Incretin mimetics and acute pancreatitis: enemy or innocent bystander?

PURPOSE OF REVIEW: The incretin enhancers and mimetics, including dipeptidyl peptidase-4 (DPP-4) inhibitors, GLP-1 receptor agonists (GLP-1RA) and GLP-1/GIP co-agonists, have become mainstays in the treatment of type 2 diabetes (T2D). Recently, the approval of certain GLP-1RA and GLP-1/GIP co-agonists for the treatment of obesity has broadened their popularity and use. In this review, we summarize the evidence for an association of these drugs with acute pancreatitis and other adverse events of special interest to gastroenterologists. RECENT FINDINGS: In addition to pancreatic islets, GLP-1 receptors are expressed in the exocrine cells of the pancreas. There is inconsistent evidence for an association of DPP-4 inhibitors, GLP-1RA and co-agonists with risk for acute pancreatitis in individual trials. Meta-analyses of long-term randomized controlled trials indicate a small risk of acute pancreatitis associated with DPP-4 inhibitors but not GLP-1RA or co-agonists. Cholecystitis and cholelithiasis may be more common among those treated with GLP-1RA and GLP-1/GIP co-agonists. There is no evidence that any of these drugs are associated with an increased risk of pancreatic cancer. SUMMARY: While drugs that leverage the incretin system are increasingly being used for patients with T2D and obesity, caution in warranted in those with a history of pancreatitis and gallbladder disease.

Impaired Awareness of Hypoglycemia in Older Adults With Type 1 Diabetes: A Post Hoc Analysis of the WISDM Study.

OBJECTIVE: Up to one-third of older adults with type 1 diabetes experience impaired awareness of hypoglycemia (IAH), yet the factors associated with IAH remain underexplored in older adults. RESEARCH DESIGN AND METHODS: This post hoc analysis evaluated the clinical and glycemic correlates of IAH in adults ≥60 years old with type 1 diabetes in the WISDM study. IAH and normal awareness of hypoglycemia (NAH) were defined by a Clarke score of ≥4 or <4, respectively. Demographic, clinical, and glycemic metrics were compared in those with IAH and NAH at baseline and in whom IAH did or did not improve over 26 weeks, using descriptive statistics and a multiple logistic regression variable selection procedure. RESULTS: Of the 199 participants (age 68.1 ± 5.7 years, 52% female), 30.6% had IAH. At baseline, participants with IAH had a longer diabetes duration and greater daytime hypoglycemia and glycemic variability, and more participants had nondetectable C-peptide levels than those with NAH. Logistic regression associated longer diabetes duration (odds ratio [OR] 1.03, 95% CI 1.01-1.05; P = 0.008) and greater daytime hypoglycemia (OR 1.31, 95% CI, 1.15-1.51; P < 0.0001) with a greater odds of IAH. A similar modeling procedure identified less daytime hypoglycemia (OR per additional percentage point 0.55, 95% CI 0.32-0.94; P = 0.029) and shorter diabetes duration (OR per additional year 0.96, 95% CI 0.91-1.004; P = 0.07) as predictors of restored awareness at 26 weeks, although the effect size for diabetes duration was not statistically significant. CONCLUSIONS: In older adults with type 1 diabetes, longer diabetes duration and greater daytime hypoglycemia are drivers of IAH. Dedicated research can personalize IAH management.

24-h energy expenditure in people with type 1 diabetes: impact on equations for clinical estimation of energy expenditure.

BACKGROUND/OBJECTIVES: Type 1 diabetes (T1D) is associated with an increase in resting metabolic rate (RMR), but the impact of T1D on other components of 24-h energy expenditure (24-h EE) is not known. Also, there is a lack of equations to estimate 24-h EE in patients with T1D. The aims of this analysis were to compare 24-h EE and its components in young adults with T1D and healthy controls across the spectrum of body mass index (BMI) and derive T1D-specific equations from clinical variables. SUBJECTS/METHODS: Thirty-three young adults with T1D diagnosed ≥1 year prior and 33 healthy controls matched for sex, age and BMI were included in this analysis. We measured 24-h EE inside a whole room indirect calorimeter (WRIC) and body composition with dual x-ray absorptiometry. RESULTS: Participants with T1D had significantly higher 24-h EE than healthy controls (T1D = 2047 ± 23 kcal/day vs control= 1908 ± 23 kcal/day; P < 0.01). We derived equations to estimate 24-h EE with both body composition (fat free mass + fat mass) and anthropometric (weight + height) models, which provided high coefficients of determination (R2 = 0.912 for both). A clinical model that did not incorporate spontaneous physical activity yielded high coefficients of determination as well (R2 = 0.897 and R2 = 0.880 for body composition and anthropometric models, respectively). CONCLUSION: These results confirm that young adults with established T1D have increased 24-h EE relative to controls without T1D. The derived equations from clinically available variables can assist clinicians with energy prescriptions for weight management in patients with T1D.