Sodium–glucose cotransporter-2 inhibitor combination therapy to optimize glycemic control and tolerability in patients with type 2 diabetes: focus on dapagliflozin–metformin

Abstract

In type 2 diabetes (T2D), early combination therapy using agents that target a number of the underlying pathophysiologic defects contributing to hyperglycemia may improve patient outcomes. For many patients, the combination of metformin with a sodium–glucose cotransporter-2 (SGLT-2) inhibitor may be a good option because these agents have complementary mechanisms of action, neutral-to-positive effects on body weight, and a low risk of hypoglycemia. This review focuses on the combination of metformin with dapagliflozin, a member of the SGLT-2 inhibitor class of antidiabetes agents. In clinical trials, the combination of dapagliflozin with metformin produced significant and sustained reductions in glycated hemoglobin and body weight in a broad range of adult patients with T2D, including those initiating pharmacotherapy and those with more advanced disease. These reductions were accompanied by modest decreases in blood pressure. Dapagliflozin as add-on therapy to metformin was well tolerated and associated with low rates of hypoglycemia. Genital infections and, in some studies, urinary tract infections were more frequent with dapagliflozin than with placebo. Early combination therapy with dapagliflozin and metformin may be a safe and appropriate treatment option that enables patients with T2D to achieve individualized glycemic goals as either initial combination therapy in treatment-naïve patients or as dapagliflozin add-on in patients inadequately controlled with metformin therapy.

Keywords:

• combination therapy
• dapagliflozin
• metformin

Acknowledgments

Medical writing support for the preparation of this manuscript was provided by Richard Edwards, PhD, and Janet Matsuura, PhD, from Complete Healthcare Communications, LLC (Chadds Ford, PA), with funding from AstraZeneca.

Disclosure

SS has served as an advisory board member for Janssen, Merck, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Salix, Novo Nordisk, Takeda, and Genesis Biotechnology Group and on the speakers bureaus of Takeda, Janssen, Merck, Novo Nordisk, Salix, Boehringer Ingelheim, Eli Lilly, Eisai, AstraZeneca, GlaxoSmithKline, and Amgen. AK was an employee of AstraZeneca during the development of this manuscript. The authors report no other conflicts of interest in this work.