Email updates

Keep up to date with the latest news and content from Cardiovascular Diabetology and BioMed Central.

Open Access Highly Accessed Study protocol

Rationale, design and baseline characteristics of a 4-year (208-week) phase III trial of empagliflozin, an SGLT2 inhibitor, versus glimepiride as add-on to metformin in patients with type 2 diabetes mellitus with insufficient glycemic control

Martin Ridderstråle1*, Robbyna Svaerd2, Cordula Zeller3, Gabriel Kim4, Hans J Woerle4, Uli C Broedl4 and on behalf of the EMPA-REG H2H-SU™ trial investigators

Author Affiliations

1 Steno Diabetes Center, Niels Steensens Vej 2-4, DK-2820, Gentofte, Denmark

2 Boehringer Ingelheim AB, Liljeholmsstrand 3, 11743, Stockholm, Sweden

3 Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88397, Biberach/Riß, Germany

4 Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173, 55216, Ingelheim, Germany

For all author emails, please log on.

Cardiovascular Diabetology 2013, 12:129  doi:10.1186/1475-2840-12-129

Published: 5 September 2013

Abstract

Background

Sulfonylureas (SUs) are commonly used in the treatment of type 2 diabetes (T2DM), usually as second-line treatment after the failure of metformin. However, SUs are associated with poor durability, hypoglycemia and weight gain. Empagliflozin is a sodium glucose cotransporter 2 (SGLT2) inhibitor in development for the treatment of T2DM. In Phase II/III trials, empagliflozin reduced hyperglycemia, body weight and blood pressure, with a low incidence of hypoglycemia. The aim of this Phase III study is to compare the effects of empagliflozin and the SU glimepiride as second-line therapy in patients with T2DM inadequately controlled with metformin immediate release (IR) and diet/exercise.

Method

After a 2-week placebo run-in, patients were randomized to receive empagliflozin 25 mg once daily (qd) or glimepiride 1–4 mg qd double-blind for 2 years, in addition to metformin IR. Patients who participate in the initial 2-year randomization period will be eligible for a 2-year double-blind extension. The primary endpoint is change from baseline in HbA1c. Secondary endpoints are change from baseline in body weight, the incidence of confirmed hypoglycemia and changes in systolic and diastolic blood pressure. Exploratory endpoints include markers of insulin secretion, body composition and responder analyses. Safety endpoints include the incidence of adverse events (AEs) (including macro- and microvascular adverse events) and changes from baseline in clinical laboratory parameters.

Results

Between August 2010 and June 2011, 1549 patients were randomized and 1545 patients were treated. At baseline, mean (SD) age was 55.9 (10.4) years, HbA1c was 7.92 (0.84)%, body mass index was 30.11 (5.59) kg/m2, systolic blood pressure was 133.5 (15.9) mmHg and diastolic blood pressure was 79.5 (9.4) mmHg.

Discussion

This is the largest study to compare the efficacy and safety of an SGLT2 inhibitor with an SU in patients with T2DM inadequately controlled on metformin to date. In addition to determining the effects of these treatments on glycemic control over the long term, this study will investigate effects on beta-cell function, cardiovascular risk factors and markers of renal function/damage. The results will help to inform the choice of second-line treatment in patients with T2DM who have failed on metformin.

Trial registration

Clinicaltrials.gov NCT01167881.

Keywords:
Blood pressure; Body weight; Empagliflozin; Glimepiride; Glycemic control; Macrovascular; Microvascular; SGLT2 inhibitor; Sulfonylurea; Type 2 diabetes