This network study did not find an increased diabetic retinopathy risk with semaglutide in adults with type 2 diabetes and found some lower risks versus specific comparators.
Evidence
A retrospective active-comparator cohort study across 14 OHDSI claims and electronic health record databases, including 810,390 new semaglutide users, found similar risk versus dulaglutide, empagliflozin, and sitagliptin, lower risk versus glipizide, and treatment-requiring /DME risk similar to empagliflozin but lower than dulaglutide, sitagliptin, and glipizide.
Caveat
This was observational network evidence with mixed comparator-specific results, so it cannot exclude residual confounding or prove semaglutide lowers retinopathy risk across all drug comparisons.
Simplified
INTRODUCTION: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) used to treat type 2 diabetes mellitus (T2D), has potential associations with higher rates of diabetic retinopathy () complications including proliferative DR () and diabetic macular edema (DME). The purpose of this study was to determine whether an association exists between semaglutide and PDR and treatment-requiring DR/DME.
RESEARCH DESIGN AND METHODS: This was a retrospective cohort study of 14 databases (six administrative claims and eight electronic health records) in the Observational Health Data Sciences and Informatics Evidence Network. Adults with T2D on semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from 1 December 2017 to 31 December 2023 were included. The association between semaglutide and PDR or treatment-requiring DR/DME was assessed using an active-comparator cohort design comparing new users of semaglutide as second-line T2D treatment to those on other GLP-1RAs and non-GLP-1RAs. Propensity score-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs). Network-wide HR estimates were generated using a random-effects meta-analysis.
RESULTS: The study included 810 390 new semaglutide users for T2D. PDR risk for semaglutide was similar to dulaglutide (HR 0.81, 95% CI 0.42 to 1.54, p=0.51), empagliflozin (HR 0.83, 95% CI 0.53 to 1.30, p=0.41) and sitagliptin (HR 0.83, 95% CI 0.45 to 1.55, p=0.57) but was lower than glipizide (HR 0.59, 95% CI 0.39 to 0.88, p=0.01). The risk for treatment-requiring DR/DME for semaglutide was similar to empagliflozin (HR 0.66, 95% CI 0.43 to 1.02, p=0.06) but lower than dulaglutide (HR 0.53, 95% CI 0.31 to 0.91, p=0.02), sitagliptin (HR 0.46, 95% CI 0.26 to 0.81, p=0.008) and glipizide (HR 0.55, 95% CI 0.33 to 0.91, p=0.02).
CONCLUSIONS AND RELEVANCE: We did not identify increased risk for either PDR or treatment-requiring DR/DME comparing semaglutide with other GLP-1RAs or non-GLP-1RAs. Patients with T2D should still undergo close eye care follow-up, particularly when initiating new antihyperglycemic medications.
Key numbers
0.59
Risk for vs. glipizide
() for in semaglutide users compared to glipizide.
0.53
Risk for treatment-requiring / vs. dulaglutide
() for treatment-requiring / in semaglutide users compared to dulaglutide.
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