The website may be down at times on Saturday, December 14, and Sunday, December 15, for maintenance. 

brand logo

Am Fam Physician. 2016;93(5):410

Clinical Question

In patients with type 2 diabetes mellitus and cardiovascular (CV) disease, does the addition of empagliflozin (Jardiance) improve outcomes?

Bottom Line

In patients with established CV disease and type 2 diabetes, the addition of empagliflozin to standard therapy reduces all-cause mortality and CV mortality. This is notable because empagliflozin is the only drug other than metformin to demonstrate a mortality benefit, albeit for a fairly narrow group of patients. A dose of 10 mg appears to provide a similar benefit to the 25-mg dose, but with half the risk of genital infections. It is not appropriate to extend these conclusions to all patients with type 2 diabetes, because they are at lower risk of bad outcomes and are unlikely to benefit to the same degree. (Level of Evidence = 1b)

Synopsis

Empagliflozin decreases reabsorption of glucose in the kidneys, leading to greater urinary excretion. In this industry-sponsored trial, adults with type 2 diabetes and known CV disease were randomized to receive empagliflozin, 10 mg; empagliflozin, 25 mg; or placebo. The 7,028 patients were recruited from 590 sites in 42 countries. The mean age of participants was 63 years, 71% were men, and 5% were black. This was a very high-risk group: 75% had coronary artery disease, 23% had a previous stroke, 20% had peripheral arterial disease, and 25% had a coronary artery bypass graft. The other hypoglycemic medications used by patients included metformin (75%), insulin (53%), or a sulfonylurea (43%). Outcomes were adjudicated by a committee masked to treatment assignment, and analysis was by modified intention to treat for all patients who received at least one dose of the study drug.

The primary outcome was a composite of myocardial infarction, stroke, or CV death. Patients were followed for a median of 3.1 years. Results for the two empagliflozin doses were pooled and compared with placebo. The patients in the intervention groups had lower all-cause mortality (5.7% vs. 8.3%; P < .001; number needed to treat [NNT] = 38 over 3.3 years), CV mortality (3.7% vs. 5.9%; P < .001; NNT = 45 over 3.3 years), and hospitalization for heart failure (2.7% vs. 4.1%; P = .002; NNT = 71 over 3.3 years). There were no differences in other outcomes, including myocardial infarction, stroke, coronary revascularizations, or transient ischemic attacks. The pooled dropout rate due to adverse events was 11.5% for the study drug and 13.0% for placebo. There were more episodes of urosepsis or pyelonephritis in the empagliflozin groups (0.8% vs. 0.5%), and far more genital infections (5.0% vs. 1.5% in men; 10.0% vs. 2.6% in women).

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry

Allocation: Concealed

Setting: Outpatient (any)

Reference: ZinmanBWannerCLachinJMet alEMPA-REG OUTCOME InvestigatorsEmpagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med2015; 373( 22): 2117– 2128.

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.

For definitions of levels of evidence used in POEMs, see https://www.essentialevidenceplus.com/Home/Loe?show=Sort.

To subscribe to a free podcast of these and other POEMs that appear in AFP, search in iTunes for “POEM of the Week” or go to http://goo.gl/3niWXb.

This series is coordinated by Natasha J. Pyzocha, DO, contributing editor.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.

Continue Reading


More in AFP

More in PubMed

Copyright © 2016 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See permissions for copyright questions and/or permission requests.