Title:Empagliflozin for Type 2 Diabetes Mellitus: An Overview of Phase 3 Clinical Trials
Volume: 13
Issue: 4
Author(s): Matthew J. Levine*
Affiliation:
- 10666 North Torrey Pines Road, La Jolla, CA 92037,United States
Keywords:
Empagliflozin, phase 3, sodium glucose cotransporter 2, SGLT2 inhibitor, type 2 diabetes mellitus.
Abstract: Introduction: Sodium glucose cotransporter 2 (SGLT2) inhibitors have a unique
mechanism of action leading to excretion of glucose in the urine and subsequent lowering of
plasma glucose. This mechanism is independent of β-cell function; thus, these agents are effective
treatment for type 2 diabetes mellitus (T2DM) at theoretically any disease stage. This class should
not confer an additional risk of hypoglycemia (unless combined with insulin or an insulin secretagogue)
and has the potential to be combined with other classes of glucose-lowering agents.
Empagliflozin is one of three currently approved SGLT2 inhibitors in the United States, and has
shown a favorable benefit-risk ratio in phase 3 clinical trials as monotherapy and as add-on to other
glucose-lowering therapy in broad patient populations. In addition to its glucose-lowering effects,
empagliflozin has been shown to reduce body weight and blood pressure without a compensatory
increase in heart rate. Moreover, on top of standard of care, empagliflozin is the first glucoselowering
agent to demonstrate cardiovascular risk reduction in patients at high risk of cardiovascular
disease in a prospective outcomes trial: a 14% reduction in risk of the 3-point composite endpoint
of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Like
other SGLT2 inhibitors, empagliflozin is associated with a higher rate of genital mycotic infections
than placebo and has the potential for volume depletion–associated events.
Conclusion: This review summarizes the empagliflozin phase 3 clinical trials program and its potential
significance in the treatment of patients with T2DM. Evidence from these clinical trials
show reductions in glycated hemoglobin (–0.59 to –0.82%) with a low risk of hypoglycemia except
when used with insulin or insulin secretagogues, and moderate reductions in body weight (–2.1 to –
2.5 kg) and systolic blood pressure (–2.9 to –5.2 mm Hg), thus supporting the use of empagliflozin
as monotherapy or in addition to other glucose-lowering agents. In addition, evidence from the recent
EMPA-REG OUTCOME study, which demonstrated relative risk reductions in major adverse
cardiac events (14%), cardiovascular mortality (38%) and all-cause mortality (32%), as well as
hospitalization for heart failure (36%), supports use of empagliflozin in patients with T2DM and
increased cardiovascular risk.