Neutral effects of SGLT2 inhibitors in acute coronary syndromes, peripheral arterial occlusive disease, or ischemic stroke: a meta-analysis of randomized controlled trials

Cardiovasc Diabetol. 2023 Mar 13;22(1):57. doi: 10.1186/s12933-023-01789-5.


Background: Patients with type 2 diabetes are at increased risk for cardiovascular diseases. Sodium-glucose transport 2 inhibitors (SGLT2i) have been shown to enhance cardiovascular health since their debut as a second-line therapy for diabetes. Acute coronary syndrome (ACS), peripheral arterial occlusive disease (PAOD), and ischemic stroke (IS) are types of atherosclerotic cardiovascular disease (ASCVD), although the benefits of treating these disorders have not been shown consistently.

Methods: We searched four databases (PubMed, Embase, the Cochrane library, and for randomized clinical trials (RCTs) until November of 2022. Comparisons were made between SGLT2i-treated and control individuals with type 2 diabetes. Primary outcomes were ACS, PAOD, and IS; secondary outcomes included cardiovascular mortality and all-cause mortality. Risk ratio (RR) and 95% confidence intervals (CI) were determined using a fixed effects model. Cochrane's risk-of-bias (RoB2) instrument was used to assess the validity of each study that met the inclusion criteria.

Results: We enrolled 79,504 patients with type 2 diabetes from 43 RCTs. There was no difference in the risk of ACS (RR = 0.97, 95% CI 0.89-1.05), PAOD (RR = 0.98, 95% CI 0.78-1.24), or IS (RR = 0.95, 95% CI 0.79-1.14) among patients who took an SGLT2i compared to those who took a placebo or oral hypoglycemic drugs. Subgroup analysis revealed that none of the SGLT2i treatments (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) significantly altered outcomes when analyzed separately. Consistent with prior findings, SGLT2i reduced the risk of cardiovascular mortality (RR = 0.85, 95% CI 0.77-0.93) and all-cause mortality (RR = 0.88, 95% CI 0.82-0.94).

Conclusion: Our results appear to contradict the mainstream concepts regarding the cardiovascular effects of SGLT2i since we found no significant therapeutic benefits in SGLT2i to reduce the incidence of ACS, PAOD, or IS when compared to placebo or oral hypoglycemic drugs.

Keywords: Acute coronary syndrome; Canagliflozin; Dapagliflozin; Empagliflozin; Ertugliflozin; Ischemic stroke; Meta-analysis; Peripheral arterial occlusive disease; SGLT2 inhibitor; Type 2 diabetes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome* / complications
  • Acute Coronary Syndrome* / diagnosis
  • Acute Coronary Syndrome* / drug therapy
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / diagnosis
  • Diabetes Mellitus, Type 2* / drug therapy
  • Humans
  • Ischemic Stroke*
  • Randomized Controlled Trials as Topic
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects


  • Sodium-Glucose Transporter 2 Inhibitors

Supplementary concepts

  • Peripheral Arterial Occlusive Disease 1