Combination therapy with SGLT-2 inhibitors and GLP-1 receptor agonists as complementary agents that address multi-organ defects in type 2 diabetes

ABSTRACT

Type 2 diabetes (T2D) has a complex pathophysiology composed of multiple underlying defects that lead to impaired glucose homeostasis and the development of macrovascular and microvascular complications. Of the currently available glucose-lowering therapies, sodium–glucose cotransporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) both provide effective glycemic control and have been shown to reduce cardiovascular (CV) events in patients with T2D and a high CV risk or established CV disease. Because these agents have complementary mechanisms of action, they are able to act on multiple defects of T2D when used in combination. This review discusses the rationale for and potential benefits of SGLT-2i plus GLP-1RA combination therapy in patients with T2D. A search of the PubMed database was conducted for studies and reviews describing the combined use of SGLT-2is and GLP-1RAs, with a specific focus on identifying clinical studies of combination therapy in patients with T2D. In clinical studies, glycated hemoglobin (A1c) was significantly reduced over 28–52 weeks with SGLT-2i plus GLP-1RA therapy versus the individual agents or baseline. Several CV risk factors, including body weight, blood pressure, and lipid parameters, were also improved. SGLT-2i plus GLP-1RA therapy was generally well tolerated, with a low risk of hypoglycemia and no unexpected findings. Taken together with results from large CV outcomes trials of SGLT-2is and GLP-1RAs, combination therapy with these agents potentially provides effective durable glycemic control and CV benefits due to their complementary actions on the defects of T2D.

KEYWORDS:

• Cardiovascular risk
• combination therapy
• glucagon-like peptide-1 receptor agonists
• sodium–glucose cotransporter-2 inhibitors
• type 2 diabetes

Acknowledgments

Catherine Rees and Sarah Greig, PhD, of inScience Communications, Springer Healthcare (Auckland, New Zealand), provided medical writing support funded by AstraZeneca.

Declaration of interest

R Lajara has received consulting fees from and participated on speakers bureaus for AstraZeneca, Boehringer Ingelheim–Lilly, Novo Nordisk, Sanofi, and Valeritas.

Supplementary Materials

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Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

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Funding

The development of this manuscript was supported by AstraZeneca. A reviewer on this manuscript has disclosed that they are a regional, speaker for canagliflozin under sponsorship, by Janssen Pharmaceuticals. The other peer reviewers on the manuscript have no other relevant financial relationships or otherwise to disclose.