Patient-Oriented Evidence That Matters

SGLT2 Inhibitors Improve All-Cause and Cardiovascular Mortality in Patients Regardless of Diabetes or Heart Failure Status


Am Fam Physician. 2021 May 15;103(10):630-631.

Clinical Question

What effect do sodium-glucose cotransporter-2 (SGLT2) inhibitors have on mortality and cardiovascular and renal outcomes in patients with and without diabetes mellitus, heart failure, or kidney disease?

Bottom Line

SGLT2 inhibitors—medications ending in -flozin, such as canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance), and ertugliflozin (Steglatro)—reduce all-cause and cardiovascular mortality in patients regardless of the presence of type 2 diabetes, heart failure, or chronic kidney disease. Similar mortality reduction occurs in patients with diabetes regardless of comorbid heart failure, and in patients with heart failure regardless of the presence of diabetes. SGLT2 inhibitors also reduce the progression of renal disease in all patients. (Level of Evidence = 1a–)


Two researchers independently searched three databases, including Cochrane CENTRAL, with the bibliographies of identified studies and abstracts of major cardiology meetings, to identify randomized studies in any language that evaluated the impact of treatment with an SGLT2 inhibitor in patients with or without heart failure or type 2 diabetes. Two researchers independently abstracted the data. The researchers followed PRISMA guidelines and assessed the quality of evidence. They included eight studies of 59,747 patients, comprising three studies that included patients without diabetes. Treatment with an SGLT2 inhibitor reduced the risk of mortality due to all causes (hazard ratio [HR] = 0.84; 95% CI, 0.78 to 0.91), cardiovascular mortality (HR = 0.84; 95% CI, 0.76 to 0.93), and hospitalization for heart failure (HR = 0.69; 95% CI, 0.64 to 0.74) compared with placebo, and reduced a composite of end-stage kidney disease, a doubling of the serum creatinine level, and kidney-related mortality (HR = 0.62; 95% CI, 0.56 to 0.70). There were similar mortality and renal benefits for patients with or without diabetes and patients with or without heart failure. Hete

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

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