Type 2 diabetes: gastrointestinal side effects vary depending on GLP-1 agonist

Semaglutide caused the highest rates of GI symptoms, while liraglutide was associated with more pain in the upper abdomen.

Findings

• In adverse event reports (UEs) in the U.S., glucagon-like peptide-1 receptor agonists (GLP-1RAs) were significantly associated with gastrointestinal (GI)  UEs.
• Semaglutide was associated with the greatest risk of nausea, diarrhea, vomiting, constipation and pancreatitis, while liraglutide was more strongly associated with epigastric pain.

Why this matters

• GLP-1RAs are increasingly recommended for the treatment of type 2 diabetes due to their beneficial effects on glycemic control and reduction of cardiovascular risks.
• The GI-UEs occurring with GLP-1RAs are due to the activation of central and peripheral GLP-1 receptors.
• Differences in GI toxicity between different GLP-1RAs are not sufficiently known.

Study design

• Between January 2018 and June 2022, data from the U.S. FDA  Adverse Event Reporting System (FAERS).
• A total of 231,730-_ GLP-1RA-associated  UEs captured, including 21,281  GI-UEs.
• Funding: National Natural Science Foundation of China

Key results

• Compared to background frequency, reporting odds ratios (RORs) for diseases of the GI system were 1.46 for GLP-1RAs overall and 2.39, 1.39 and 3.00 for liraglutide, dulaglutide and semaglutide.
• No excessive GI-UEs have been reported for exenatide (ROR: 0.57) or lixisenatide (ROR: 0.51).
• The 6 most commonly reported GI-AEs were nausea (42,23 %), diarrhea (21.93 %), vomiting (21.90 %), upper abdominal pain (9.78 %), constipation (8.41 %) and pancreatitis (8.23 %).
• Semaglutide showed the greatest risk of nausea (ROR: 7.41; 95 % CI: 7.10–7.74), diarrhea (ROR: 3.55; 95 % CI: 3.35–3.77), vomiting (ROR: 6.67; 95 % CI: 6.32–7.05) and constipation (ROR: 6.17; 95 % CI: 5.72–6.66).
• Liraglutide had the greatest risk of upper abdominal pain (ROR: 4.63; 95 % CI: 4.12–5.21).
• All GLP-1RAs were associated with pancreatitis risk and were classified as liraglutide (ROR: 32.67; 95 % CI: 29.44–36.25)>  Semaglutide (ROR: 19.10; 95 %-CI: 17.26–21.13)> dulaglutide (ROR: 12.63; 95 % CI: 11.76–13.56)>  Lixisenatide (ROR: 6.78; 95 %-CI: 4.26–10.80)>  Exenatide (ROR: 4.91; 95 % CI: 4.12–5.85).

Limitations

• The data in FAERS are self-reported and cannot prove cause or causality.
• Some data is not available in FAERS.

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