Effects of Aerobic Training and Semaglutide Treatment on Pancreatic β-Cell Secretory Function in Patients With Type 2 Diabetes

Abstract Context Prior to this study, it is known that type 2 diabetes is linked to obesity and a sedentary lifestyle, leading to inadequate β-cell function and insulin resistance. Limited research has explored the metabolic effects of combining exercise training with antidiabetic medications, particularly focusing on insulin secretion in patients with type 2 diabetes and moderately preserved β-cell function. Objective The effect of the interaction of semaglutide and physical training on pancreatic β-cell secretory function is unknown in patients with type 2 diabetes. Methods Thirty-one patients with type 2 diabetes underwent 12 weeks of aerobic training alone or concurrent to treatment with semaglutide. Patients randomly allocated to concurrent semaglutide and training were treated with semaglutide for 20 weeks before the training and evaluated at inclusion and again before and after the training intervention. Patients randomized to training were evaluated before and after training. The primary outcome was a change in insulin secretory capacity with training, evaluated by a 2-stepped hyperglycemic (20 and 30 mM) clamp. Results Training increased the incremental area under the curve for insulin from 21 to 27 nM × 2 hours (ratio 1.28, 95% CI 1.02-1.60) during clamp step 1 and from 40 to 64 nM × 2 hours (ratio 1.61, 95% CI 1.25-2.07) during step 2. Semaglutide treatment increased insulin secretion from 16 to 111 nM × 2 hours (ratio 7.10, 95% CI 3.68-13.71), and from 35 to 447 nM × 2 hours (ratio 12.74, 95% CI 5.65-28.71), correspondingly. Semaglutide and training increased insulin secretion from 130 to 171 nM × 2 hours (ratio 1.31, 95% CI 1.06-1.63), and from 525 to 697 nM × 2 hours (ratio 1.33, 95% CI 1.02-1.72), correspondingly. The median increase in total insulin secretion with the combination was 134 nM × 2 hours greater (95% CI 108-232) than with training. Conclusion The combination of aerobic training and semaglutide treatment synergistically improved β-cell secretory function. (ClinicalTrials.gov number, ID NCT04383197).