Semaglutide improves postprandial glucose and lipid metabolism, and delays first‐hour gastric emptying in subjects with obesity

Aim: To investigate the effects of semaglutide on fasting and postprandial glucose and lipid responses, and on gastric emptying. Materials and Methods: This was a randomised, double-blind, placebo-controlled, two-period, crossover trial. Subjects with obesity (N = 30) received once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, or placebo. After each 12-week treatment period, glucose and lipid metabolism were assessed before and after standardised meals. Gastric emptying (paracetamol absorption test) and peptide YY (PYY) response were also assessed. Results: Semaglutide treatment significantly lowered fasting concentrations of glucose and glucagon, and increased insulin versus placebo (estimated treatment ratio: 0.95 [95% confidence interval: 0.91, 0.98]; 0.86 [0.75, 0.98]; 1.45 [1.20, 1.75], respectively). Postprandial glucose metabolism significantly improved with semaglutide versus placebo (incremental area under the curve 0–5 hours [iAUC0-5h]; estimated treatment difference: glucose −1.34 mmol*h/L [−2.42, −0.27]; insulin −921 pmol*h/L [−1461, −381]; C-peptide −1.42 nmol*h/L [−2.33, −0.51]). Fasting and postprandial lipid metabolism improved with semaglutide versus placebo. First-hour gastric emptying after the meal was delayed versus placebo (AUC0-1h; estimated treatment ratio: 0.73 [0.61, 0.87]); this may have contributed to the lower postprandial glucose increase in semaglutide-treated subjects. Overall gastric emptying (AUC0-5h) was not statistically different between treatments. Fasting and postprandial PYY responses were significantly lower with semaglutide versus placebo (p=0.0397 and p=0.0097, respectively). Conclusion: Semaglutide improved fasting and postprandial glucose and lipid metabolism. Overall gastric emptying was similar to placebo; however, the observed first-hour delay with semaglutide may contribute to a slower entry of glucose into the circulation.