also may prove beneficial by automating the reporting process and thereby decreasing the burden of reporting as well as providing an avenue for standard comparison across multiple populations. Clinical pharmacy interventions have positive outcomes based on the NCPS model, and the NCPS Committee invites other clinical settings to report outcomes data with which to compare.

Conclusion

The NCPS Committee has documented positive outcomes of clinical pharmacy intervention and anticipates growth of the pharmacy profession as additional states and health systems recognize the capacity of the pharmacist to provide high-quality, multidisciplinary patient care. Clinical pharmacists are prepared to address critical health care needs as the US continues to face a PCP shortage.² The NCPS Committee challenges those participating in clinical pharmacy practice to report outcomes to amplify this body of evidence.

Acknowledgments
NCPS-certified pharmacists provided the outcomes detailed in this report. For document review and edits: Federal Bureau of Prison Publication Review Workgroup; RADM Ty Bingham, USPHS; CAPT Cindy Gunderson, USPHS; CAPT Kevin Brooks, USPHS.

BARCELONA – The glucagon-like peptide-1 receptor agonist (GLP-1 RA) liraglutide added onto metformin with or without basal insulin effectively reduced hemoglobin A_1c and fasting plasma glucose levels in children with type 2 diabetes in the 52-week ELLIPSE study.

Sara Freeman/MDedge News

The primary endpoint of the trial, which was the mean change in HbA_1c from baseline to 26 weeks, was met, with a greater percentage point decrease with liraglutide (Victoza) than placebo (–0.64 vs. +0.42), with an estimated treatment difference of –1.06 percentage points (P less than .001). At the end of the study, the percentage point changes were –0.50 and +0.80, with a between-group difference of –1.30 in favor of liraglutide.

“Those of us working in pediatric practice are seeing an increasing demand for our clinical services in children with type 2 diabetes,” study investigator Timothy Barrett, PhD, MBBS, observed at the annual meeting of the European Association for the Study of Diabetes. This reflects the increasing prevalence of type 2 diabetes in this age group and is most likely linked to the rising rates of obesity and overweight that have been reported widely in young people in recent years, he added.

“Unfortunately, we look with envy upon our adult physician colleagues, and the range of treatments they have available to treat type 2 diabetes in adults.” In pediatrics, the only licensed treatments that have been available until recently were metformin and insulin, with the latter being an “illogical treatment to treat those with obesity-related diabetes.” The study’s findings, however, support liraglutide as another option to consider, said Dr. Barrett, a pediatric endocrinologist and professor of pediatrics and child health based at the University of Birmingham, England.

“Liraglutide at doses of up to 1.8 mg/day when added to metformin, and basal insulin if required, does seem to offer an additional treatment option for children and young people with type 2 diabetes who require improved glycemic control after they’ve reached a maximum dose of metformin,” he said.

ELLIPSE (Evaluation of Liraglutide in Pediatrics with Diabetes) was a multicenter, randomized, parallel group, placebo-controlled trial to assess the efficacy and safety of liraglutide as an add-on treatment to metformin, with or without basal insulin, in 134 overweight or obese children and adolescents (aged 10-17) with type 2 diabetes.

For inclusion, patients had to be able to complete the trial before their 18th birthday, and have an HbA_1c of at least 7% if being treated with diet and exercise, or 6.5% or higher if already being treated with metformin, with or without insulin. Body mass index had to be above the 85the percentile for their age and sex.

Of 307 children and adolescents screened at 84 centers in 25 countries, 135 were randomized and 134 were treated between 2012 and 2018. Screening took place over a period of 2 weeks, after which time those eligible for the trial underwent a 3- to 4-week period where their dose of metformin was titrated if needed followed by an 8-week maintenance period. Only after that was randomization to liraglutide or placebo done, with the GLP-1R started at a subcutaneous dose of 0.6 mg and titrated up to 1.2 or 1.8 mg over 3 days to achieve a fasting plasma glucose (FPG) of less than 6.1 mmol/L (110 mg/dL). However, not all patients were escalated to the top dose, Dr. Barrett noted.

The mean age of patients in the trial was 14.5 years; about 60% of patients were female. The duration of diabetes was about 1.9 years and the average body weight and BMI a respective 91 kg and 33 kg/m².

Over the course of the study, FPG fell by 1.06 mmol/L at week 26 and 1.03 mmol/L at week 52 in the liraglutide group but rose in the placebo group by 0.80 and 0.78 mmol/L, respectively. The estimated treatment difference was –1.88 (P = .002) and –1.81 at 26 an 52 weeks, respectively.

What was “a really gratifying to see,” said Dr. Barrett, was that the proportion of children and young people achieving a glycemic target of an HbA_1c of less than 7% by the end of the double-blind treatment period was significantly higher in the liraglutide than placebo group, at 63.7% and 36.5%, respectively.

Most of the adverse effects seen in the study were gastrointestinal symptoms, including nausea, vomiting, and diarrhea, in about 20% of liraglutide-treated patients, compared with roughly 10% of placebo-treated patients. “This is really reflected in the adult studies as well, and many of these were thankfully transient.”

As for hypoglycemia, Dr. Barrett reported that there was a higher rate in liraglutide- than placebo-treated patients (45.5% vs. 25% for any event), although there were no severe episodes in the liraglutide group and one in the placebo group. Almost a third (31%) of hypoglycemic episodes were asymptomatic, versus 17.6% for the placebo group.

“This is the first successfully completed phase 3 trial showing efficacy of a noninsulin agent, in this case, for children who do not get managed solely on metformin monotherapy,” Dr. Barrett said.

The Food and Drug Administration has approved liraglutide for use in pediatric patients 10 years or older with type 2 diabetes, based in part on results of the ELLIPSE results, Novo Nordisk announced in June. The trial results were published prior to the EASD meeting (Tamborlane WV et al. N Engl J Med. 2019 Aug 15;381:637-46).

Novo Nordisk initiated and funded the trial, and most of the investigators reported receiving funds from the company outside the submitted work. Dr Barrett disclosed being a consultant to and/or receiving honoraria from AstraZeneca, Novo Nordisk and Servier.

SOURCE: Barrett T et al. EASD 2019. Abstract 84.

BARCELONA – The glucagon-like peptide-1 receptor agonist (GLP-1 RA) liraglutide added onto metformin with or without basal insulin effectively reduced hemoglobin A_1c and fasting plasma glucose levels in children with type 2 diabetes in the 52-week ELLIPSE study.

Sara Freeman/MDedge News

The primary endpoint of the trial, which was the mean change in HbA_1c from baseline to 26 weeks, was met, with a greater percentage point decrease with liraglutide (Victoza) than placebo (–0.64 vs. +0.42), with an estimated treatment difference of –1.06 percentage points (P less than .001). At the end of the study, the percentage point changes were –0.50 and +0.80, with a between-group difference of –1.30 in favor of liraglutide.

“Those of us working in pediatric practice are seeing an increasing demand for our clinical services in children with type 2 diabetes,” study investigator Timothy Barrett, PhD, MBBS, observed at the annual meeting of the European Association for the Study of Diabetes. This reflects the increasing prevalence of type 2 diabetes in this age group and is most likely linked to the rising rates of obesity and overweight that have been reported widely in young people in recent years, he added.

“Unfortunately, we look with envy upon our adult physician colleagues, and the range of treatments they have available to treat type 2 diabetes in adults.” In pediatrics, the only licensed treatments that have been available until recently were metformin and insulin, with the latter being an “illogical treatment to treat those with obesity-related diabetes.” The study’s findings, however, support liraglutide as another option to consider, said Dr. Barrett, a pediatric endocrinologist and professor of pediatrics and child health based at the University of Birmingham, England.

“Liraglutide at doses of up to 1.8 mg/day when added to metformin, and basal insulin if required, does seem to offer an additional treatment option for children and young people with type 2 diabetes who require improved glycemic control after they’ve reached a maximum dose of metformin,” he said.

ELLIPSE (Evaluation of Liraglutide in Pediatrics with Diabetes) was a multicenter, randomized, parallel group, placebo-controlled trial to assess the efficacy and safety of liraglutide as an add-on treatment to metformin, with or without basal insulin, in 134 overweight or obese children and adolescents (aged 10-17) with type 2 diabetes.

For inclusion, patients had to be able to complete the trial before their 18th birthday, and have an HbA_1c of at least 7% if being treated with diet and exercise, or 6.5% or higher if already being treated with metformin, with or without insulin. Body mass index had to be above the 85the percentile for their age and sex.

Of 307 children and adolescents screened at 84 centers in 25 countries, 135 were randomized and 134 were treated between 2012 and 2018. Screening took place over a period of 2 weeks, after which time those eligible for the trial underwent a 3- to 4-week period where their dose of metformin was titrated if needed followed by an 8-week maintenance period. Only after that was randomization to liraglutide or placebo done, with the GLP-1R started at a subcutaneous dose of 0.6 mg and titrated up to 1.2 or 1.8 mg over 3 days to achieve a fasting plasma glucose (FPG) of less than 6.1 mmol/L (110 mg/dL). However, not all patients were escalated to the top dose, Dr. Barrett noted.

The mean age of patients in the trial was 14.5 years; about 60% of patients were female. The duration of diabetes was about 1.9 years and the average body weight and BMI a respective 91 kg and 33 kg/m².

Over the course of the study, FPG fell by 1.06 mmol/L at week 26 and 1.03 mmol/L at week 52 in the liraglutide group but rose in the placebo group by 0.80 and 0.78 mmol/L, respectively. The estimated treatment difference was –1.88 (P = .002) and –1.81 at 26 an 52 weeks, respectively.

What was “a really gratifying to see,” said Dr. Barrett, was that the proportion of children and young people achieving a glycemic target of an HbA_1c of less than 7% by the end of the double-blind treatment period was significantly higher in the liraglutide than placebo group, at 63.7% and 36.5%, respectively.

Most of the adverse effects seen in the study were gastrointestinal symptoms, including nausea, vomiting, and diarrhea, in about 20% of liraglutide-treated patients, compared with roughly 10% of placebo-treated patients. “This is really reflected in the adult studies as well, and many of these were thankfully transient.”

As for hypoglycemia, Dr. Barrett reported that there was a higher rate in liraglutide- than placebo-treated patients (45.5% vs. 25% for any event), although there were no severe episodes in the liraglutide group and one in the placebo group. Almost a third (31%) of hypoglycemic episodes were asymptomatic, versus 17.6% for the placebo group.

“This is the first successfully completed phase 3 trial showing efficacy of a noninsulin agent, in this case, for children who do not get managed solely on metformin monotherapy,” Dr. Barrett said.

The Food and Drug Administration has approved liraglutide for use in pediatric patients 10 years or older with type 2 diabetes, based in part on results of the ELLIPSE results, Novo Nordisk announced in June. The trial results were published prior to the EASD meeting (Tamborlane WV et al. N Engl J Med. 2019 Aug 15;381:637-46).

