Comparative Safety of Glucagon‐Like Peptide 1 Receptor Agonists (GLP ‐1‐ RAs) in Type 2 Diabetes and Chronic Weight Management: A Real‐World Data Study

📖 Top 20% JournalSep 14, 2025Pharmacoepidemiology and drug safety

Safety of GLP-1 Receptor Agonist Drugs for Type 2 Diabetes and Long-Term Weight Control in Real-World Use

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Abstract

GLP-1 receptor agonist users had hospitalization rates for gallbladder and biliary diseases with risk ratios ranging from 1.14 to 3.32 depending on diabetes status.

Among patients with type 2 diabetes, GLP-1 receptor agonists were associated with a hospitalization rate for gallbladder and biliary diseases, with a risk ratio of 1.14.
In patients without diabetes using chronic weight management regimens, the risk ratio for hospitalization due to gallbladder and biliary diseases was 3.32.
No significant reduction in cardiovascular event rates was found for GLP-1 receptor agonist users, with risk ratios close to 1.00 in both patient groups.
GLP-1 receptor agonist users with type 2 diabetes had a lower rate of acute liver injury, with a risk ratio of 0.76.
The findings suggest an increased risk of specific complications associated with GLP-1 receptor agonists, while showing no cardiovascular benefit.

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PURPOSE: This study assessed serious clinical outcomes comparing glucagon-like peptide 1 receptor agonists (GLP-1-RAs) with sodium glucose co-transporter 2 inhibitors (SGLT2-Is) in patients with type 2 diabetes (T2DM) and patients without diabetes using two chronic weight management (CWM) regimens.

METHODS: We performed a new user, active comparator cohort study in a large, national U.S. claims database. Adults who initiated GLP-1-RAs, SGLT2-Is, naltrexone/bupropion (NalBup), or phentermine/topiramate (PhenTop) from 1 January 2016 to 31 December 2023 were included. Potential confounding was controlled using propensity score weighting for 82 clinical and demographic covariates, and risk ratios (RRs) were estimated.

RESULTS: This study included 330,684 GLP-1-RA users and 264,277 SGLT2-I users with T2DM. Among CWM patients without diabetes, we studied over 25,000 GLP-1-RA users, 5019 NalBup users, and 3841 PhenTop users. In both indications, GLP-1-RA users had higher rates of hospitalizations for gallbladder and biliary diseases with RRs ranging from 1.14 (95% CI: 1.06-1.22) in T2DM patients to 3.32 (95% CI: 1.44-7.64) in CWM patients. No reduction in the rate of cardiovascular events was observed for GLP-1-RA users with RRs ranging from 0.92 (95% CI: 0.37-2.25) in CWM patients to 1.03 (95% CI: 0.99-1.08) in T2DM patients. In T2DM patients, GLP-1-RA users had a lower rate of acute liver injury (RR: 0.76; 95% CI: 0.64-0.91).

CONCLUSIONS: This study corroborates an increased risk of hospitalization for gall bladder and biliary conditions among users of GLP-1-RAs and found similar rates as comparators of MI or stroke when GLP-1-RAs were used for T2DM or CWM. This real-world study complements placebo-controlled trials and can further inform prescribing decisions.

PROTOCOL REGISTRATION: The study protocol was pre-registered at the Center for Open Science's Real-World Evidence Registry and is publicly accessible online (https://doi.org/10.17605/OSF.IO/PSY74).

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