Independent effects of 15 commonly prescribed drugs on all-cause mortality among US elderly patients with type 2 diabetes mellitus

OBJECTIVE: Most patients with type 2 diabetes mellitus (T2DM) also have hypertension and hyperlipidemia. Consequently, they are taking medications for all three conditions concurrently and the effect of one drug could be confounded with that of another. This study aimed to determine the independent effects of 15 commonly prescribed medications for three conditions on the risk of all-cause mortality among elderly patients with T2DM. RESEARCH DESIGN AND METHODS: A cohort of 360 437 elderly patients with T2DM from 2007 to 2016 US Medicare data was traced along with cumulative uses of 8 diabetes, 6 hypertension and 1 hyperlipidemia drugs. The relative risk of all-cause mortality for each study drug was estimated using an extended Cox regression analysis adjusting for the concurrent use of other study drugs. RESULTS: Compared with the no use of each study medication, mortality risk declined with use of 3 diabetes drugs, sodium-glucose cotransporter-2 inhibitors (HR=0.73; 95% CI 0.64 to 0.84), glucagon-like peptide-1 receptor agonists (HR=0.75; 95% CI 0.70 to 0.80) and dipeptidyl peptidase-4 inhibitors (HR=0.94; 95% CI 0.91 to 0.98), the use of 3 blood pressure medications, diuretics (HR=0.89; 95% CI 0.87 to 0.92), angiotensin receptor blockers (HR=0.86; 95% CI 0.84 to 0.89), ACE inhibitors (HR=0.98; 95% CI 0.95 to 1.01) as well as statins (HR=0.83; 95% CI 0.80 to 0.85). It increased moderately with insulin (HR=1.55; 95% CI 1.51 to 1.59), sulfonylureas (HR=1.16; 95% CI 1.13 to 1.20), a small inconsistent amount with metformin (HR=1.05), beta-blockers (HR=1.07), dihydropyridine calcium-channel blockers (HR=0.99) and non-dihydropyridine calcium-channel blockers (HR=1.05). The use of thiazolidinedione had no effect. CONCLUSION: Among older patients with diabetes, mortality risk decreased importantly with three new diabetes drugs, 3 blood pressure drugs and statins. It increased moderately with sulfonylurea and insulin. Studies of aggressive use of new T2DM drugs instead of sulfonylureas and insulin are needed. Our statin results empirically validate two national guidelines for using statins in older patients with diabetes. However, 23% of study patients never took a statin, suggesting missed opportunities for prevention.