Novo Nordisk initiated and funded the trial, and most of the investigators reported receiving funds from the company outside the submitted work. Dr Barrett disclosed being a consultant to and/or receiving honoraria from AstraZeneca, Novo Nordisk and Servier.

SOURCE: Barrett T et al. EASD 2019. Abstract 84.

BARCELONA – The glucagon-like peptide-1 receptor agonist (GLP-1 RA) liraglutide added onto metformin with or without basal insulin effectively reduced hemoglobin A_1c and fasting plasma glucose levels in children with type 2 diabetes in the 52-week ELLIPSE study.

Sara Freeman/MDedge News

The primary endpoint of the trial, which was the mean change in HbA_1c from baseline to 26 weeks, was met, with a greater percentage point decrease with liraglutide (Victoza) than placebo (–0.64 vs. +0.42), with an estimated treatment difference of –1.06 percentage points (P less than .001). At the end of the study, the percentage point changes were –0.50 and +0.80, with a between-group difference of –1.30 in favor of liraglutide.

“Those of us working in pediatric practice are seeing an increasing demand for our clinical services in children with type 2 diabetes,” study investigator Timothy Barrett, PhD, MBBS, observed at the annual meeting of the European Association for the Study of Diabetes. This reflects the increasing prevalence of type 2 diabetes in this age group and is most likely linked to the rising rates of obesity and overweight that have been reported widely in young people in recent years, he added.

“Unfortunately, we look with envy upon our adult physician colleagues, and the range of treatments they have available to treat type 2 diabetes in adults.” In pediatrics, the only licensed treatments that have been available until recently were metformin and insulin, with the latter being an “illogical treatment to treat those with obesity-related diabetes.” The study’s findings, however, support liraglutide as another option to consider, said Dr. Barrett, a pediatric endocrinologist and professor of pediatrics and child health based at the University of Birmingham, England.

“Liraglutide at doses of up to 1.8 mg/day when added to metformin, and basal insulin if required, does seem to offer an additional treatment option for children and young people with type 2 diabetes who require improved glycemic control after they’ve reached a maximum dose of metformin,” he said.

ELLIPSE (Evaluation of Liraglutide in Pediatrics with Diabetes) was a multicenter, randomized, parallel group, placebo-controlled trial to assess the efficacy and safety of liraglutide as an add-on treatment to metformin, with or without basal insulin, in 134 overweight or obese children and adolescents (aged 10-17) with type 2 diabetes.

For inclusion, patients had to be able to complete the trial before their 18th birthday, and have an HbA_1c of at least 7% if being treated with diet and exercise, or 6.5% or higher if already being treated with metformin, with or without insulin. Body mass index had to be above the 85the percentile for their age and sex.

Of 307 children and adolescents screened at 84 centers in 25 countries, 135 were randomized and 134 were treated between 2012 and 2018. Screening took place over a period of 2 weeks, after which time those eligible for the trial underwent a 3- to 4-week period where their dose of metformin was titrated if needed followed by an 8-week maintenance period. Only after that was randomization to liraglutide or placebo done, with the GLP-1R started at a subcutaneous dose of 0.6 mg and titrated up to 1.2 or 1.8 mg over 3 days to achieve a fasting plasma glucose (FPG) of less than 6.1 mmol/L (110 mg/dL). However, not all patients were escalated to the top dose, Dr. Barrett noted.

The mean age of patients in the trial was 14.5 years; about 60% of patients were female. The duration of diabetes was about 1.9 years and the average body weight and BMI a respective 91 kg and 33 kg/m².

Over the course of the study, FPG fell by 1.06 mmol/L at week 26 and 1.03 mmol/L at week 52 in the liraglutide group but rose in the placebo group by 0.80 and 0.78 mmol/L, respectively. The estimated treatment difference was –1.88 (P = .002) and –1.81 at 26 an 52 weeks, respectively.

What was “a really gratifying to see,” said Dr. Barrett, was that the proportion of children and young people achieving a glycemic target of an HbA_1c of less than 7% by the end of the double-blind treatment period was significantly higher in the liraglutide than placebo group, at 63.7% and 36.5%, respectively.

Most of the adverse effects seen in the study were gastrointestinal symptoms, including nausea, vomiting, and diarrhea, in about 20% of liraglutide-treated patients, compared with roughly 10% of placebo-treated patients. “This is really reflected in the adult studies as well, and many of these were thankfully transient.”

As for hypoglycemia, Dr. Barrett reported that there was a higher rate in liraglutide- than placebo-treated patients (45.5% vs. 25% for any event), although there were no severe episodes in the liraglutide group and one in the placebo group. Almost a third (31%) of hypoglycemic episodes were asymptomatic, versus 17.6% for the placebo group.

“This is the first successfully completed phase 3 trial showing efficacy of a noninsulin agent, in this case, for children who do not get managed solely on metformin monotherapy,” Dr. Barrett said.

The Food and Drug Administration has approved liraglutide for use in pediatric patients 10 years or older with type 2 diabetes, based in part on results of the ELLIPSE results, Novo Nordisk announced in June. The trial results were published prior to the EASD meeting (Tamborlane WV et al. N Engl J Med. 2019 Aug 15;381:637-46).

Novo Nordisk initiated and funded the trial, and most of the investigators reported receiving funds from the company outside the submitted work. Dr Barrett disclosed being a consultant to and/or receiving honoraria from AstraZeneca, Novo Nordisk and Servier.

SOURCE: Barrett T et al. EASD 2019. Abstract 84.

PARIS – All lifestyle-related cardiovascular risk factors aren’t equal in power when it comes to secondary prevention after a first acute MI, according to a massive Swedish registry study.

Insufficient physical activity and current smoking were consistently the strongest risk factors for all-cause mortality, major adverse cardiovascular events, and other key adverse outcomes in an analysis from the SWEDEHEART registry. The study included 65,002 patients discharged after a first MI and 325,010 age- and sex-matched controls with no prior MI followed for a median of 5.5 years and maximum of 12, Emil Hagstrom, MD, PhD, reported at the annual congress of the European Society of Cardiology.

Strongest lifestyle risk factors

The study examined the long-term relative importance of control of six major lifestyle risk factors for secondary cardiovascular prevention: current smoking, insufficient physical activity, blood pressure of 140/90 mm Hg or more, obesity, a fasting blood glucose of at least 126 mg/dL, and an LDL cholesterol of 70 mg/dL or more. Notably, two risk factors that physicians often emphasize in working with their patients with known coronary heart disease – an elevated LDL cholesterol and obesity – barely moved the needle. Out of the six risk factors scrutinized, those two consistently showed the weakest association with long-term risk of adverse outcomes. Occupying the middle ground in terms of predictive strength were hypertension and elevated blood glucose, according to Dr. Hagstrom, a cardiologist at Uppsala (Sweden) University.

Risk factor status was assessed 6-10 weeks post MI. Insufficient physical activity was defined as not engaging in at least 30 minutes of moderate-intensity exercise on at least 5 days per week. And when Dr. Hagstrom recalculated the risk of adverse outcomes using an LDL cholesterol threshold of 55 mg/dL rather than using 70 mg/dL, as recommended in new ESC secondary prevention guidelines released during the congress, the study results remained unchanged.

Cumulative effects

A key SWEDEHEART finding underscoring the importance of lifestyle in secondary prevention was that a linear stepwise relationship existed between the number of risk factors at target levels and the risk of all of the various adverse outcomes assessed, including stroke and heart failure hospitalization as well as all-cause mortality, cardiovascular mortality, and major bleeding.

Moreover, patients with none of the six risk factors outside of target when assessed after their MI had the same risks of all-cause mortality, cardiovascular mortality, and stroke as the matched controls.

For example, in an analysis adjusted for comorbid cancer, chronic obstructive pulmonary disease, and dementia, post-MI patients with zero risk factors had the same long-term risk of cardiovascular mortality as controls without a history of MI at baseline. With one risk factor not at target, a patient had a 41% increased risk compared with controls, a statistically significant difference. With two out-of-whack risk factors, the risk climbed to 102%. With three, 185%. With four risk factors not at target, the all-cause mortality risk jumped to 291%. And patients with more than four of the six risk factors not at target had a 409% greater risk of all-cause mortality than controls who had never had a heart attack.

When Dr. Hagstrom stratified subjects by age at baseline – up to 55, 56-64, 65-70, and 70-75 years – he discovered that, regardless of age, patients with zero risk factors had the same risk of all-cause mortality and other adverse outcomes as controls. However, when risk factors were present, younger patients consistently had a higher risk of all adverse outcomes than older patients with the same number of risk factors. When asked for an explanation of this phenomenon, Dr. Hagstrom noted that younger patients with multiple risk factors have a longer time to be exposed to and accumulate risk.

Follow-up of the study cohort will continue for years to come, the cardiologist promised.

At an ESC congress highlights session that closed out the meeting, Eva Prescott, MD, put the SWEDEHEART study at the top of her list of important developments in preventive cardiology arising from the congress.

“This is an excellent national registry I think we’re all envious of,” commented Dr. Prescott, a cardiologist at Copenhagen University. “The conclusion of this registry-based data, I think, is that lifestyle really remains at the core of prevention of cardiovascular events still today.”

The SWEDEHEART study analysis was funded free of commercial support. Dr. Hagstrom reported serving as a consultant to or receiving speakers’ fees from Amgen, AstraZeneca, Bayer, Novo Nordisk, and Sanofi.

[email protected]

PARIS – All lifestyle-related cardiovascular risk factors aren’t equal in power when it comes to secondary prevention after a first acute MI, according to a massive Swedish registry study.

Insufficient physical activity and current smoking were consistently the strongest risk factors for all-cause mortality, major adverse cardiovascular events, and other key adverse outcomes in an analysis from the SWEDEHEART registry. The study included 65,002 patients discharged after a first MI and 325,010 age- and sex-matched controls with no prior MI followed for a median of 5.5 years and maximum of 12, Emil Hagstrom, MD, PhD, reported at the annual congress of the European Society of Cardiology.

Strongest lifestyle risk factors

The study examined the long-term relative importance of control of six major lifestyle risk factors for secondary cardiovascular prevention: current smoking, insufficient physical activity, blood pressure of 140/90 mm Hg or more, obesity, a fasting blood glucose of at least 126 mg/dL, and an LDL cholesterol of 70 mg/dL or more. Notably, two risk factors that physicians often emphasize in working with their patients with known coronary heart disease – an elevated LDL cholesterol and obesity – barely moved the needle. Out of the six risk factors scrutinized, those two consistently showed the weakest association with long-term risk of adverse outcomes. Occupying the middle ground in terms of predictive strength were hypertension and elevated blood glucose, according to Dr. Hagstrom, a cardiologist at Uppsala (Sweden) University.

Risk factor status was assessed 6-10 weeks post MI. Insufficient physical activity was defined as not engaging in at least 30 minutes of moderate-intensity exercise on at least 5 days per week. And when Dr. Hagstrom recalculated the risk of adverse outcomes using an LDL cholesterol threshold of 55 mg/dL rather than using 70 mg/dL, as recommended in new ESC secondary prevention guidelines released during the congress, the study results remained unchanged.

