Popular Diabetes Drug May Raise Vascular Surgery Risk

TOPLINE:

Among older veterans with type 2 diabetes (T2D), the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors as an add-on therapy is associated with a higher risk for peripheral artery disease (PAD)-related surgical events than the use of dipeptidyl peptidase 4 (DPP-4) inhibitors.

METHODOLOGY:

• Some placebo-controlled randomized trials have reported an increased risk for amputation with the use of SGLT2 inhibitors in patients with underlying cardiovascular diseases; however, the evidence remains unconfirmed by other subsequent trials.
• Researchers conducted a retrospective study of US veterans with T2D initiating SGLT2 inhibitors or DPP-4 inhibitors (a reference drug) as an add-on to metformin, sulfonylurea, or insulin treatment alone or in combination.
• The primary outcome was the time to the first surgical event for PAD (amputation, peripheral revascularization and bypass, or peripheral vascular stent).
• A Cox proportional hazards model was used to compare PAD event risk between the SGLT2 inhibitor and DPP-4 inhibitor groups, allowing events up to 90 days or 360 days after stopping SGLT2 inhibitors.

TAKEAWAY:

• After propensity score weighting, 76,072 episodes of SGLT2 inhibitor use (94% empagliflozin, 4% canagliflozin, and 2% dapagliflozin) and 75,833 episodes of DPP-4 inhibitor use (45% saxagliptin, 34% alogliptin, 15% sitagliptin, and 6% linagliptin) were included.
• Participants had a median age of 69 years and a median duration of diabetes of 10.1 years.
• SGLT2 inhibitor users had higher PAD-related surgical events than DPP-4 inhibitor users (874 vs 780), with event rates of 11.2 vs 10.0 per 1000 person-years (adjusted hazard ratio [aHR], 1.18).
• The cumulative probability of PAD-related surgical events at 4 years was higher for SGLT2 inhibitor users than for DPP-4 inhibitor users (4.0% vs 2.8%, respectively).
• The results remained consistent after 90 and 360 days of stopping SGLT2 inhibitors.
• SGLT2 inhibitor use was also associated with a higher risk for amputation (aHR, 1.15) and revascularization (aHR, 1.25) events than DPP-4 inhibitor use.

IN PRACTICE:

“These results underscore the need to determine the safety of [SGLT2 inhibitor] use among patients with diabetes who remain at very high risk for PAD,” the authors wrote.

SOURCE:

This study was led by Katherine E. Griffin, Geriatric Research Education and Clinical Center, Tennessee Valley Healthcare System, Nashville, Tennessee, and published online in Diabetes Care.

LIMITATIONS:

The study excluded patients whose initial diabetes treatment was not metformin, insulin, or sulfonylurea, which might have influenced the interpretation of the results. The median follow-up period of approximately 0.7 years for both groups may have affected the number of amputations and revascularization events observed. The study population primarily comprised White men, limiting generalizability to women and other demographic groups.

DISCLOSURES:

The study received funding through an investigator-initiated grant from the Veterans Affairs Clinical Science Research and Development. Two authors received partial research support through a grant from the Center for Diabetes Translation Research. All authors received partial support from the VETWISE-LHS Center of Innovation. No potential conflicts of interest relevant to the article were reported.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.