SGLT2 Inhibitors Linked to Higher Risk of PAD Surgeries Compared to DPP-4 Inhibitors in Veterans with Diabetes: Study

Some placebo-controlled randomized trials have suggested an increased risk of amputation with SGLT2 inhibitors in patients with underlying cardiovascular diseases, though this finding remains unconfirmed by subsequent trials. Considering this, Christianne L. Roumie, Geriatric Research Education Clinical Center, Tennessee Valley Health Care System, Nashville, TN, and colleagues compared the risk of composite peripheral artery disease surgical outcomes, including peripheral revascularization and amputation procedures, between new users of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase 4 inhibitors (DPP-4is).

For this purpose, the researchers conducted a retrospective cohort study of U.S. veterans aged 18 and older with diabetes, receiving care from the Veterans Health Administration, from 2000 to 2021. Data were linked to Medicare, Medicaid, and the National Death Index. The study evaluated the new use of SGLT2is or DPP-4is as an add-on to metformin, sulfonylurea, or insulin treatments, alone or in combination, and its association with PAD surgical procedures, including peripheral revascularization and amputation.

A Cox proportional hazards model for time-to-PAD event analysis was used to compare the risk of PAD events between SGLT2is and DPP-4is in a propensity score-weighted cohort, considering competing risks of death and allowing events to occur up to 90 or 360 days after stopping SGLT2is.

Based on the study, the researchers reported the following findings:

• The weighted cohort included 76,072 episodes of SGLT2i use and 75,833 episodes of DPP-4i use. The median age was 69, with an HbA1c of 8.4% and a median diabetes duration of 10.1 years.
• There were 874 PAD events among SGLT2i users and 780 PAD events among DPP-4i users.
• The event rate was 11.2 per 1,000 person-years for SGLT2i users and 10.0 per 1,000 for DPP-4i users.
• The adjusted hazard ratio (aHR) for PAD events was 1.18 for SGLT2i users compared to DPP-4i users.
• When PAD events were considered for up to 360 days after discontinuing SGLT2i use, the aHR was 1.16.

"We found that the addition of SGLT2 inhibitors as an add-on therapy was associated with a higher risk of amputations, stent placements, or revascularization surgeries compared to DPP-4 inhibitors.," the researchers wrote. They emphasized the importance of assessing the safety of SGLT2 inhibitor use in patients with diabetes who are at very high risk for peripheral artery disease.

Reference:

Katherine E. Griffin, Kathryn Snyder, Amir H. Javid, Amber Hackstadt, Robert Greevy, Carlos G. Grijalva, Christianne L. Roumie; Use of SGLT2i Versus DPP-4i as an Add-On Therapy and the Risk of PAD-Related Surgical Events (Amputation, Stent Placement, or Vascular Surgery): A Cohort Study in Veterans With Diabetes. Diabetes Care 2024; dc241546. https://doi.org/10.2337/dc24-1546