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ABSTRACT
Type 2 diabetes mellitus is a progressive disease with multiple underlying pathophysiologic defects. Monotherapy alone cannot maintain glycemic control and leads to treatment failure. Ideally, a combination of glucose-lowering agents should have complementary mechanisms of action that address multiple pathophysiologic pathways, can be used at all stages of the disease, and be generally well tolerated with no increased risk of hypoglycemia, cardiovascular events, or weight gain. The combination should also provide conveniences for patients, such as oral dosing, single-pill formulations, and once-daily administration, potentially translating to improved adherence. Two classes of glucose-lowering agents that meet these criteria are the sodium glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. This article reviews the rationale for combination therapy with these agents, and evidence from clinical trials with empagliflozin and linagliptin or dapagliflozin and saxagliptin in the management of type 2 diabetes mellitus. Both combinations have been approved as single-pill formulations.
Declaration of interest
The author meets criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). Writing support was provided by Daniella Babu, PhD, of Envision Scientific Solutions, which was contracted and funded by BIPI. BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.