Abstract
Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have rapidly expanded from primarily glucose-lowering agents for type 2 diabetes (T2D) to therapies used across diabetes, obesity, and cardiometabolic disease. Prescribing has risen sharply since 2018, especially with the broader uptake of semaglutide-based products. Still, real-world initiation patterns remain incompletely characterized in older adults with varying levels of cognitive vulnerability and frailty.
Methods: We analyzed treatment patterns of GLP-1RA use in a retrospective cohort of adults aged >=65 years with T2D in a regional healthcare system from 2018 to 2026. We describe the demographic and clinical characteristics of new initiators of GLP-1RAs compared with initiators of alternative therapies, including sodium-glucose cotransporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i). We analyzed a sub-cohort of patients to identify the prevalence of baseline cognitive concerns using a large language model (LLM). We used a LASSO logistic regression to identify important predictors of GLP-1RA initiation compared to other therapies.
Results: Of 58,754 adults aged 65 years or older with T2D, 5,095 initiated GLP-1RA, 5,483 initiated a SGLT2 inhibitor, and 1,516 initiated a DPP-4 inhibitor. GLP-1RA initiators were younger (mean 75.2 [SD 4.9] vs 77.7 [6.0] and 79.5 [7.1] years) and less often aged 80 years or older (17.7% vs 35.0% and 47.6%). The largest difference across groups was adiposity: mean BMI was 33.8 (6.2) vs 29.7 (5.7) and 28.6 (5.6) kg/m2 (SMD 0.592), with a BMI of 30 kg/m2 or higher in 72.1% vs 41.9% and 34.0%. Glycemic control was similar (mean HbA1c 7.46% vs 7.38% and 7.70%; SMD 0.165). GLP-1RA initiators were younger; more likely to be overweight; had lower average comorbidity index; and less dementia, heart failure, and renal disease than those initiating alternative therapies. GLP-1RA initiators had fewer hospitalizations 1-year prior to drug initiation. In a LASSO model, BMI greater than 27 kg/m2 was the strongest predictor of GLP-1RA initiation (positive), followed by baseline congestive heart failure (negative) and baseline hospitalization (negative).
Conclusion: In this cohort of older adults, those with T2D who initiated GLP-1RAs were younger and had less comorbidities at baseline compared to initiators of other T2D therapies. Overweight BMI was the strongest predictor of GLP-1RAs initiation, whereas baseline HbA1c was similar across groups, suggesting that the decision to start GLP1-RA is more influenced by adiposity than glycemic control. Our analysis of real-world prescribing patterns appear to be in alignment with guidelines for Type II diabetes treatment1, which recommend GLP-1RA treatment for glucose lowering and weight management and SGLT2 treatment in those with risk of cardiovascular disease or heart failure.