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 randomized, double‐blind, placebo‐controlled, 2‐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 standardized 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 vs 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 vs placebo (incremental area under the curve 0 to 5 hours [iAUC(0‐5h)]; 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 vs placebo. First‐hour gastric emptying after the meal was delayed with semaglutide vs placebo (AUC(0‐1h); 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 (AUC(0‐5h)) was not statistically different between treatments. Fasting and postprandial PYY responses were significantly lower with semaglutide vs placebo (P = .0397 and P = .0097, respectively). CONCLUSION: Semaglutide improved fasting and postprandial glucose and lipid metabolism. Overall gastric emptying was similar to that with placebo; however, the observed first‐hour delay with semaglutide may contribute to a slower entry of glucose into the circulation.