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Comparative Safety of Glucagon-Like Peptide 1 Receptor Agonists (GLP-1-RAs) in Type 2 Diabetes and Chronic Weight
Sarah Ruth Hurwitz1, Stephan Lanes1, Tracey Quimbo1
1Carelon Research, Wilmington, Delaware, USA.
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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