Cumulative effects

A key SWEDEHEART finding underscoring the importance of lifestyle in secondary prevention was that a linear stepwise relationship existed between the number of risk factors at target levels and the risk of all of the various adverse outcomes assessed, including stroke and heart failure hospitalization as well as all-cause mortality, cardiovascular mortality, and major bleeding.

Moreover, patients with none of the six risk factors outside of target when assessed after their MI had the same risks of all-cause mortality, cardiovascular mortality, and stroke as the matched controls.

For example, in an analysis adjusted for comorbid cancer, chronic obstructive pulmonary disease, and dementia, post-MI patients with zero risk factors had the same long-term risk of cardiovascular mortality as controls without a history of MI at baseline. With one risk factor not at target, a patient had a 41% increased risk compared with controls, a statistically significant difference. With two out-of-whack risk factors, the risk climbed to 102%. With three, 185%. With four risk factors not at target, the all-cause mortality risk jumped to 291%. And patients with more than four of the six risk factors not at target had a 409% greater risk of all-cause mortality than controls who had never had a heart attack.

When Dr. Hagstrom stratified subjects by age at baseline – up to 55, 56-64, 65-70, and 70-75 years – he discovered that, regardless of age, patients with zero risk factors had the same risk of all-cause mortality and other adverse outcomes as controls. However, when risk factors were present, younger patients consistently had a higher risk of all adverse outcomes than older patients with the same number of risk factors. When asked for an explanation of this phenomenon, Dr. Hagstrom noted that younger patients with multiple risk factors have a longer time to be exposed to and accumulate risk.

Follow-up of the study cohort will continue for years to come, the cardiologist promised.

At an ESC congress highlights session that closed out the meeting, Eva Prescott, MD, put the SWEDEHEART study at the top of her list of important developments in preventive cardiology arising from the congress.

“This is an excellent national registry I think we’re all envious of,” commented Dr. Prescott, a cardiologist at Copenhagen University. “The conclusion of this registry-based data, I think, is that lifestyle really remains at the core of prevention of cardiovascular events still today.”

The SWEDEHEART study analysis was funded free of commercial support. Dr. Hagstrom reported serving as a consultant to or receiving speakers’ fees from Amgen, AstraZeneca, Bayer, Novo Nordisk, and Sanofi.

[email protected]

PARIS – All lifestyle-related cardiovascular risk factors aren’t equal in power when it comes to secondary prevention after a first acute MI, according to a massive Swedish registry study.

Insufficient physical activity and current smoking were consistently the strongest risk factors for all-cause mortality, major adverse cardiovascular events, and other key adverse outcomes in an analysis from the SWEDEHEART registry. The study included 65,002 patients discharged after a first MI and 325,010 age- and sex-matched controls with no prior MI followed for a median of 5.5 years and maximum of 12, Emil Hagstrom, MD, PhD, reported at the annual congress of the European Society of Cardiology.

Strongest lifestyle risk factors

The study examined the long-term relative importance of control of six major lifestyle risk factors for secondary cardiovascular prevention: current smoking, insufficient physical activity, blood pressure of 140/90 mm Hg or more, obesity, a fasting blood glucose of at least 126 mg/dL, and an LDL cholesterol of 70 mg/dL or more. Notably, two risk factors that physicians often emphasize in working with their patients with known coronary heart disease – an elevated LDL cholesterol and obesity – barely moved the needle. Out of the six risk factors scrutinized, those two consistently showed the weakest association with long-term risk of adverse outcomes. Occupying the middle ground in terms of predictive strength were hypertension and elevated blood glucose, according to Dr. Hagstrom, a cardiologist at Uppsala (Sweden) University.

Risk factor status was assessed 6-10 weeks post MI. Insufficient physical activity was defined as not engaging in at least 30 minutes of moderate-intensity exercise on at least 5 days per week. And when Dr. Hagstrom recalculated the risk of adverse outcomes using an LDL cholesterol threshold of 55 mg/dL rather than using 70 mg/dL, as recommended in new ESC secondary prevention guidelines released during the congress, the study results remained unchanged.

Cumulative effects

A key SWEDEHEART finding underscoring the importance of lifestyle in secondary prevention was that a linear stepwise relationship existed between the number of risk factors at target levels and the risk of all of the various adverse outcomes assessed, including stroke and heart failure hospitalization as well as all-cause mortality, cardiovascular mortality, and major bleeding.

Moreover, patients with none of the six risk factors outside of target when assessed after their MI had the same risks of all-cause mortality, cardiovascular mortality, and stroke as the matched controls.

For example, in an analysis adjusted for comorbid cancer, chronic obstructive pulmonary disease, and dementia, post-MI patients with zero risk factors had the same long-term risk of cardiovascular mortality as controls without a history of MI at baseline. With one risk factor not at target, a patient had a 41% increased risk compared with controls, a statistically significant difference. With two out-of-whack risk factors, the risk climbed to 102%. With three, 185%. With four risk factors not at target, the all-cause mortality risk jumped to 291%. And patients with more than four of the six risk factors not at target had a 409% greater risk of all-cause mortality than controls who had never had a heart attack.

When Dr. Hagstrom stratified subjects by age at baseline – up to 55, 56-64, 65-70, and 70-75 years – he discovered that, regardless of age, patients with zero risk factors had the same risk of all-cause mortality and other adverse outcomes as controls. However, when risk factors were present, younger patients consistently had a higher risk of all adverse outcomes than older patients with the same number of risk factors. When asked for an explanation of this phenomenon, Dr. Hagstrom noted that younger patients with multiple risk factors have a longer time to be exposed to and accumulate risk.

Follow-up of the study cohort will continue for years to come, the cardiologist promised.

At an ESC congress highlights session that closed out the meeting, Eva Prescott, MD, put the SWEDEHEART study at the top of her list of important developments in preventive cardiology arising from the congress.

“This is an excellent national registry I think we’re all envious of,” commented Dr. Prescott, a cardiologist at Copenhagen University. “The conclusion of this registry-based data, I think, is that lifestyle really remains at the core of prevention of cardiovascular events still today.”

The SWEDEHEART study analysis was funded free of commercial support. Dr. Hagstrom reported serving as a consultant to or receiving speakers’ fees from Amgen, AstraZeneca, Bayer, Novo Nordisk, and Sanofi.

[email protected]

People who eat red meat or processed meat should continue their current meat consumption, according to recent guidelines from an international panel that were recently published in the Annals of Internal Medicine.

Fuse/Thinkstock

This recommendation was based on the panel having found “low- to very-low-certainty evidence that diets lower in unprocessed red meat may have little or no effect on the risk for major cardiometabolic outcomes and cancer mortality and incidence.” Additionally, meta-analysis results from 23 cohort studies provided low- to very-low-certainty evidence that decreasing unprocessed red meat intake may result in a very small reduction in the risk for major cardiovascular outcomes and type 2 diabetes, with no statistically differences in all-cause mortality and cardiovascular mortality, the guidelines say.

“Our weak recommendation that people continue their current meat consumption highlights both the uncertainty associated with possible harmful effects and the very small magnitude of effect, even if the best estimates represent true causation, which we believe to be implausible,” Bradley C. Johnston, PhD, of the department of community health and epidemiology at Dalhousie University, Halifax, N.S., and colleagues wrote in their paper summarizing the panel’s guidelines.

The evidence Dr. Johnston and colleagues examined were from four systematic reviews analyzing the health effects of red meat and processed meat consumption in randomized trials and meta-analyses of cohort studies as well as one systematic review that identified how people viewed their consumption of meat and values surrounding meat consumption.

In one review of 12 randomized trials examining diets of high and low red meat consumption, a diet consisting of low red meat had little effect on cardiovascular mortality (hazard ratio, 0.98; 95% confidence interval, 0.91-1.06), cardiovascular disease (HR, 0.99; 95% CI, 0.94-1.05), all-cause mortality (0.99; 95% CI, 0.95-1.03) and total cancer mortality (HR, 0.95; 95% CI, 0.89-1.01), including on colorectal cancer or breast cancer (Zeraatkar D et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0622). A different review of observational cohort studies with more than 1,000 participants found “very-small or possibly small decreases” in all-cause mortality, incidence, and all-cause mortality of cancer, cardiovascular mortality, nonfatal coronary heart disease and MI, and type 2 diabetes for patients who had a diet low in red meat or processed meat (Vernooij R et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1583); a second review by Zeraatkar and colleagues of 55 observational cohort studies with more than 4 million participants found three servings of unprocessed red meat and processed meat per week was associated with a “very small reduction” in risk for MI, stroke, type 2 diabetes, cardiovascular mortality, and all-cause mortality (Zeraatkar D et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1326). Another systematic review of 56 observational cohort studies found three servings of unprocessed red meat per week was associated with a slight reduction in overall cancer mortality (Han MA et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0699).

The authors also performed a systematic review of participant preferences and values regarding meat consumption. The evidence from 54 qualitative studies showed omnivores preferred eating meat, considered it part of a healthy diet, “lack[ed] the skills needed” to prepare meals without meat, and were mostly unwilling to change their meat consumption (Valli C et al. Ann Intern Med. 2019. doi: 10.7326/M19-1326).

“There was a very small and often trivial absolute risk reduction based on a realistic decrease of three servings of red or processed meat per week,” Dr. Johnston and colleagues wrote in their guidelines. If the very-small exposure effect is true, given peoples’ attachment to their meat-based diet, the associated risk reduction is not likely to provide sufficient motivation to reduce consumption of red meat or processed meat in fully informed individuals, and the weak, rather than strong, recommendation is based on the large variability in peoples’ values and preferences related to meat.”

The authors noted they did not examine factors such as cost, acceptability, feasibility, equity, environmental impact, and views on animal welfare when creating the guidelines. In addition, the low level of evidence from the randomized trials and observational studies means that the potential benefits of reducing red meat or processed meat intake may not outweigh the cultural and personal preferences or quality of life issues that could arise from changing one’s diet.

“This assessment may be excessively pessimistic; indeed, we hope that is the case,” they said. “What is certain is that generating higher-quality evidence regarding the magnitude of any causal effect of meat consumption on health outcomes will test the ingenuity and imagination of health science investigators.”

Dr. El Dib reported receiving funding from the São Paulo Research Foundation, the National Council for Scientific and Technological Development, and the faculty of medicine at Dalhousie University. Dr. de Souza reports relationships with the Canadian Institutes of Health Research/Health Canada, the Canadian Foundation for Dietetic Research and the World Health Organization in the forms of personal fees, grants, and speakers bureau and board of directorship appointments. Dr. Patel reports receiving grants and person fees from the National Institutes of Health, Sanofi, the National Science Foundation, XY.health, doc.ai, Janssen, and the CDC.

SOURCE: Johnston B et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1621.

