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Randomized Controlled Trial
. 2021 Jul;23(7):1594-1603.
doi: 10.1111/dom.14373. Epub 2021 Mar 29.

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

Kirsten Dahl  1 , Ashley Brooks  2 , Firas Almazedi  2 , Søren Tetens Hoff  1 , Cristina Boschini  1 , Tine A Baekdal  1
Affiliations
Randomized Controlled Trial

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

Kirsten Dahl et al. Diabetes Obes Metab. 2021 Jul.

Abstract

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 (AUC0-5h ) 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 (AUC0-5h ) was significantly lower with oral semaglutide versus placebo (estimated treatment ratio, 0.71; 95% CI, 0.63, 0.81; p < .0001); glucose incremental AUC (iAUC0-5h/5h ) and glucagon AUC0-5h 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. AUC0-8h for triglycerides, VLDL and ApoB48, and triglycerides iAUC0-8h/8h , were significantly reduced after oral semaglutide versus placebo. During the first postprandial hour, gastric emptying was delayed (a 31% decrease in paracetamol AUC0-1h ) 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.

Keywords: GLP-1 analogue; dyslipidaemia; glycaemic control; incretin therapy; pharmacodynamics; type 2 diabetes.

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Conflict of interest statement

KD, STH, CB and TAB are employees, and KD, STH and TAB shareholders, of Novo Nordisk A/S, the sponsor of this trial. FA and AB are employees of Covance Clinical Research Unit Ltd, the site where the trial was conducted; they did not receive any direct funding, nor have financial affiliations with the trial sponsor.

Figures

FIGURE 1
FIGURE 1
Trial design
FIGURE 2
FIGURE 2
Mean postprandial glucose metabolism profiles after A, a standard breakfast; and B, a fat‐rich breakfast. Data are observed means. p‐values are for the ETR for fasting concentrations and AUC, and the ETD for iAUC, for oral semaglutide versus placebo. *p < .05; **p < .01; ***p < .001. †Difference was not statistically significant. AUC, area under the concentration–time curve; ETD, estimated treatment difference; ETR, estimated treatment ratio; iAUC, incremental area under the concentration–time curve
FIGURE 3
FIGURE 3
Mean postprandial lipid metabolism profiles after a fat‐rich breakfast. Data are observed means. p‐values are for the ETR for fasting concentrations and AUC, and the ETD for iAUC, for oral semaglutide versus placebo. *p < .05; **p < .01; ***p < .001. †Difference was not statistically significant. ApoB48, apolipoprotein B48; AUC, area under the concentration–time curve; ETD, estimated treatment difference; ETR, estimated treatment ratio; FFA, free fatty acids; iAUC, incremental area under the concentration–time curve; VLDL, very low‐density lipoprotein
FIGURE 4
FIGURE 4
Mean paracetamol profile after a standard lunch. Data are observed means. p‐values are for the ETR for oral semaglutide versus placebo. ***p < .001. †Difference was not statistically significant. AUC, area under the concentration–time curve; ETR, estimated treatment ratio
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