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Clinical Trial
. 2018 Mar;20(3):610-619.
doi: 10.1111/dom.13120. Epub 2017 Oct 27.

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

Julie B Hjerpsted  1 , Anne Flint  1 , Ashley Brooks  2 , Mads B Axelsen  1 , Trine Kvist  1 , John Blundell  3
Affiliations
Clinical Trial

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

Julie B Hjerpsted et al. Diabetes Obes Metab. 2018 Mar.

Abstract

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 [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).

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.

Keywords: GLP-1 analogue; glucose metabolism; incretin therapy; insulin analogues; obesity therapy; phase I-II study.

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Conflict of interest statement

M. B. A., A. F., J. B. H. and T. K. are full‐time employees of, and hold shares in, Novo Nordisk A/S. A. B. has received research grants from Novo Nordisk. J. B. has received research, travel and accommodation grants within the submitted work from Novo Nordisk A/S, and advisory and speaker fees outside the submitted work from Novo Nordisk A/S.

Figures

Figure 1
Figure 1
Mean glucose metabolism profiles after standardized, carbohydrate‐rich breakfast. Error bars represent standard error
Figure 2
Figure 2
Mean lipid metabolism profiles after standardized, fat‐rich breakfast. Error bars represent standard error. Abbreviation: VLDL, very‐low‐density lipoprotein
Figure 3
Figure 3
Gastric emptying: A, mean paracetamol profiles following standardized, carbohydrate‐rich breakfast. B, Mean PYY profile following standardized, carbohydrate‐rich breakfast. Error bars represent standard error. Abbreviation: PYY, peptide YY
See this image and copyright information in PMC

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