People who eat red meat or processed meat should continue their current meat consumption, according to recent guidelines from an international panel that were recently published in the Annals of Internal Medicine.

Fuse/Thinkstock

This recommendation was based on the panel having found “low- to very-low-certainty evidence that diets lower in unprocessed red meat may have little or no effect on the risk for major cardiometabolic outcomes and cancer mortality and incidence.” Additionally, meta-analysis results from 23 cohort studies provided low- to very-low-certainty evidence that decreasing unprocessed red meat intake may result in a very small reduction in the risk for major cardiovascular outcomes and type 2 diabetes, with no statistically differences in all-cause mortality and cardiovascular mortality, the guidelines say.

“Our weak recommendation that people continue their current meat consumption highlights both the uncertainty associated with possible harmful effects and the very small magnitude of effect, even if the best estimates represent true causation, which we believe to be implausible,” Bradley C. Johnston, PhD, of the department of community health and epidemiology at Dalhousie University, Halifax, N.S., and colleagues wrote in their paper summarizing the panel’s guidelines.

The evidence Dr. Johnston and colleagues examined were from four systematic reviews analyzing the health effects of red meat and processed meat consumption in randomized trials and meta-analyses of cohort studies as well as one systematic review that identified how people viewed their consumption of meat and values surrounding meat consumption.

In one review of 12 randomized trials examining diets of high and low red meat consumption, a diet consisting of low red meat had little effect on cardiovascular mortality (hazard ratio, 0.98; 95% confidence interval, 0.91-1.06), cardiovascular disease (HR, 0.99; 95% CI, 0.94-1.05), all-cause mortality (0.99; 95% CI, 0.95-1.03) and total cancer mortality (HR, 0.95; 95% CI, 0.89-1.01), including on colorectal cancer or breast cancer (Zeraatkar D et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0622). A different review of observational cohort studies with more than 1,000 participants found “very-small or possibly small decreases” in all-cause mortality, incidence, and all-cause mortality of cancer, cardiovascular mortality, nonfatal coronary heart disease and MI, and type 2 diabetes for patients who had a diet low in red meat or processed meat (Vernooij R et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1583); a second review by Zeraatkar and colleagues of 55 observational cohort studies with more than 4 million participants found three servings of unprocessed red meat and processed meat per week was associated with a “very small reduction” in risk for MI, stroke, type 2 diabetes, cardiovascular mortality, and all-cause mortality (Zeraatkar D et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1326). Another systematic review of 56 observational cohort studies found three servings of unprocessed red meat per week was associated with a slight reduction in overall cancer mortality (Han MA et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0699).

The authors also performed a systematic review of participant preferences and values regarding meat consumption. The evidence from 54 qualitative studies showed omnivores preferred eating meat, considered it part of a healthy diet, “lack[ed] the skills needed” to prepare meals without meat, and were mostly unwilling to change their meat consumption (Valli C et al. Ann Intern Med. 2019. doi: 10.7326/M19-1326).

“There was a very small and often trivial absolute risk reduction based on a realistic decrease of three servings of red or processed meat per week,” Dr. Johnston and colleagues wrote in their guidelines. If the very-small exposure effect is true, given peoples’ attachment to their meat-based diet, the associated risk reduction is not likely to provide sufficient motivation to reduce consumption of red meat or processed meat in fully informed individuals, and the weak, rather than strong, recommendation is based on the large variability in peoples’ values and preferences related to meat.”

The authors noted they did not examine factors such as cost, acceptability, feasibility, equity, environmental impact, and views on animal welfare when creating the guidelines. In addition, the low level of evidence from the randomized trials and observational studies means that the potential benefits of reducing red meat or processed meat intake may not outweigh the cultural and personal preferences or quality of life issues that could arise from changing one’s diet.

“This assessment may be excessively pessimistic; indeed, we hope that is the case,” they said. “What is certain is that generating higher-quality evidence regarding the magnitude of any causal effect of meat consumption on health outcomes will test the ingenuity and imagination of health science investigators.”

Dr. El Dib reported receiving funding from the São Paulo Research Foundation, the National Council for Scientific and Technological Development, and the faculty of medicine at Dalhousie University. Dr. de Souza reports relationships with the Canadian Institutes of Health Research/Health Canada, the Canadian Foundation for Dietetic Research and the World Health Organization in the forms of personal fees, grants, and speakers bureau and board of directorship appointments. Dr. Patel reports receiving grants and person fees from the National Institutes of Health, Sanofi, the National Science Foundation, XY.health, doc.ai, Janssen, and the CDC.

SOURCE: Johnston B et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1621.

People who eat red meat or processed meat should continue their current meat consumption, according to recent guidelines from an international panel that were recently published in the Annals of Internal Medicine.

Fuse/Thinkstock

This recommendation was based on the panel having found “low- to very-low-certainty evidence that diets lower in unprocessed red meat may have little or no effect on the risk for major cardiometabolic outcomes and cancer mortality and incidence.” Additionally, meta-analysis results from 23 cohort studies provided low- to very-low-certainty evidence that decreasing unprocessed red meat intake may result in a very small reduction in the risk for major cardiovascular outcomes and type 2 diabetes, with no statistically differences in all-cause mortality and cardiovascular mortality, the guidelines say.

“Our weak recommendation that people continue their current meat consumption highlights both the uncertainty associated with possible harmful effects and the very small magnitude of effect, even if the best estimates represent true causation, which we believe to be implausible,” Bradley C. Johnston, PhD, of the department of community health and epidemiology at Dalhousie University, Halifax, N.S., and colleagues wrote in their paper summarizing the panel’s guidelines.

The evidence Dr. Johnston and colleagues examined were from four systematic reviews analyzing the health effects of red meat and processed meat consumption in randomized trials and meta-analyses of cohort studies as well as one systematic review that identified how people viewed their consumption of meat and values surrounding meat consumption.

In one review of 12 randomized trials examining diets of high and low red meat consumption, a diet consisting of low red meat had little effect on cardiovascular mortality (hazard ratio, 0.98; 95% confidence interval, 0.91-1.06), cardiovascular disease (HR, 0.99; 95% CI, 0.94-1.05), all-cause mortality (0.99; 95% CI, 0.95-1.03) and total cancer mortality (HR, 0.95; 95% CI, 0.89-1.01), including on colorectal cancer or breast cancer (Zeraatkar D et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0622). A different review of observational cohort studies with more than 1,000 participants found “very-small or possibly small decreases” in all-cause mortality, incidence, and all-cause mortality of cancer, cardiovascular mortality, nonfatal coronary heart disease and MI, and type 2 diabetes for patients who had a diet low in red meat or processed meat (Vernooij R et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1583); a second review by Zeraatkar and colleagues of 55 observational cohort studies with more than 4 million participants found three servings of unprocessed red meat and processed meat per week was associated with a “very small reduction” in risk for MI, stroke, type 2 diabetes, cardiovascular mortality, and all-cause mortality (Zeraatkar D et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1326). Another systematic review of 56 observational cohort studies found three servings of unprocessed red meat per week was associated with a slight reduction in overall cancer mortality (Han MA et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-0699).

The authors also performed a systematic review of participant preferences and values regarding meat consumption. The evidence from 54 qualitative studies showed omnivores preferred eating meat, considered it part of a healthy diet, “lack[ed] the skills needed” to prepare meals without meat, and were mostly unwilling to change their meat consumption (Valli C et al. Ann Intern Med. 2019. doi: 10.7326/M19-1326).

“There was a very small and often trivial absolute risk reduction based on a realistic decrease of three servings of red or processed meat per week,” Dr. Johnston and colleagues wrote in their guidelines. If the very-small exposure effect is true, given peoples’ attachment to their meat-based diet, the associated risk reduction is not likely to provide sufficient motivation to reduce consumption of red meat or processed meat in fully informed individuals, and the weak, rather than strong, recommendation is based on the large variability in peoples’ values and preferences related to meat.”

The authors noted they did not examine factors such as cost, acceptability, feasibility, equity, environmental impact, and views on animal welfare when creating the guidelines. In addition, the low level of evidence from the randomized trials and observational studies means that the potential benefits of reducing red meat or processed meat intake may not outweigh the cultural and personal preferences or quality of life issues that could arise from changing one’s diet.

“This assessment may be excessively pessimistic; indeed, we hope that is the case,” they said. “What is certain is that generating higher-quality evidence regarding the magnitude of any causal effect of meat consumption on health outcomes will test the ingenuity and imagination of health science investigators.”

Dr. El Dib reported receiving funding from the São Paulo Research Foundation, the National Council for Scientific and Technological Development, and the faculty of medicine at Dalhousie University. Dr. de Souza reports relationships with the Canadian Institutes of Health Research/Health Canada, the Canadian Foundation for Dietetic Research and the World Health Organization in the forms of personal fees, grants, and speakers bureau and board of directorship appointments. Dr. Patel reports receiving grants and person fees from the National Institutes of Health, Sanofi, the National Science Foundation, XY.health, doc.ai, Janssen, and the CDC.

SOURCE: Johnston B et al. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1621.

The Food and Drug Administration has approved canagliflozin (Invokana) for the treatment of diabetic kidney disease and for reduction of the risk of hospitalization for heart failure in patients with type 2 diabetes and diabetic kidney disease, which makes it the first drug indicated for diabetic kidney disease treatment in 20 years.

FDA approval, which was announced in a press release by Janssen, the drug’s manufacturer, is based on results from the phase 3 CREDENCE trial. In that study patients with type 2 diabetes and chronic diabetic kidney disease received either 100 mg canagliflozin or placebo. Patients who received canagliflozin experienced a 30% reduction in the risk of the primary composite endpoint, which included end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death. The risk of secondary outcomes were also reduced in patients receiving canagliflozin, including a 39% reduction in the risk of hospitalization for heart failure.

The most common adverse events associated with canagliflozin, according to the label, are female genital mycotic infections, urinary tract infection, and increased urination. Serious adverse events associated with canagliflozin include ketoacidosis, kidney problems, serious urinary tract infections, hypoglycemia, necrotizing fasciitis, serious allergic reaction, and bone fractures.

“The real battle to turn the tide on kidney disease is in early detection and slowing its progression so that patients stay healthier and fewer patients reach kidney failure,” LaVerne A. Burton, president and CEO of the American Kidney Fund, said in the press release. “We are so grateful that advances in kidney disease research are producing treatment options that help to slow the progression of diabetic kidney disease and reduce the risk of hospitalization for heart failure.”

Find the full press release on the Janssen website.

[email protected]

The Food and Drug Administration has approved canagliflozin (Invokana) for the treatment of diabetic kidney disease and for reduction of the risk of hospitalization for heart failure in patients with type 2 diabetes and diabetic kidney disease, which makes it the first drug indicated for diabetic kidney disease treatment in 20 years.

