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.

RESEARCH DESIGN AND 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 randomised to training were evaluated before and after training. The primary outcome was a change in insulin secretory capacity with training, evaluated by a two-stepped hyperglycemic (20 and 30-millimolar) clamp.

RESULTS: Training increased the incremental area under the curve for insulin from 21 to 27 nanomolar • 2h (ratio 1.28 (95% confidence interval [CI] 1.02-1.60) during clamp step 1 and from 40 to 64 nanomolar • 2h (ratio 1.61, 95% CI 1.25-2.07) during step 2. Semaglutide treatment increased insulin secretion from 16 to 111 nanomolar • 2h (ratio 7.10, 95% CI 3.68-13.71), and from 35 to 447 nanomolar • 2h (ratio 12.74, 95% CI, 5.65-28.71), correspondingly. Semaglutide and training increased insulin secretion from 130 to 171 nanomolar • 2h (ratio 1.31, 95% CI 1.06-1.63), and from 525 to 697 nanomolar • 2h (ratio 1.33, 95% CI 1.02-1.72), correspondingly. The median increase in total insulin secretion with the combination was 134 nanomolar • 2h greater (95% CI 108-232) than with training.

CONCLUSIONS: The combination of aerobic training and semaglutide treatment synergistically improved β-cell secretory function. (ClinicalTrials.gov number, ID NCT04383197).