Outcomes of GLP-1 receptor agonist therapy in adults with sickle cell disease and type 2 diabetes: a real-world cohort analysis

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PURPOSE: Outcomes of patients with sickle cell disease (SCD) and type 2 diabetes mellitus (T2DM) treated with glucagon-like peptide-1 (GLP1-RA) remain poorly understood. This study evaluated the impact of GLP-1 on adults with SCD and T2DM beyond glycemic control. METHODS: We conducted a retrospective study within the TriNetX Network, identifying adults with SCD and T2DM. GLP-1 users and non-GLP-1 users were matched using Propensity score matching. The index date was defined as the first GLP-1 prescription, and outcomes were assessed over 12 months. Outcomes were major adverse cardiovascular events (MACE), chronic kidney disease (CKD), vaso-occlusive crises (VOC), and hypoglycemia. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: We included 1,391 patients in each cohort, with similar age (48.5 vs. 48.8), and most participants were Black (84.5% vs. 83.8%). GLP-1 therapy was associated with lower risk of MACE (HR 0.61, 95% CI 0.49-0.76; P < 0.00001) and a reduced risk of stroke (HR 0.47, 95% CI 0.23-0.97; P = 0.036). Additionally, GLP-1 use was linked to a 36% lower risk of VOC (HR 0.64, 95% CI 0.45-0.91; P = 0.013). There was no difference in risk of hypoglycemia (HR 1.10, 95% CI 0.60-1.76; P = 0.688) or progression to CKD between the two groups (HR 1.26, 95% CI 0.82-1.95; P = 0.294). CONCLUSIONS: GLP-1 therapies demonstrate favorable cardioprotective, vaso stabilizing, and safety benefits in adults with SCD and T2DM, supporting their use in this high-risk population. CLINICAL TRIAL NUMBER: Not applicable.

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