Cardiovascular Safety of DPP-4 Inhibitors vs. Insulin or Sulfonylureas in Elderly Diabetes Patients

Strategic Insights -

Research conducted by the University of South Australia has found that dipeptidyl peptidase 4 (DPP-4) inhibitors are equally safe as long-acting insulin or sulfonylureas when added to metformin in older people with diabetes living in long-term care facilities. The study, published in the Journal of the American Medical Directors Association, compared the cardiovascular safety of DPP-4 inhibitors with long-acting insulin and sulfonylureas among individuals aged 65 years with diabetes who entered long-term care facilities between 2009 and 2018. The results showed that DPP-4 inhibitors had a similar risk of hospitalization for heart failure and major adverse cardiovascular events (MACEs) as long-acting insulin or sulfonylureas, but with a lower risk of hypoglycemia and all-cause mortality compared to long-acting insulin.

Key Takeaways:

  • DPP-4 inhibitors have a similar cardiovascular safety profile to long-acting insulin or sulfonylureas when added to metformin in older people with diabetes living in long-term care facilities.
  • The risk of hospitalization for heart failure and MACEs was similar between DPP-4 inhibitors and long-acting insulin or sulfonylureas (0.98-1.25 and 0.95-1.10, respectively).
  • DPP-4 inhibitors had a 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) compared to long-acting insulin.
  • The study included 4414 initiators of DPP-4 inhibitors compared to insulin and 2686 initiators of DPP-4 inhibitors compared to sulfonylureas.
  • The results support the preferential use of DPP-4 inhibitors over long-acting insulin as add-on therapy to metformin in older people with diabetes living in long-term care facilities.

Statistics:

  • The study included 4414 initiators of DPP-4 inhibitors compared to insulin and 2686 initiators of DPP-4 inhibitors compared to sulfonylureas.
  • The risk of hospitalization for heart failure was 0.98 (95% CI, 0.77-1.25) among initiators of DPP-4 inhibitors compared to insulin.
  • The risk of MACEs was 0.95 (95% CI, 0.83-1.10) among initiators of DPP-4 inhibitors compared to insulin.
  • The risk of hypoglycemia was 0.36 (95% CI, 0.23-0.56) among initiators of DPP-4 inhibitors compared to long-acting insulin.
  • The risk of all-cause mortality was 0.82 (95% CI, 0.76-0.90) among initiators of DPP-4 inhibitors compared to long-acting insulin.

Sources:

  • Journal of the American Medical Directors Association (2025): "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."
  • University of South Australia (Source not specified but presumably UniSA Allied Health and Human Performance, University of South Australia, Adelaide, South Australia, Australia)
  • Journal of the American Medical Directors Association (Journal of the American Medical Directors Association can be contacted at: Elsevier Science Inc, Ste 800, 230 Park Ave, New York, NY 10169, USA.)
  • NewsRx (NewsRx. New Findings from University of South Australia Yields New Data on Heart Failure (Cardiovascular Safety of Dipeptidyl Peptidase 4 Inhibitors Compared With Insulin or Sulfonylureas Added to Metformin Among Older People With Diabetes Living in ...). Cardiovascular Week. October 27, 2025; p 275).