Incident Diabetic Retinopathy after Adjunctive Tirzepatide Treatment for 1 Year in Adults with Type 1 Diabetes

Introduction: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like polypeptide-1 receptor agonist, has significantly increased in use in overweight (OW)/obese people with type 1 diabetes (T1D). It is not known if tirzepatide affects the incidence and/or progression of diabetic retinopathy (DR), including diabetic macular edema (DME), in individuals with T1D. Methods: We performed a retrospective chart review of OW/obese people with T1D using adjunctive tirzepatide treatment continuously for at least 1 year ± 2 months (cases, n = 106). Eighty-five controls with T1D not using tirzepatide were matched by age, sex, and body mass index. Retinal eye examination results were collected at baseline and follow-up (6–24 months). Cases were eligible if temporary drug discontinuations were ≤1 month. For individuals without baseline eye disease, the incidence rates of DR and DME were analyzed. For individuals with baseline DR and/or DME, progression and regression of eye diseases were evaluated. Results: Mean diabetes duration was 26.2 years (cases) and 28.0 years (controls). Baseline DR and/or DME rates were high in both groups (63.2% cases vs. 71.8% controls). Most people in both groups were using an automated insulin delivery system. Mean glycated hemoglobin A1C (HbA1c) improved within 6 months ( P < 0.001) and remained stable for cases, but was unchanged for controls. New-onset DR developed in 10/39 (25.6%) of cases and 7/24 (29.2%) of controls over a mean follow-up of 11.7 and 15.3 months, respectively. Incident DR occurred more frequently in individuals (cases and controls) with a rapid HbA1c decline (≥0.5% within 6 months) compared with those without it (11/28 [39.3%] vs. 6/35 [17.1%], P = 0.048). Among cases and controls with baseline DR, eye disease remained stable at follow-up for most individuals. Conclusions: OW/obese individuals with T1D treated with off-label tirzepatide developed DR similar to controls. Randomized controlled trials are needed to confirm these findings.