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

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Dahl, Kirsten, Brooks, Ashley, Almazedi, Firas, Hoff, Søren Tetens, Boschini, Cristina, Bækdal, Tine A.·2021·Diabetes, Obesity and Metabolism
DOI 10.1111/dom.14373PMC PMC8251575
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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 (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.

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  • In patients with type 2 diabetes after 12 weeks of oral semaglutide treatment, gastric emptying was significantly delayed during the first postprandial hour compared with control (p = 0.005), but no difference was observed after five hours.

    “Dahl et al. [34] observed a significant delay in gastric emptying during the first postprandial hour in the semaglutide group (p = 0.005), but no difference after five hours.”

    From Delayed gastric emptying induced by glucagon-like peptide-1 receptor agonists and its implications for perioperative risk during anesthesia (2026) · cites this paper as [34]

    The Results (Gastric emptying) report 31% lower first-hour paracetamol absorption with oral semaglutide than placebo (p = .0050), supporting the reported delay. They say absorption was not significantly different over the five-hour period, not that there was no difference after five hours. The Materials and Methods describe the two 12-week treatment periods in subjects with type 2 diabetes. (LLM, conf=0.86)

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Authors
Dahl, K., Brooks, A., Almazedi, F., Hoff, S. T., Boschini, C., & Bækdal, T. A.
Affiliations
  • Novo Nordisk (Denmark) (DK)
  • Covance (United Kingdom) (GB)
  • Novo Nordisk A/S Søborg Denmark
Corresponding author
Dahl, Kirsten
ORCID
Venue
Diabetes, Obesity and Metabolism
Publisher
Wiley
Published
2021-03-29
Volume
23
Issue
7
Pages
1594-1603
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
DOI
10.1111/dom.14373
PMC
PMC8251575
OpenAlex
W3135617910
Cited by
87
References
8
Citations by year
2026: 15 · 2025: 17 · 2024: 23 · 2023: 14 · 2022: 11 · 2021: 6
FWCI
10.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
oral semaglutide, type 2 diabetes, postprandial blood glucose, lipid metabolism, triglycerides, VLDL, apolipoprotein B-48, gastric emptying, paracetamol absorption, glucagon, C-peptide, GLP-1 receptor agonists, high-fat meal, acute myocardial infarction, adverse events, glycemic control
MeSH terms
Semaglutide, Blood Glucose, Diabetes Mellitus, Type 2, Double-Blind Method, Glucagon-Like Peptides, Gastric Emptying, Glucose, Humans, Hypoglycemic Agents, Male, Middle Aged, Postprandial Period, Lipid Metabolism

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