Prescribing preferences for antidiabetic medications among older Type 2 Diabetes (T2D) patients with Alzheimer’s Disease (ADRD) and multimorbidity, 2013-2019

Background: Older adults with T2D face high levels of multimorbidity burden and are more likely to be diagnosed with ADRD. In recent years, select antidiabetic agents, such as glucagon-like peptide-1 receptor agonist (GLP-1RA) and sodium-glucose cotransporter-2 inhibitor (SGLT2i) have demonstrated efficacy in reducing the risk of cardiorenal disease and mortality for older adults with T2D. Despite growing recommendations for use in this demographic, there is a paucity of data evaluating uptake by in those with high multimorbidity and ADRD.

Objectives: To evaluate the initiation patterns of antidiabetic medications by multimorbidity levels and Alzheimer’s Disease (ADRD) status.

Methods: We used Medicare fee-for-service (2013-2019) data to identify a cohort of older T2D patients newly initiating the following second-line antidiabetic medications: SGLT2i, GLP-1RA, dipeptidyl peptidase-4 inhibitor (DPP4i), sulfonylureas (SU), thiazolidinediones. Initiation trends were analyzed based on presence of ADRD and by severity of multimorbidity. Finally, we estimated the odds ratio of initiating either SGLT2i or GLP-1RA in patients with cardiorenal diseases, adjusted for sociodemographic, medical conditions, and multimorbidity.

Results: Among 1,788,762 T2D patients, SU initiations declined significantly by 24.4% (50.3% in 2013 to 25.8% in 2019), and largely offset by an increase in SGLT2i initiations by 20.8% (1.3% to 22.0%); however, these shifts towards SGLT2i and newer cardiorenal agents were less pronounced in patients with ADRD (n=180,512) versus those without ADRD (n=1,549,100). By 2019, individuals with ADRD favored DPP4i as the most initiated medication, with a 13.3% higher initiation rate compared to those without ADRD (34.3% vs. 21.0%); as a result, those with ADRD were less likely to initiate SGLT2i and GLP-1RA by 8.0% (14.4% vs. 22.4%) and 5.9% (17.1% vs. 23.0%), respectively. Higher multimorbidity correlated with increased DPP4i utilization and decreased SGLT2i utilization. When adjusted for age, race, and other comorbidities, patients with both severe and moderate multimorbidity had increased odds of initiating SGLT2i or GLP-1RA compared to mild, though the OR (95% CI) was lower in those with severe [1.24 (1.22,1.26)] versus moderate multimorbidity [1.34 (1.32,1.36)].

Conclusions: Initiation of newer T2D agents increased regardless of ADRD presence, but with diminished likelihood in severe multimorbidity. This reduced adoption may stem from unique clinical challenges (e.g., distinctive adverse reactions) and high cost in a medically complex population, and limited evidence in older, multimorbid patients due to trial exclusion or underrepresentation, warranting further investigation in multimorbidity and its impact on prescribing.