SGLT2 Inhibitors Safe After Revascularization for Limb Disease

Miriam E. Tucker, for Medscape

November 11, 2022

The study covered in this summary was published in Research Square as a preprint and has not yet been peer reviewed.

Key Takeaways

  • Compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors were associated with lower risks of cardiac death and composite renal outcomes without increased adverse limb events in patients with type 2 diabetes who had received revascularization for peripheral artery disease (PAD).

Why This Matters

  • Patients with type 2 diabetes and PAD are at increased risk of cardiovascular events and lower limb amputation.

  • SGLT2 inhibitors are recommended for patients at high cardiovascular risk.

  • The SGLT2 inhibitor canagliflozin was associated with a higher rate of amputations compared with placebo in the Canagliflozin Cardiovascular Assessment Study (CANVAS), raising concerns about the general safety of the SGLT2 inhibitor class for patients with type 2 diabetes and concomitant PAD, who are already at increased risk for limb amputation. The boxed warning regarding amputations for canagliflozin added by the US Food and Drug Administration in May 2017 was, however, removed in 2020.

  • Perioperative acute kidney injury has also been reported in patients with PAD who undergo endovascular or surgical revascularization, and renal dysfunction is an independent predictor of adverse outcomes in these patients. 

  • Limited data are available regarding cardiovascular, limb, or renal outcomes when newer glucose-lowering agents such as SGLT2 inhibitors are used in patients with type 2 diabetes after PAD revascularization.

Study Design

  • Nationwide retrospective cohort study with propensity-score matched groups of 1598 patients each who had undergone PAD revascularization and subsequently received first prescriptions of either SGLT2 inhibitors or DPP-4 inhibitors between May 1, 2016 and December 31, 2019.

  • Patients were followed from drug index date until the occurrence of specified outcomes, death, discontinuation of the index drug, or the end of the study period, whichever occurred first.

Key Results

  • The SGLT2 inhibitor group had a significantly lower incidence of cardiac death compared with the DPP-4 inhibitor group (1.23 vs 2.12 per 100 person-years; hazard ratio 0.60; P = .0126).

  • The SGLT2 inhibitor and DPP4 inhibitor groups had comparable incidence rates of ischemic stroke (1.87 vs 1.81 per 100 person-years; P = .8146), acute myocardial infarction (1.50 vs 1.67 per 100 person-years; P = .5946), and hospitalization for heart failure (2.76 vs 2.14 per 100 person-years; P = .1014).

  • The two groups had comparable cumulative risks of repeated revascularization (5.63 vs 6.67 per 100 person-years; P = .1602) and lower limb amputation (1.25 vs 1.60 per 100 person-years; P = .3358).

  • The SGLT2 inhibitor group had a lower cumulative risk of composite renal outcomes compared with the DPP-4 inhibitor group (1.08 vs 2.84 per 100 person-years; P < .0001).

  • Results were consistent with the main analysis for most outcomes in a subgroup analysis for patients aged ≥ 75 years, those with chronic kidney disease (CKD), female patients, and those taking statins (P interaction > 0.05).


  • Propensity score matching could not account for confounders such as prescribing behavior or drug adherence. 

  • Observational, potentially subject to time-related biases.

  • No A1c data.

  • Severity of CKD unknown.

  • Possible miscoding of comorbidities/outcomes.

  • Homogenous Asian study population.


  • Study funding: Ministry of Science and Technology, Taiwan, and Chang Gung Memorial Hospital.

  • Author disclosures: None.

This is a summary of a preprint research study, "Adverse cardiovascular, limb, and renal outcomes in patients with diabetes after peripheral artery disease revascularization treated with sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors," by Hsin-Fu Lee, of New Taipei City Municipal Tucheng Hospital, Taiwan, and colleagues provided to you by Medscape. The study has not yet been peer reviewed.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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