Occurrence of Gastrointestinal Adverse Events Upon GLP-1 Receptor Agonist Initiation With Concomitant Metformin Use: A Post Hoc Analysis of LEADER, STEP 2, SUSTAIN-6, and PIONEER 6
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OBJECTIVE: To assess the impact of concomitant metformin use on gastrointestinal adverse events during the initiation and titration of a glucagon-like peptide 1 receptor agonist (GLP-1RA). RESEARCH DESIGN AND METHODS: Using data from four clinical trials of liraglutide and semaglutide (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER], Semaglutide Treatment Effect in People with Obesity [STEP 2], Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6], and Peptide Innovation for Early Diabetes Treatment [PIONEER] 6), we compared the incidence of gastrointestinal adverse events during GLP-1RA initiation and titration in participants with and without concomitant metformin use. RESULTS: Of 16,996 participants, 12,928 (76%) were treated with metformin. Concomitant metformin use did not increase the percentage of participants who developed gastrointestinal adverse events or their severity during the observation window. Among participants experiencing gastrointestinal adverse events, metformin use did not increase study product discontinuation. Within treatment arms (GLP-1RA and placebo), a numerically higher percentage of metformin nonusers experienced gastrointestinal adverse events and discontinued the study product compared with metformin users. CONCLUSIONS: Concomitant metformin use does not increase occurrence of gastrointestinal symptoms during GLP-1RA initiation or impact GLP-1RA discontinuation.
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Combining GLP-1s with metformin does not appear to worsen gastrointestinal side effects.
“Combining GLP‐1s with metformin does not appear to worsen GI side effects, despite metformin's association with similar symptoms [50].”
Combining GLP-1s with metformin does not appear to worsen GI side effects.
“Combining GLP-1s with metformin does not appear to worsen GI side effects, despite metformin's association with similar symptoms [48].”
Combining GLP-1s with metformin does not appear to worsen GI side effects, despite metformin's association with similar symptoms.
“Combining GLP-1s with metformin does not appear to worsen GI side effects, despite metformin’s association with similar symptoms [50].”
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“Combining GLP-1s with metformin does not appear to worsen GI side effects, despite metformin ’ s association with similar symptoms [48].”
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- Authors
- Klein, K. R., Clemmensen, K. K. B., Fong, E., Olsen, S., Abrahamsen, T., & Lingvay, I.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Novo Nordisk (Denmark) (DK)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Klein, Klara R.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2023-12-04
- Volume
- 47
- Issue
- 2
- Pages
- 280-284
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC10834386
- OpenAlex
- W4389297608
- Cited by
- 22
- References
- 15
- Citations by year
- 2026: 3 · 2025: 16 · 2024: 3
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- Innovationsfonden
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK127984)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- gastrointestinal adverse effects, GLP-1 receptor agonists, metformin, liraglutide, semaglutide, type 2 diabetes, obesity, treatment discontinuation, drug-drug interactions
- MeSH terms
- Liraglutide, Glucagon-Like Peptide-1 Receptor Agonists, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Humans, Hypoglycemic Agents, Metformin
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