FDA approval, which was announced in a press release by Janssen, the drug’s manufacturer, is based on results from the phase 3 CREDENCE trial. In that study patients with type 2 diabetes and chronic diabetic kidney disease received either 100 mg canagliflozin or placebo. Patients who received canagliflozin experienced a 30% reduction in the risk of the primary composite endpoint, which included end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death. The risk of secondary outcomes were also reduced in patients receiving canagliflozin, including a 39% reduction in the risk of hospitalization for heart failure.

The most common adverse events associated with canagliflozin, according to the label, are female genital mycotic infections, urinary tract infection, and increased urination. Serious adverse events associated with canagliflozin include ketoacidosis, kidney problems, serious urinary tract infections, hypoglycemia, necrotizing fasciitis, serious allergic reaction, and bone fractures.

“The real battle to turn the tide on kidney disease is in early detection and slowing its progression so that patients stay healthier and fewer patients reach kidney failure,” LaVerne A. Burton, president and CEO of the American Kidney Fund, said in the press release. “We are so grateful that advances in kidney disease research are producing treatment options that help to slow the progression of diabetic kidney disease and reduce the risk of hospitalization for heart failure.”

Find the full press release on the Janssen website.

[email protected]

The Food and Drug Administration has approved canagliflozin (Invokana) for the treatment of diabetic kidney disease and for reduction of the risk of hospitalization for heart failure in patients with type 2 diabetes and diabetic kidney disease, which makes it the first drug indicated for diabetic kidney disease treatment in 20 years.

FDA approval, which was announced in a press release by Janssen, the drug’s manufacturer, is based on results from the phase 3 CREDENCE trial. In that study patients with type 2 diabetes and chronic diabetic kidney disease received either 100 mg canagliflozin or placebo. Patients who received canagliflozin experienced a 30% reduction in the risk of the primary composite endpoint, which included end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death. The risk of secondary outcomes were also reduced in patients receiving canagliflozin, including a 39% reduction in the risk of hospitalization for heart failure.

The most common adverse events associated with canagliflozin, according to the label, are female genital mycotic infections, urinary tract infection, and increased urination. Serious adverse events associated with canagliflozin include ketoacidosis, kidney problems, serious urinary tract infections, hypoglycemia, necrotizing fasciitis, serious allergic reaction, and bone fractures.

“The real battle to turn the tide on kidney disease is in early detection and slowing its progression so that patients stay healthier and fewer patients reach kidney failure,” LaVerne A. Burton, president and CEO of the American Kidney Fund, said in the press release. “We are so grateful that advances in kidney disease research are producing treatment options that help to slow the progression of diabetic kidney disease and reduce the risk of hospitalization for heart failure.”

Find the full press release on the Janssen website.

[email protected]

BARCELONA – Real-time continuous glucose monitoring (rtCGM) was better than self-monitoring of blood glucose (SMBG) in reducing hemoglobin A_1c (HbA1c) and other glycemic endpoints in people with type 1 diabetes, regardless of the type of insulin delivery method used in a 3-year follow-up of a prospective, real-world clinical trial.

Long-term results from the COMISAIR study showed that the end-of-study HbA_1c values were significantly lower, compared with baseline values, in people with type 1 diabetes who used rtCGM with multiple daily injections (MDI) of insulin (7.0% [53 mmol/mol], P = .0002) or an insulin pump (6.9% [52 mmol/mol], P less than .0001). There was no significant difference between the two rtCGM delivery-method groups.

Final HbA_1c values for those who used SMBG with multiple daily injections or an insulin pump were 8.0% (64 mmol/mol) and 7.7% (61 mmol/mol), respectively, but were not significantly different from baseline (P = .3574 and P = .1, respectively).

These findings could help guide physicians when discussing treatment and monitoring options with their patients, suggested study investigator Jan Šoupal, MD, PhD, of Charles University in Prague, when he presented the findings at the annual meeting of the European Association for the Study of Diabetes.

Dr. Šoupal and associates have previously reported data from the COMISAIR (Comparison of Different Treatment Modalities for Type 1 Diabetes Including Sensor-Augmented Insulin Regimens) study at 1 year of follow-up for 65 patients (Diabetes Technol Ther. 2016;18:532-8). The findings he presented at the EASD meeting, simultaneously published online in Diabetes Care, were for the full cohort of 94 patients and, with 3 years of follow-up, makes it “the longest CGM trial ever,” he said.

At the time the COMISAIR study was initiated, in 2013, “we knew that insulin pump therapy, especially in combination with real-time CGM, can improve several outcomes of patients with type 1 diabetes,” Dr. Šoupal observed. However, the effectiveness of CGM in patients with MDI was not widely described, and comparisons between continuous subcutaneous insulin infusion (CSII) and insulin MDI with rtCGM were lacking. “Moreover, we didn’t have any comparison between insulin pump therapy alone, without CGM, and MDI with CGM, and there were no long-term trials with real-time [continuous glucose monitoring].”

The aim of the COMISAIR study was therefore to compare four different treatment strategies in people with type 1 diabetes who had an HbA_1c of 7%-­­10% (53-86 mmol/mol), despite MDI treatment with insulin analogues and SMBG. The treatment strategies tested were CSII plus rtCGM (n = 26), MDI plus rtCGM (n = 22), CSII plus SMBG (n = 25), and MDI plus SMBG (n = 21). Patients were not randomized to these treatment arms but exposed to all of them during a 4-day DAFNE-like training session and then allowed to choose which they would like to use according to their individual needs and preferences, reflecting real-life practice.

Dr. Šoupal pointed out that two different continuous glucose monitoring devices had been used in the trial, and that 100% of the CGM groups wore a sensor for more than 70% of the time, which was one of the prerequisites for inclusion in the trial. Good adherence was observed, with 93% of patients completing all study visits, and CGM users wearing their sensors on average 88% of the time. “This nice adherence may be connected to the pretty good results,” he observed.

In discussing the HbA_1c results, Dr. Šoupal noted that “improvement observed in patients with [continuous glucose monitoring] is stable throughout 3 years, which is not always a reality for different types of treatment for diabetes.” In addition, “it is not so important how insulin is delivered, what is more important is how patients with type 1 diabetes monitor their glucose.”

Another key endpoint of the trial was time in range (70-180 mg/dL [3.9-10 mmol/L]). Results showed significantly more patients achieving this with rtCGM than with SMBG, regardless of whether they were using pump therapy or MDI. Comparing 3-year with baseline values, time in range was 72.3% versus 50.9% for rtCGM with CSII and 69% versus 48.7% for rtCGM with MDI (P less than .0001 for both). Results with SMBG with CSII or MDI were a respective 57.8% versus 50.6% (P = .0114) and 54.7% versus 51.8% (P = 1.0).

Glycemic variability was reduced in patients using insulin pumps with SBMG, and “not surprisingly, there was a reduction in both CGM-augmented groups,” Dr. Šoupal stated.

There was a reduction in the time spent in hypoglycemia from baseline to year 3 in all four groups, but that was significant only for the two rtCGM groups. Overall, there were seven severe hypoglycemia episodes, five in the SMBG groups (two in the CSII group, three in the MDI group) and two in the rtCGM groups (one each in the CSII and MDI groups), with one episode only occurring when the CGM sensor was not being worn.

Three episodes of ketoacidosis were reported – one each in the SMBG-pump, SMBG-MDI, and rtCGM-pump groups.

In summing up, Dr. Šoupal said that “real-time CGM, both with insulin pumps and with [multiple daily injections], provided significant, comparable, and stable improvement of glycemic outcomes.” He added that “treatment with CGM and MDI was more effective than treatment with insulin pump therapy alone, and that CGM and MDI can even be considered as a suitable alternative to treatment with insulin pumps and CMG for some patients.”

With many treatment options available, some will suit patients better than others, he suggested, but although “individualization of our treatment is important”, the COMISAIR data show that “it is CGM that makes the difference”.

The study was supported by the Agency for Healthcare Research and the Ministry of Health of the Czech Republic. Dr. Šoupal reported receiving honoraria from Abbott, AstraZeneca, Boehringer Ingelheim, Dexcom, Eli Lilly, Medtronic, Novo Nordisk, and Roche. Dexcom also paid for the development of the manuscript published in Diabetes Care.
 

SOURCES: Šoupal J et al. EASD 2019, Abstract 40; Šoupal J et al. Diabetes Care. 2019 Sep 17. doi: 10.2337/dc19-0888.

BARCELONA – Real-time continuous glucose monitoring (rtCGM) was better than self-monitoring of blood glucose (SMBG) in reducing hemoglobin A_1c (HbA1c) and other glycemic endpoints in people with type 1 diabetes, regardless of the type of insulin delivery method used in a 3-year follow-up of a prospective, real-world clinical trial.

Long-term results from the COMISAIR study showed that the end-of-study HbA_1c values were significantly lower, compared with baseline values, in people with type 1 diabetes who used rtCGM with multiple daily injections (MDI) of insulin (7.0% [53 mmol/mol], P = .0002) or an insulin pump (6.9% [52 mmol/mol], P less than .0001). There was no significant difference between the two rtCGM delivery-method groups.

Final HbA_1c values for those who used SMBG with multiple daily injections or an insulin pump were 8.0% (64 mmol/mol) and 7.7% (61 mmol/mol), respectively, but were not significantly different from baseline (P = .3574 and P = .1, respectively).

These findings could help guide physicians when discussing treatment and monitoring options with their patients, suggested study investigator Jan Šoupal, MD, PhD, of Charles University in Prague, when he presented the findings at the annual meeting of the European Association for the Study of Diabetes.

Dr. Šoupal and associates have previously reported data from the COMISAIR (Comparison of Different Treatment Modalities for Type 1 Diabetes Including Sensor-Augmented Insulin Regimens) study at 1 year of follow-up for 65 patients (Diabetes Technol Ther. 2016;18:532-8). The findings he presented at the EASD meeting, simultaneously published online in Diabetes Care, were for the full cohort of 94 patients and, with 3 years of follow-up, makes it “the longest CGM trial ever,” he said.

At the time the COMISAIR study was initiated, in 2013, “we knew that insulin pump therapy, especially in combination with real-time CGM, can improve several outcomes of patients with type 1 diabetes,” Dr. Šoupal observed. However, the effectiveness of CGM in patients with MDI was not widely described, and comparisons between continuous subcutaneous insulin infusion (CSII) and insulin MDI with rtCGM were lacking. “Moreover, we didn’t have any comparison between insulin pump therapy alone, without CGM, and MDI with CGM, and there were no long-term trials with real-time [continuous glucose monitoring].”

The aim of the COMISAIR study was therefore to compare four different treatment strategies in people with type 1 diabetes who had an HbA_1c of 7%-­­10% (53-86 mmol/mol), despite MDI treatment with insulin analogues and SMBG. The treatment strategies tested were CSII plus rtCGM (n = 26), MDI plus rtCGM (n = 22), CSII plus SMBG (n = 25), and MDI plus SMBG (n = 21). Patients were not randomized to these treatment arms but exposed to all of them during a 4-day DAFNE-like training session and then allowed to choose which they would like to use according to their individual needs and preferences, reflecting real-life practice.

