Utilization patterns of potent GLP-1-RA among patients with type 2 diabetes in clinical practice

Background The potent glucagon-like peptide-1 receptor agonists (GLP-1-RA) semaglutide and tirzepatide have demonstrated to substantially improve health across the cardiovascular-kidney-metabolic (CKM) syndrome. However, their use in clinical practice remains poorly characterized in countries with restrictive reimbursement policies. Purpose To assess the incidence and prevalence of potent GLP-1-RA use among individuals with type 2 diabetes (T2D) and to identify factors associated with treatment initiation in Germany. Methods In this observational cohort study, we analyzed nationwide German statutory health claims data between 2020 and 2024. We included adults aged 18 years or older with type 2 diabetes who had a continuous enrollment for at least one year and no prior use of the study drugs. Factors associated with initiation were estimated using logistic generalized estimating equation models accounting for clustering within calendar quarters, comparing initiators with non-initiators. Results are reported as adjusted odds ratios (aORs) with 95% CIs. Results From 2020 through 2024, 16,799,268 patient-quarter observations from 1,237,576 individuals (mean [SD] age 71.5 [12.6] years; 54% female) were included. Incidence of potent GLP-1-RA initiation increased from 0.26% in the first quarter of 2020 to 0.67% in the fourth quarter of 2024, while prevalence increased from 0.26% to 5.7% in the same period. Initiation was strongly associated with obesity, with a staged increase across classes (aOR 1.99 for class 1, 2.52 for class 2, 3.19 for class 3 vs non-obese individuals). Compared with individuals aged 18-34 years, odds for initiation showed a staged decrease across age groups 35-49, 50-64, and ≥65 years (aOR 0.96, 0.64, and 0.30, respectively). Despite high cardiovascular risk, prior myocardial infarction, stroke, and heart failure were not associated with higher odds of initiation (aOR, 1.02; 0.86; and 0.95, respectively). Chronic kidney disease across stage I to IV was not associated with increased odds of initiation (aOR 0.97 for stage I and II; 0.98 for stage III and IV), as was the case across CKM stages, where aORs remained consistent compared with stage 2 (aOR 0.97 for stage 3; aOR 0.98 for stage 4). By contrast, prior use of other antidiabetic medications was positively associated with initiation, particularly SGLT2 inhibitors and insulins (aOR 2.02, and aOR 2.10, respectively). In a sensitivity analysis restricted to the year 2024, results remained consistent. Conclusions Despite proven cardiometabolic benefits, semaglutide and tirzepatide use in Germany was not preferentially targeted to patients at high cardiovascular risk. Closing this evidence-to-practice gap will require efforts to reduce risk-related disparities in initiating potent GLP-1-RA therapy.