Oral semaglutide improves postprandial glucose and lipid metabolism, and delays gastric emptying, in subjects with type 2 diabetes

Aim: To assess the effects of oral semaglutide on postprandial glucose and lipid metabolism, and gastric emptying, in subjects with type 2 diabetes (T2D). Materials and Methods: In this randomized, double-blind, single-centre, crossover trial, subjects with T2D received once-daily oral semaglutide (escalated to 14 mg) followed by placebo, or vice versa, over two consecutive 12-week periods. Glucose and lipid metabolism, and gastric emptying (paracetamol absorption) were assessed before and after two types of standardized meals (standard and/or fat-rich) at the end of each treatment period. The primary endpoint was area under the glucose 0-5-h curve (AUC(0-5h)) after the standard breakfast. Results: Fifteen subjects were enrolled (mean age 58.2 years, HbA1c 6.9%, body weight 93.9 kg, diabetes duration 3.1 years; 13 [86.7%] males). Fasting concentrations of glucose were significantly lower, and C-peptide significantly greater, with oral semaglutide versus placebo. Postprandial glucose (AUC(0-5h)) was significantly lower with oral semaglutide versus placebo (estimated treatment ratio, 0.71; 95% CI, 0.63, 0.81; p < .0001); glucose incremental AUC (iAUC(0-5h/5h)) and glucagon AUC(0-5h) were also significantly reduced, with similar results after the fat-rich breakfast. Fasting concentrations of triglycerides, very low-density lipoprotein (VLDL) and apolipoprotein B48 (ApoB48) were significantly lower with oral semaglutide versus placebo. AUC(0-8h) for triglycerides, VLDL and ApoB48, and triglycerides iAUC(0-8h/8h), were significantly reduced after oral semaglutide versus placebo. During the first postprandial hour, gastric emptying was delayed (a 31% decrease in paracetamol AUC(0-1h)) with oral semaglutide versus placebo. One serious adverse event (acute myocardial infarction) occurred during oral semaglutide treatment. Conclusion: Oral semaglutide significantly improved fasting and postprandial glucose and lipid metabolism, and delayed gastric emptying.

Automated summary

Oral semaglutide significantly improved both fasting and postprandial glucose and lipid metabolism, and delayed gastric emptying in subjects with type 2 diabetes. However, one serious adverse event (acute myocardial infarction) did occur during the treatment.