Dr. Šoupal pointed out that two different continuous glucose monitoring devices had been used in the trial, and that 100% of the CGM groups wore a sensor for more than 70% of the time, which was one of the prerequisites for inclusion in the trial. Good adherence was observed, with 93% of patients completing all study visits, and CGM users wearing their sensors on average 88% of the time. “This nice adherence may be connected to the pretty good results,” he observed.

In discussing the HbA_1c results, Dr. Šoupal noted that “improvement observed in patients with [continuous glucose monitoring] is stable throughout 3 years, which is not always a reality for different types of treatment for diabetes.” In addition, “it is not so important how insulin is delivered, what is more important is how patients with type 1 diabetes monitor their glucose.”

Another key endpoint of the trial was time in range (70-180 mg/dL [3.9-10 mmol/L]). Results showed significantly more patients achieving this with rtCGM than with SMBG, regardless of whether they were using pump therapy or MDI. Comparing 3-year with baseline values, time in range was 72.3% versus 50.9% for rtCGM with CSII and 69% versus 48.7% for rtCGM with MDI (P less than .0001 for both). Results with SMBG with CSII or MDI were a respective 57.8% versus 50.6% (P = .0114) and 54.7% versus 51.8% (P = 1.0).

Glycemic variability was reduced in patients using insulin pumps with SBMG, and “not surprisingly, there was a reduction in both CGM-augmented groups,” Dr. Šoupal stated.

There was a reduction in the time spent in hypoglycemia from baseline to year 3 in all four groups, but that was significant only for the two rtCGM groups. Overall, there were seven severe hypoglycemia episodes, five in the SMBG groups (two in the CSII group, three in the MDI group) and two in the rtCGM groups (one each in the CSII and MDI groups), with one episode only occurring when the CGM sensor was not being worn.

Three episodes of ketoacidosis were reported – one each in the SMBG-pump, SMBG-MDI, and rtCGM-pump groups.

In summing up, Dr. Šoupal said that “real-time CGM, both with insulin pumps and with [multiple daily injections], provided significant, comparable, and stable improvement of glycemic outcomes.” He added that “treatment with CGM and MDI was more effective than treatment with insulin pump therapy alone, and that CGM and MDI can even be considered as a suitable alternative to treatment with insulin pumps and CMG for some patients.”

With many treatment options available, some will suit patients better than others, he suggested, but although “individualization of our treatment is important”, the COMISAIR data show that “it is CGM that makes the difference”.

The study was supported by the Agency for Healthcare Research and the Ministry of Health of the Czech Republic. Dr. Šoupal reported receiving honoraria from Abbott, AstraZeneca, Boehringer Ingelheim, Dexcom, Eli Lilly, Medtronic, Novo Nordisk, and Roche. Dexcom also paid for the development of the manuscript published in Diabetes Care.
 

SOURCES: Šoupal J et al. EASD 2019, Abstract 40; Šoupal J et al. Diabetes Care. 2019 Sep 17. doi: 10.2337/dc19-0888.

BARCELONA – Real-time continuous glucose monitoring (rtCGM) was better than self-monitoring of blood glucose (SMBG) in reducing hemoglobin A_1c (HbA1c) and other glycemic endpoints in people with type 1 diabetes, regardless of the type of insulin delivery method used in a 3-year follow-up of a prospective, real-world clinical trial.

Long-term results from the COMISAIR study showed that the end-of-study HbA_1c values were significantly lower, compared with baseline values, in people with type 1 diabetes who used rtCGM with multiple daily injections (MDI) of insulin (7.0% [53 mmol/mol], P = .0002) or an insulin pump (6.9% [52 mmol/mol], P less than .0001). There was no significant difference between the two rtCGM delivery-method groups.

Final HbA_1c values for those who used SMBG with multiple daily injections or an insulin pump were 8.0% (64 mmol/mol) and 7.7% (61 mmol/mol), respectively, but were not significantly different from baseline (P = .3574 and P = .1, respectively).

These findings could help guide physicians when discussing treatment and monitoring options with their patients, suggested study investigator Jan Šoupal, MD, PhD, of Charles University in Prague, when he presented the findings at the annual meeting of the European Association for the Study of Diabetes.

Dr. Šoupal and associates have previously reported data from the COMISAIR (Comparison of Different Treatment Modalities for Type 1 Diabetes Including Sensor-Augmented Insulin Regimens) study at 1 year of follow-up for 65 patients (Diabetes Technol Ther. 2016;18:532-8). The findings he presented at the EASD meeting, simultaneously published online in Diabetes Care, were for the full cohort of 94 patients and, with 3 years of follow-up, makes it “the longest CGM trial ever,” he said.

At the time the COMISAIR study was initiated, in 2013, “we knew that insulin pump therapy, especially in combination with real-time CGM, can improve several outcomes of patients with type 1 diabetes,” Dr. Šoupal observed. However, the effectiveness of CGM in patients with MDI was not widely described, and comparisons between continuous subcutaneous insulin infusion (CSII) and insulin MDI with rtCGM were lacking. “Moreover, we didn’t have any comparison between insulin pump therapy alone, without CGM, and MDI with CGM, and there were no long-term trials with real-time [continuous glucose monitoring].”

The aim of the COMISAIR study was therefore to compare four different treatment strategies in people with type 1 diabetes who had an HbA_1c of 7%-­­10% (53-86 mmol/mol), despite MDI treatment with insulin analogues and SMBG. The treatment strategies tested were CSII plus rtCGM (n = 26), MDI plus rtCGM (n = 22), CSII plus SMBG (n = 25), and MDI plus SMBG (n = 21). Patients were not randomized to these treatment arms but exposed to all of them during a 4-day DAFNE-like training session and then allowed to choose which they would like to use according to their individual needs and preferences, reflecting real-life practice.

Dr. Šoupal pointed out that two different continuous glucose monitoring devices had been used in the trial, and that 100% of the CGM groups wore a sensor for more than 70% of the time, which was one of the prerequisites for inclusion in the trial. Good adherence was observed, with 93% of patients completing all study visits, and CGM users wearing their sensors on average 88% of the time. “This nice adherence may be connected to the pretty good results,” he observed.

In discussing the HbA_1c results, Dr. Šoupal noted that “improvement observed in patients with [continuous glucose monitoring] is stable throughout 3 years, which is not always a reality for different types of treatment for diabetes.” In addition, “it is not so important how insulin is delivered, what is more important is how patients with type 1 diabetes monitor their glucose.”

Another key endpoint of the trial was time in range (70-180 mg/dL [3.9-10 mmol/L]). Results showed significantly more patients achieving this with rtCGM than with SMBG, regardless of whether they were using pump therapy or MDI. Comparing 3-year with baseline values, time in range was 72.3% versus 50.9% for rtCGM with CSII and 69% versus 48.7% for rtCGM with MDI (P less than .0001 for both). Results with SMBG with CSII or MDI were a respective 57.8% versus 50.6% (P = .0114) and 54.7% versus 51.8% (P = 1.0).

Glycemic variability was reduced in patients using insulin pumps with SBMG, and “not surprisingly, there was a reduction in both CGM-augmented groups,” Dr. Šoupal stated.

There was a reduction in the time spent in hypoglycemia from baseline to year 3 in all four groups, but that was significant only for the two rtCGM groups. Overall, there were seven severe hypoglycemia episodes, five in the SMBG groups (two in the CSII group, three in the MDI group) and two in the rtCGM groups (one each in the CSII and MDI groups), with one episode only occurring when the CGM sensor was not being worn.

Three episodes of ketoacidosis were reported – one each in the SMBG-pump, SMBG-MDI, and rtCGM-pump groups.

In summing up, Dr. Šoupal said that “real-time CGM, both with insulin pumps and with [multiple daily injections], provided significant, comparable, and stable improvement of glycemic outcomes.” He added that “treatment with CGM and MDI was more effective than treatment with insulin pump therapy alone, and that CGM and MDI can even be considered as a suitable alternative to treatment with insulin pumps and CMG for some patients.”

With many treatment options available, some will suit patients better than others, he suggested, but although “individualization of our treatment is important”, the COMISAIR data show that “it is CGM that makes the difference”.

The study was supported by the Agency for Healthcare Research and the Ministry of Health of the Czech Republic. Dr. Šoupal reported receiving honoraria from Abbott, AstraZeneca, Boehringer Ingelheim, Dexcom, Eli Lilly, Medtronic, Novo Nordisk, and Roche. Dexcom also paid for the development of the manuscript published in Diabetes Care.
 

SOURCES: Šoupal J et al. EASD 2019, Abstract 40; Šoupal J et al. Diabetes Care. 2019 Sep 17. doi: 10.2337/dc19-0888.

BARCELONA – Further differences in how adults and adolescents with type 2 diabetes respond to glucose and glucagon have been demonstrated by new data from the Restoring Insulin SEcretion (RISE) studies presented at the annual meeting of the European Association for the Study of Diabetes.

In a comparison of responses to an oral glucose tolerance test (OGTT), youth (n = 85) were more likely than were adults (n = 353) to have a biphasic type of glucose response curve (18.8% vs. 8.2%, respectively), which is considered a more normal response curve. However, that “did not foretell an advantageous outcome to the RISE interventions in the younger age group,” said study investigator Silva Arslanian, MD, of UPMC Children’s Hospital of Pittsburgh.

Fewer youth than adults had an incessant response (10.6% vs. 14.5%, respectively) or monophasic response to an OGTT (70.6% vs. 77.3%), and that was associated with lower beta-cell responses, compared with individuals with monophasic or biphasic glucose curves.

“Irrespective of curve type, insulin sensitivity was lower in youth than in adults,” Dr. Arslanian said. She added that beta-cell responses were greater in youth than in adults, except in youth with the worst incessant-increase curve type. In youth with the incessant-increase glucose curve, there was no evidence of beta-cell hypersecretion, which suggested youth “have more severe beta-cell dysfunction,” compared with adults.

There were also data presented on whether differences in alpha-cell function between youth and adults might be important. Those data showed that although fasting glucagon concentrations did not increase with fasting glucose in youth, they did in adults. It was found that fasting and stimulated glucagon concentrations were lower in youth than in adults, meaning that “alpha-cell function does not explain the beta-cell hyperresponsiveness seen in youth with impaired glucose tolerance or recently diagnosed type 2 diabetes,” reported study investigator Steven Kahn, MD, ChB, of VA Puget Sound Health Care System, University of Washington, Seattle.

M. Alexander Otto/MDedge News

“What was new, however, was that [the beta-cells of] youth were hyperresponsive and were really making large amounts of insulin.” Increased insulin production might be expected when there is insulin resistance, he added, but the level seen was “more than you would expect.” Over time, that might be toxic to the beta cells, and evidence from the earlier TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) studies suggested that the rate of beta-cell dysfunction was more rapid in youth than in adults.

