Oral semaglutide improves postprandial glucose and lipid metabolism, and delays gastric emptying, in subjects with type 2 diabetes.
Level 2 - randomized trial
Randomized, double-blind, placebo-controlled crossover trial
PubMed 33710717 · doi:10.1111/dom.14373
What was done
In a randomized, double-blind, single-centre crossover trial, 15 participants with type 2 diabetes received once-daily oral semaglutide (dose escalated to 14 mg) followed by placebo, or vice versa, over two consecutive 12-week periods. At the end of each treatment period, glucose and lipid metabolism and gastric emptying (measured via paracetamol absorption) were evaluated before and after standardized meals (standard and fat-rich). The primary endpoint was the postprandial glucose area under the curve (AUC 0-5h) after a standard breakfast.
What was found
Oral semaglutide significantly reduced postprandial glucose AUC 0-5h compared with placebo (estimated treatment ratio 0.71; 95% CI, 0.63 to 0.81; p < .0001), with corresponding reductions in glucose incremental AUC (iAUC 0-5h/5h) and glucagon AUC 0-5h (similar reductions occurred after the fat-rich breakfast). Fasting glucose was lower and fasting C-peptide was higher on semaglutide. For lipid metabolism, fasting concentrations and AUC 0-8h of triglycerides, VLDL, and ApoB48, as well as triglyceride iAUC 0-8h/8h, were all significantly reduced with semaglutide versus placebo. Gastric emptying during the first postprandial hour was delayed, marked by a 31% reduction in paracetamol AUC 0-1h. One serious adverse event (acute myocardial infarction) occurred during semaglutide treatment.
Why it matters
This study shows that oral semaglutide improves both postprandial glucose and lipid control in type 2 diabetes, driven in part by delayed early gastric emptying and suppressed postprandial glucagon secretion.
Limits
The study had a very small sample size (n = 15) and was conducted at a single centre. The cohort was predominantly male (86.7%) with relatively well-controlled baseline diabetes (mean HbA1c 6.9%), limiting generalizability to broader patient populations with worse glycemic control. Long-term clinical cardiovascular outcomes and sustained gastric emptying effects could not be determined.
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