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Am Fam Physician. 2023;107(1):81-82

Author disclosure: No relevant financial relationships.

Clinical Question

Do sodium-glucose cotransporter-2 (SGLT-2) inhibitors improve cardiovascular outcomes in patients who have heart failure with preserved ejection fraction (HFpEF)?

Evidence-Based Answer

SGLT-2 inhibitors can reduce hospitalizations from heart failure but do not significantly reduce cardiovascular-related mortality. (Strength of Recommendation [SOR]: A, based on three meta-analyses of seven randomized controlled trials [RCTs] and one high-quality RCT.) Dapagliflozin (Farxiga) decreases symptoms of heart failure and improves distance walked in a six-minute walk test (mean increase = 8.3%). (SOR: B, based on one good-quality RCT.)

Evidence Summary

A 2020 systematic review and meta-analysis included two RCTs and a pooled analysis of two additional RCTs evaluating the effect of SGLT-2 inhibitors compared with placebo in patients who had heart failure with reduced ejection fraction and HFpEF.1 The authors performed subgroup analyses of patients with preserved ejection fraction (n = 2,554). Patients (average age = 64 to 70 years) with diabetes mellitus and an ejection fraction greater than 45% were randomized to treatment with ertugliflozin (Steglatro), 5 or 15 mg per day; dapagliflozin, 10 mg per day; sotagliflozin (Zynquista; not available in the United States), 200 or 400 mg per day; or placebo with a follow-up of nine to 50 months. The primary outcome, a composite of hospitalization for heart failure and cardiovascular mortality, was not significantly different between the SGLT-2 inhibitors and placebo (four studies; n = 2,554; hazard ratio [HR] = 0.80; 95% CI, 0.63 to 1.00; P = .05). The SGLT-2 inhibitors did reduce the first hospitalization from heart failure (two studies; n = 1,815; HR = 0.71; 95% CI, 0.52 to 0.97; P = .03) but did not decrease cardiovascular mortality (two studies; n = 1,815; HR = 1.27; 95% CI, 0.92 to 1.76; P = .15). The validity of the primary outcome was limited by significant heterogeneity (I2 = 63.9%).

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Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (

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