Giving his perspective, as a pediatrician, on the new OGTT analyses from the RISE studies, Dr. Zeitler said that these data showed that the characteristic beta-cell hyperresponsiveness seen in youth “actually disappears as glycemia worsens.” In youth with the incessant glucose response pattern, “it shows that they cannot tolerate glucose, and their glucose levels just go up and up and up” until the beta cells fail.

This is a critical observation, Dr. Zeitler said, noting that it “sort of had to be the case, because sooner or later you had to lose beta cells ... this is probably the point where aggressive therapy is needed ... it was always a bit of a paradox, if these kids have such an aggressive course, how come they were starting out being so hyperresponsive?”

With regard to alpha-cell function, “these are really fresh data. We haven’t really had a long time to think about it,” said Dr. Zeitler. “What I find interesting is that there isn’t alpha-cell glucagon hypersecretion in youth like there is in adults.” That may be because youth are making so much insulin that they are suppressing glucagon production, but that’s not an entirely satisfying answer,” he said.

“The TODAY study demonstrated that diabetes in kids is aggressive; these RISE data now start to put some physiology around that, why is it more aggressive? Hyperresponsiveness, loss of beta-cell function over time, lack of response to intervention, compared with the adults.”

As for the clinical implications, Dr. Zeitler said that this is further evidence that the default approach to treating younger patients with greater caution than adults is perhaps not the best way to treat type 2 diabetes.

“These data are really showing that there is a very important toxic period that is occurring in these kids early on [and] that probably argues for more, not less, aggressive therapy,” than with adults. “Clearly, something is happening that is putting them at really big risk for rapid progression, and that’s your chance to treat much more aggressively, much earlier.”

The RISE studies are sponsored by the RISE Study Group in collaboration with the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Zeitler disclosed that he had acted as a consultant to Boehringer-Ingelheim, Eli Lilly, Daiichi-Sankyo and Merck, Sharp & Dohme, and had received research support from Janssen. Dr. Arslanian stated that she has nothing to disclose. Dr. Khan did not provide any disclosure information.

SOURCES: Arslanian S. EASD 2019, Oral presentation S34.1; Kahn S. EASD 2019, Oral presentation S34.3

BARCELONA – Further differences in how adults and adolescents with type 2 diabetes respond to glucose and glucagon have been demonstrated by new data from the Restoring Insulin SEcretion (RISE) studies presented at the annual meeting of the European Association for the Study of Diabetes.

In a comparison of responses to an oral glucose tolerance test (OGTT), youth (n = 85) were more likely than were adults (n = 353) to have a biphasic type of glucose response curve (18.8% vs. 8.2%, respectively), which is considered a more normal response curve. However, that “did not foretell an advantageous outcome to the RISE interventions in the younger age group,” said study investigator Silva Arslanian, MD, of UPMC Children’s Hospital of Pittsburgh.

Fewer youth than adults had an incessant response (10.6% vs. 14.5%, respectively) or monophasic response to an OGTT (70.6% vs. 77.3%), and that was associated with lower beta-cell responses, compared with individuals with monophasic or biphasic glucose curves.

“Irrespective of curve type, insulin sensitivity was lower in youth than in adults,” Dr. Arslanian said. She added that beta-cell responses were greater in youth than in adults, except in youth with the worst incessant-increase curve type. In youth with the incessant-increase glucose curve, there was no evidence of beta-cell hypersecretion, which suggested youth “have more severe beta-cell dysfunction,” compared with adults.

There were also data presented on whether differences in alpha-cell function between youth and adults might be important. Those data showed that although fasting glucagon concentrations did not increase with fasting glucose in youth, they did in adults. It was found that fasting and stimulated glucagon concentrations were lower in youth than in adults, meaning that “alpha-cell function does not explain the beta-cell hyperresponsiveness seen in youth with impaired glucose tolerance or recently diagnosed type 2 diabetes,” reported study investigator Steven Kahn, MD, ChB, of VA Puget Sound Health Care System, University of Washington, Seattle.

M. Alexander Otto/MDedge News

“What was new, however, was that [the beta-cells of] youth were hyperresponsive and were really making large amounts of insulin.” Increased insulin production might be expected when there is insulin resistance, he added, but the level seen was “more than you would expect.” Over time, that might be toxic to the beta cells, and evidence from the earlier TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) studies suggested that the rate of beta-cell dysfunction was more rapid in youth than in adults.

Giving his perspective, as a pediatrician, on the new OGTT analyses from the RISE studies, Dr. Zeitler said that these data showed that the characteristic beta-cell hyperresponsiveness seen in youth “actually disappears as glycemia worsens.” In youth with the incessant glucose response pattern, “it shows that they cannot tolerate glucose, and their glucose levels just go up and up and up” until the beta cells fail.

This is a critical observation, Dr. Zeitler said, noting that it “sort of had to be the case, because sooner or later you had to lose beta cells ... this is probably the point where aggressive therapy is needed ... it was always a bit of a paradox, if these kids have such an aggressive course, how come they were starting out being so hyperresponsive?”

With regard to alpha-cell function, “these are really fresh data. We haven’t really had a long time to think about it,” said Dr. Zeitler. “What I find interesting is that there isn’t alpha-cell glucagon hypersecretion in youth like there is in adults.” That may be because youth are making so much insulin that they are suppressing glucagon production, but that’s not an entirely satisfying answer,” he said.

“The TODAY study demonstrated that diabetes in kids is aggressive; these RISE data now start to put some physiology around that, why is it more aggressive? Hyperresponsiveness, loss of beta-cell function over time, lack of response to intervention, compared with the adults.”

As for the clinical implications, Dr. Zeitler said that this is further evidence that the default approach to treating younger patients with greater caution than adults is perhaps not the best way to treat type 2 diabetes.

“These data are really showing that there is a very important toxic period that is occurring in these kids early on [and] that probably argues for more, not less, aggressive therapy,” than with adults. “Clearly, something is happening that is putting them at really big risk for rapid progression, and that’s your chance to treat much more aggressively, much earlier.”

The RISE studies are sponsored by the RISE Study Group in collaboration with the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Zeitler disclosed that he had acted as a consultant to Boehringer-Ingelheim, Eli Lilly, Daiichi-Sankyo and Merck, Sharp & Dohme, and had received research support from Janssen. Dr. Arslanian stated that she has nothing to disclose. Dr. Khan did not provide any disclosure information.

SOURCES: Arslanian S. EASD 2019, Oral presentation S34.1; Kahn S. EASD 2019, Oral presentation S34.3

BARCELONA – Further differences in how adults and adolescents with type 2 diabetes respond to glucose and glucagon have been demonstrated by new data from the Restoring Insulin SEcretion (RISE) studies presented at the annual meeting of the European Association for the Study of Diabetes.

In a comparison of responses to an oral glucose tolerance test (OGTT), youth (n = 85) were more likely than were adults (n = 353) to have a biphasic type of glucose response curve (18.8% vs. 8.2%, respectively), which is considered a more normal response curve. However, that “did not foretell an advantageous outcome to the RISE interventions in the younger age group,” said study investigator Silva Arslanian, MD, of UPMC Children’s Hospital of Pittsburgh.

Fewer youth than adults had an incessant response (10.6% vs. 14.5%, respectively) or monophasic response to an OGTT (70.6% vs. 77.3%), and that was associated with lower beta-cell responses, compared with individuals with monophasic or biphasic glucose curves.

“Irrespective of curve type, insulin sensitivity was lower in youth than in adults,” Dr. Arslanian said. She added that beta-cell responses were greater in youth than in adults, except in youth with the worst incessant-increase curve type. In youth with the incessant-increase glucose curve, there was no evidence of beta-cell hypersecretion, which suggested youth “have more severe beta-cell dysfunction,” compared with adults.

There were also data presented on whether differences in alpha-cell function between youth and adults might be important. Those data showed that although fasting glucagon concentrations did not increase with fasting glucose in youth, they did in adults. It was found that fasting and stimulated glucagon concentrations were lower in youth than in adults, meaning that “alpha-cell function does not explain the beta-cell hyperresponsiveness seen in youth with impaired glucose tolerance or recently diagnosed type 2 diabetes,” reported study investigator Steven Kahn, MD, ChB, of VA Puget Sound Health Care System, University of Washington, Seattle.

M. Alexander Otto/MDedge News

“What was new, however, was that [the beta-cells of] youth were hyperresponsive and were really making large amounts of insulin.” Increased insulin production might be expected when there is insulin resistance, he added, but the level seen was “more than you would expect.” Over time, that might be toxic to the beta cells, and evidence from the earlier TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) studies suggested that the rate of beta-cell dysfunction was more rapid in youth than in adults.

Giving his perspective, as a pediatrician, on the new OGTT analyses from the RISE studies, Dr. Zeitler said that these data showed that the characteristic beta-cell hyperresponsiveness seen in youth “actually disappears as glycemia worsens.” In youth with the incessant glucose response pattern, “it shows that they cannot tolerate glucose, and their glucose levels just go up and up and up” until the beta cells fail.

This is a critical observation, Dr. Zeitler said, noting that it “sort of had to be the case, because sooner or later you had to lose beta cells ... this is probably the point where aggressive therapy is needed ... it was always a bit of a paradox, if these kids have such an aggressive course, how come they were starting out being so hyperresponsive?”

With regard to alpha-cell function, “these are really fresh data. We haven’t really had a long time to think about it,” said Dr. Zeitler. “What I find interesting is that there isn’t alpha-cell glucagon hypersecretion in youth like there is in adults.” That may be because youth are making so much insulin that they are suppressing glucagon production, but that’s not an entirely satisfying answer,” he said.

“The TODAY study demonstrated that diabetes in kids is aggressive; these RISE data now start to put some physiology around that, why is it more aggressive? Hyperresponsiveness, loss of beta-cell function over time, lack of response to intervention, compared with the adults.”

As for the clinical implications, Dr. Zeitler said that this is further evidence that the default approach to treating younger patients with greater caution than adults is perhaps not the best way to treat type 2 diabetes.

“These data are really showing that there is a very important toxic period that is occurring in these kids early on [and] that probably argues for more, not less, aggressive therapy,” than with adults. “Clearly, something is happening that is putting them at really big risk for rapid progression, and that’s your chance to treat much more aggressively, much earlier.”

The RISE studies are sponsored by the RISE Study Group in collaboration with the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Zeitler disclosed that he had acted as a consultant to Boehringer-Ingelheim, Eli Lilly, Daiichi-Sankyo and Merck, Sharp & Dohme, and had received research support from Janssen. Dr. Arslanian stated that she has nothing to disclose. Dr. Khan did not provide any disclosure information.

SOURCES: Arslanian S. EASD 2019, Oral presentation S34.1; Kahn S. EASD 2019, Oral presentation S34.3

BARCELONA – A similar overall risk of symptomatic hypoglycemia was observed with insulin degludec (Tresiba) and insulin glargine U300 (Toujeo) in the phase 3 CONCLUDE study data presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDedge News

During a 36-week maintenance treatment period, the rate ratio (RR) for the primary endpoint of the study – severe or confirmed symptomatic hypoglycemia, defined as a blood-glucose level of less than 3.1 mmol/L (56 mg/dL) – was 0.88 (95% confidence interval, 0.73-1.06; P = .17) in a comparison the two long-acting insulins.

