Cardiovascular Safety of Dipeptidyl Peptidase 4 Inhibitors Compared With Insulin or Sulfonylureas Added to Metformin Among Older People With Diabetes Living in Long-Term Care Facilities

Objectives To examine the cardiovascular safety of dipeptidyl peptidase 4 (DPP-4) inhibitors compared with long-acting insulin or sulfonylurea initiation added to metformin in older people with diabetes in long-term care facilities (LTCFs). Design A new-user multiple active comparator retrospective cohort study of the cardiovascular safety of DPP-4 inhibitors compared with long-acting insulin and sulfonylureas when added to metformin. Setting and Participants Individuals aged ≥65 years with diabetes who entered LTCFs between January 1, 2009, and December 31, 2018, were included within the Registry of Senior Australians National Historical cohort. Methods Time to hospitalization for heart failure or major adverse cardiovascular events (MACEs) (a composite of nonfatal stroke, nonfatal myocardial infarction or cardiovascular mortality) over a 5-year follow-up period was compared between matched DPP-4 inhibitors and long-acting insulin or sulfonylurea users. Fine-Gray models were used to estimate subdistribution hazard ratios (sHRs). Results Among initiators of DPP-4 inhibitors compared with insulin (n = 4414), the risk of hospitalization for heart failure was 0.98 (95% CI, 0.77-1.25), whereas the risk of MACEs was 0.95 (95% CI, 0.83-1.10). Among initiators of DPP-4 inhibitors compared with sulfonylureas (n = 2686), the risk of hospitalization for heart failure was 1.08 (95% CI, 0.79-1.49), whereas the risk of MACEs was 0.93 (95% CI, 0.77-1.12). Lower risk of hypoglycemia (sHR, 0.36; 95% CI, 0.23-0.56) and all-cause mortality (sHR, 0.82; 95% CI, 0.76-0.90) was observed in DPP-4 initiators compared with long-acting insulin. Conclusions and Implications In residents of LTCFs receiving metformin, initiation of DPP-4 inhibitors was associated with a similar 5-year cardiovascular risk to long-acting insulin or sulfonylurea, but with a lower risk of hypoglycemia and all-cause mortality compared with long-acting insulin. These findings support the preferential use of DPP-4 inhibitors over long-acting insulin as add-on therapy to metformin in older people with diabetes in LTCFs.