Polypharmacy and age predict MACE in rural Montana type 2 diabetes cohort

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medRxiv Published April 4, 2026 Medically reviewed April 26, 2026 Study authors: Li, J. W.; Crew, L. A.; Cox, T. M.; Canine, B. F. DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider medication count and age as predictors of MACE in rural diabetes patients, but recognize these are observational associations.

This observational cohort study analyzed 591 patients with type 2 diabetes from the Big Sky Care Connect Database in rural Montana. Patients were stratified by prescribed medication count: 1-4 medications (non-polypharmic), 5-9 medications (polypharmic), and ≥10 medications (hyperpolypharmic). The primary outcome was not explicitly stated, but secondary outcomes included Major Adverse Cardiovascular Events (MACE) and Diabetes Complication Severity Index (DCSI).

Multivariate analysis showed medication count and age were significant predictors of MACE, with an incidence rate ratio (IRR) of 1.06 per additional medication and 1.03 per year of age (p < 0.001 for both). Neuropathy and nephropathy prevalence also increased significantly across patient cohorts with higher medication counts (p < 0.001). Medication count was negatively associated with male gender (β = -2.1341, p < 0.001).

Safety and tolerability data were not reported. Key limitations include the observational design, which cannot establish causality, and the lack of reported follow-up duration. The study population was specific to rural Montana, which may limit generalizability. Funding sources and conflicts of interest were not reported.

For practice, these findings highlight associations between polypharmacy and adverse outcomes in a rural diabetes population. The results may inform strategies to improve medication adherence and reduce preventable complications in underserved regions, but clinical decisions should not be based solely on these observational associations.

Study Details

Study typeCohort

Sample sizen = 591

EvidenceLevel 3

PublishedApr 2026

View Original Abstract ↓

Objective: In this study, we utilized a large-scale clinical database to evaluate the relationship between polypharmacy and adverse outcomes among type 2 diabetes patients in rural Montana to inform strategies that improve adherence, reduce preventable complications, and promote equitable diabetes care in underserved regions. Research Design and Methods: 591 patients from the Big Sky Care Connect Database (BSCC) with type 2 diabetes and medication history were stratified into 3 cohorts based on prescribed number of medications: (1-4 medications, non-polypharmic), (5-9 medications, polypharmic), and ([≥]10 medications, hyperpolypharmic). Each cohort was examined for Major Adverse Cardiovascular Events (MACE) and Diabetes Complication Severity Index (DCSI). Descriptive statistics, multivariate logistic regressions, linear regression, and Poisson regression analyses were performed. Results: Medication count was associated with male gender ({beta} = -2.1341, p < 0.001). Both medication count (IRR 1.06 per additional medication, p < 0.001) and age (IRR 1.03 per year, p < 0.001) were significant predictors of MACE. Neuropathy and nephropathy prevalence was statistically significant (p < 0.001) across patient cohorts and increased with medication count.