There were some differences that favored insulin degludec over insulin glargine when other endpoints were considered, but because a statistical testing hierarchy was used, “no confirmatory results can be made from CONCLUDE,” one of the study investigators, Athena Philis-Tsimikas, MD, of Scripps Whittier Diabetes Institute, San Diego, said during a special symposium at the meeting.

“If the primary endpoint was not achieved, the testing hierarchy stopped after the first occurrence of nonsignificance,” she explained. Although that occurred, the other endpoints could still be analyzed as they were all prespecified, she argued. These showed that during the maintenance treatment period, there were lower rates of nocturnal symptomatic hypoglycemic episodes (RR, 0.63; 95% CI, 0.48-0.84; P = .0014) and severe episodes (those requiring third-party assistance; RR, 0.20; 95% CI, 0.07-0.57; P = .0027) with insulin degludec, compared with insulin glargine.

The trial came under fire, however, from Stefano Del Prato, MD, professor of endocrinology in the department of endocrinology metabolism and chief of the section of diabetes at the University of Pisa, Italy, who provided the EASD-invited independent commentary on the study’s findings. “This is the CONCLUDE trial. You’d could expect a CONCLUDE trial to be conclusive in its conclusions!” he said, noting that there were “too many uncertainties” in the trial.

CONCLUDE was a randomized, open-label, head-to-head study of insulin degludec versus insulin glargine in 1,609 adult patients with type 2 diabetes who were inadequately treated with basal insulin with or without oral antidiabetic drugs. The aim of the trial was to evaluate the risk of hypoglycemia associated with the two long-acting insulins.

“Hypoglycemia is a very common event in both type 1 and type 2 diabetes,” Thomas Pieber, MD, Medical University Graz, Austria, reminded the audience. Severe hypoglycemia is associated with insulin use, and data show that patients with type 2 diabetes are at as much risk as are those with type 1 diabetes in the longer term (Diabetologia. 2007;50:1140-7).

Sara Freeman/MDedge News

Sara Freeman/MDedge News

He said that it was not clear from the findings why there might be a lower risk of hypoglycemia with insulin degludec. He noted that the rate of diurnal hypoglycemia should be considered, and that the statistical interpretation of the data may be “a matter of uncertainty as well.”

Dr. Del Prato agreed that “prevention of hypoglycemia remained a major task in treating type 2 diabetic patients, particularly those on insulin therapy.” He proposed that differentiating between new basal insulin analogs may need “better tools for characterization of PK/PD, rigorous interpretation of the results, careful assessment of the generalizability of results from randomized controlled trials performed in selected study populations, and independent research and careful real-world studies to be performed.”

Furthermore, he said translating the potential benefit of new insulin analogs “cannot just rely on their properties, rather it requires validation over the time of the accuracy of glucose meters, and adequate patient education, and even more, education reinforcement.”

All of the speakers disclosed ties with Novo Nordisk, which funded the study, as well as other pharmaceutical companies.
 

SOURCES: Philis-Tsimikas A. EASD 2019, Oral Presentation 90; Pieber T. EASD 2019, Oral Presentation S38.1; Philis-Tsimikas A. EASD 2019, Oral Presentation S38.2; Del Prato S. EASD 2019. Oral Presentation S38.3.

BARCELONA – A similar overall risk of symptomatic hypoglycemia was observed with insulin degludec (Tresiba) and insulin glargine U300 (Toujeo) in the phase 3 CONCLUDE study data presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDedge News

During a 36-week maintenance treatment period, the rate ratio (RR) for the primary endpoint of the study – severe or confirmed symptomatic hypoglycemia, defined as a blood-glucose level of less than 3.1 mmol/L (56 mg/dL) – was 0.88 (95% confidence interval, 0.73-1.06; P = .17) in a comparison the two long-acting insulins.

There were some differences that favored insulin degludec over insulin glargine when other endpoints were considered, but because a statistical testing hierarchy was used, “no confirmatory results can be made from CONCLUDE,” one of the study investigators, Athena Philis-Tsimikas, MD, of Scripps Whittier Diabetes Institute, San Diego, said during a special symposium at the meeting.

“If the primary endpoint was not achieved, the testing hierarchy stopped after the first occurrence of nonsignificance,” she explained. Although that occurred, the other endpoints could still be analyzed as they were all prespecified, she argued. These showed that during the maintenance treatment period, there were lower rates of nocturnal symptomatic hypoglycemic episodes (RR, 0.63; 95% CI, 0.48-0.84; P = .0014) and severe episodes (those requiring third-party assistance; RR, 0.20; 95% CI, 0.07-0.57; P = .0027) with insulin degludec, compared with insulin glargine.

The trial came under fire, however, from Stefano Del Prato, MD, professor of endocrinology in the department of endocrinology metabolism and chief of the section of diabetes at the University of Pisa, Italy, who provided the EASD-invited independent commentary on the study’s findings. “This is the CONCLUDE trial. You’d could expect a CONCLUDE trial to be conclusive in its conclusions!” he said, noting that there were “too many uncertainties” in the trial.

CONCLUDE was a randomized, open-label, head-to-head study of insulin degludec versus insulin glargine in 1,609 adult patients with type 2 diabetes who were inadequately treated with basal insulin with or without oral antidiabetic drugs. The aim of the trial was to evaluate the risk of hypoglycemia associated with the two long-acting insulins.

“Hypoglycemia is a very common event in both type 1 and type 2 diabetes,” Thomas Pieber, MD, Medical University Graz, Austria, reminded the audience. Severe hypoglycemia is associated with insulin use, and data show that patients with type 2 diabetes are at as much risk as are those with type 1 diabetes in the longer term (Diabetologia. 2007;50:1140-7).

Sara Freeman/MDedge News

Sara Freeman/MDedge News

He said that it was not clear from the findings why there might be a lower risk of hypoglycemia with insulin degludec. He noted that the rate of diurnal hypoglycemia should be considered, and that the statistical interpretation of the data may be “a matter of uncertainty as well.”

Dr. Del Prato agreed that “prevention of hypoglycemia remained a major task in treating type 2 diabetic patients, particularly those on insulin therapy.” He proposed that differentiating between new basal insulin analogs may need “better tools for characterization of PK/PD, rigorous interpretation of the results, careful assessment of the generalizability of results from randomized controlled trials performed in selected study populations, and independent research and careful real-world studies to be performed.”

Furthermore, he said translating the potential benefit of new insulin analogs “cannot just rely on their properties, rather it requires validation over the time of the accuracy of glucose meters, and adequate patient education, and even more, education reinforcement.”

All of the speakers disclosed ties with Novo Nordisk, which funded the study, as well as other pharmaceutical companies.
 

SOURCES: Philis-Tsimikas A. EASD 2019, Oral Presentation 90; Pieber T. EASD 2019, Oral Presentation S38.1; Philis-Tsimikas A. EASD 2019, Oral Presentation S38.2; Del Prato S. EASD 2019. Oral Presentation S38.3.

BARCELONA – A similar overall risk of symptomatic hypoglycemia was observed with insulin degludec (Tresiba) and insulin glargine U300 (Toujeo) in the phase 3 CONCLUDE study data presented at the annual meeting of the European Association for the Study of Diabetes.

Sara Freeman/MDedge News

During a 36-week maintenance treatment period, the rate ratio (RR) for the primary endpoint of the study – severe or confirmed symptomatic hypoglycemia, defined as a blood-glucose level of less than 3.1 mmol/L (56 mg/dL) – was 0.88 (95% confidence interval, 0.73-1.06; P = .17) in a comparison the two long-acting insulins.

There were some differences that favored insulin degludec over insulin glargine when other endpoints were considered, but because a statistical testing hierarchy was used, “no confirmatory results can be made from CONCLUDE,” one of the study investigators, Athena Philis-Tsimikas, MD, of Scripps Whittier Diabetes Institute, San Diego, said during a special symposium at the meeting.

“If the primary endpoint was not achieved, the testing hierarchy stopped after the first occurrence of nonsignificance,” she explained. Although that occurred, the other endpoints could still be analyzed as they were all prespecified, she argued. These showed that during the maintenance treatment period, there were lower rates of nocturnal symptomatic hypoglycemic episodes (RR, 0.63; 95% CI, 0.48-0.84; P = .0014) and severe episodes (those requiring third-party assistance; RR, 0.20; 95% CI, 0.07-0.57; P = .0027) with insulin degludec, compared with insulin glargine.

The trial came under fire, however, from Stefano Del Prato, MD, professor of endocrinology in the department of endocrinology metabolism and chief of the section of diabetes at the University of Pisa, Italy, who provided the EASD-invited independent commentary on the study’s findings. “This is the CONCLUDE trial. You’d could expect a CONCLUDE trial to be conclusive in its conclusions!” he said, noting that there were “too many uncertainties” in the trial.

CONCLUDE was a randomized, open-label, head-to-head study of insulin degludec versus insulin glargine in 1,609 adult patients with type 2 diabetes who were inadequately treated with basal insulin with or without oral antidiabetic drugs. The aim of the trial was to evaluate the risk of hypoglycemia associated with the two long-acting insulins.

“Hypoglycemia is a very common event in both type 1 and type 2 diabetes,” Thomas Pieber, MD, Medical University Graz, Austria, reminded the audience. Severe hypoglycemia is associated with insulin use, and data show that patients with type 2 diabetes are at as much risk as are those with type 1 diabetes in the longer term (Diabetologia. 2007;50:1140-7).

Sara Freeman/MDedge News

Sara Freeman/MDedge News

He said that it was not clear from the findings why there might be a lower risk of hypoglycemia with insulin degludec. He noted that the rate of diurnal hypoglycemia should be considered, and that the statistical interpretation of the data may be “a matter of uncertainty as well.”

Dr. Del Prato agreed that “prevention of hypoglycemia remained a major task in treating type 2 diabetic patients, particularly those on insulin therapy.” He proposed that differentiating between new basal insulin analogs may need “better tools for characterization of PK/PD, rigorous interpretation of the results, careful assessment of the generalizability of results from randomized controlled trials performed in selected study populations, and independent research and careful real-world studies to be performed.”

Furthermore, he said translating the potential benefit of new insulin analogs “cannot just rely on their properties, rather it requires validation over the time of the accuracy of glucose meters, and adequate patient education, and even more, education reinforcement.”

All of the speakers disclosed ties with Novo Nordisk, which funded the study, as well as other pharmaceutical companies.
 

SOURCES: Philis-Tsimikas A. EASD 2019, Oral Presentation 90; Pieber T. EASD 2019, Oral Presentation S38.1; Philis-Tsimikas A. EASD 2019, Oral Presentation S38.2; Del Prato S. EASD 2019. Oral Presentation S38.3.