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

Abstract

AimTo investigate the effects of semaglutide on fasting and postprandial glucose and lipid responses, and on gastric emptying.Materials and methodsThis 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.ResultsSemaglutide 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 [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 vs placebo. First‐hour gastric emptying after the meal was delayed with semaglutide vs 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 vs placebo (P = .0397 and P = .0097, respectively).ConclusionSemaglutide 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.

Semaglutide as a promising antiobesity drug

“…GLP‐1RAs were shown to improve CV risk factors, including serum glucose levels, body weight, and blood pressure . Notably, semaglutide, liraglutide, and exenatide were found to improve postprandial lipemia, which has been linked to increased CV risk …”

A szemaglutid szerkezete és farmakológiája

“…A csoport más képviselőivel egyezően glukózfüggő módon serkenti az inzulinelválasztást és gátolja a glukagon release-t. A szemaglutid enyhén lassítja a korai postprandialis gyomorürülést, ezáltal lassítva azt a sebességet, amellyel a glukóz postprandialisan megjelenik a keringésben. 12 Erőteljesen mérsékli az éhomi vércukorszintet és a napszakos glykaemiát is. Mind anyagcserejavító, mind súlyleadást elősegítő hatása a legerőteljesebb a jelenleg forgalomban lévő származékok között.…”

The role of glucagon in the possible mechanism of cardiovascular mortality reduction in type 2 diabetes patients

“…On the contrary, chronic treatment with liraglutide does not seem to affect fasting glucagon concentrations and even more, causes upregulation of PP glucagon secretion (Table ) . Interestingly, the results regarding the effect of other drugs of the GLP‐1 analogue class (eg, semaglutide) on fasting glucagon are contradictory . Currently, there is no clear evidence that semaglutide and canagliglozin upregulate the PP glucagon levels during chronic treatment, however, this issue has not been sufficiently investigated yet.…”

“…Interestingly, the results regarding the effect of other drugs of the GLP‐1 analogue class (eg, semaglutide) on fasting glucagon are contradictory . Currently, there is no clear evidence that semaglutide and canagliglozin upregulate the PP glucagon levels during chronic treatment, however, this issue has not been sufficiently investigated yet. Therefore, while we are awaiting for the body of evidence to increase, it is possible that chronic upregulation of PP glucagon concentrations may be a unique characteristic of novel antidiabetic drugs with beneficial effect regarding mortality (empagliflozin, liraglutide).…”