Sodium-Glucose Cotransporter 2 Inhibitors: An Overview

Essie Samuel, PharmD, BCPS; Jiehyun Lee, PharmD, BCACP, CACP


US Pharmacist. 2017;42(10):42-47. 

In This Article

Sglt2 Inhibitors and CV Outcomes

One study that evaluated the CV benefit of SGLT2 inhibitors was the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients.[17] This RCT examined the effect of empagliflozin on CV morbidity and mortality in older patients with long-standing T2DM and established CV disease. Approximately 7,000 adults were randomized to one of three groups (empagliflozin 10 mg daily, empagliflozin 25 mg daily, or placebo) and followed for a median of 3.1 years. The primary outcome was a composite of deaths from CV causes, nonfatal myocardial infarction (MI) excluding silent MI, and nonfatal stroke.[17]

In this RCT, the pooled empagliflozin group had significantly lower mortality rates than the placebo group (14% reduction in composite death). Also, a significant reduction in death from CV causes was observed in the pooled empagliflozin group (3.7% vs. 5.9% in the placebo group, translating to a 38% relative risk reduction) that was primarily driven by lower rates of heart failure–related hospitalization or death.[17] In December 2016, as a result of empagliflozin's potential CV benefits, the FDA approved an expanded indication for empagliflozin to reduce the risk of CV death in adult patients with T2DM and established CV disease.

More recently, another cardiovascular-outcome trial of SGLT2 inhibitors, the Canagliflozin Cardiovascular Assessment Study, was completed. This RCT included more than 10,000 patients with T2DM and high CV risk who were randomized to either canagliflozin or placebo and followed for a mean of 3.6 years. The rate of the primary outcome—a composite of death from CV causes, nonfatal MI, or nonfatal stroke—was reduced by 14%, and it was concluded that canagliflozin may confer a renal benefit. However, there was an almost twofold increase in the risk of amputation (mainly at the level of the toe or metatarsal) with canagliflozin use.[18]

These two trials have shown CV benefits from SGLT2 inhibitors. It is, however, premature to conclude that this CV benefit is a drug-class effect of SGLT2 inhibitors; future CV-outcome studies of SGLT2 inhibitors will help determine this.