Combination SGLT2 inhibitor and GLP-1 receptor agonist therapy: a complementary approach to the treatment of type 2 diabetes

ABSTRACT

Among persons with type 2 diabetes (t2d), the development of glucose intolerance involves dysfunction in several organs and tissues, including the muscle, liver, pancreas, kidney, gastrointestinal tract, adipose tissue, and brain. individuals with t2d typically have a number of comorbidities, including hypertension, hyperlipidemia, and being overweight or obese, and are, consequently, at high cardiovascular risk. guidelines recommend a comprehensive care strategy that includes treatment of diabetes-related complications and comorbidities beyond those related to hyperglycemia. use of glucose-lowering therapies with complementary activities that address multiple facets of the disease may improve long-term outcomes for patients with t2d. two recent drug classes developed for use in t2d, glucagon-like peptide-1 receptor agonists (glp-1ras) and sodium glucose cotransporter 2 (sglt2) inhibitors, have been shown in clinical trials to have beneficial effects on glycemic control, body weight, cardiovascular risk factors, and (for liraglutide, semaglutide, and empagliflozin) cardiovascular outcomes, while having an acceptable safety profile. between them, these drug classes directly or indirectly affect many of the organs and tissues involved in the pathogenesis of t2d, and their beneficial effects on glycemic- and cardiovascular-related parameters are likely to be complementary and potentially additive. in the largest clinical trial of a glp-1ra and an sglt2 inhibitor in combination (duration-8), patients with t2d (n = 685) who received exenatide plus dapagliflozin added to their treatment regimen for 28 weeks had significantly greater reductions from baseline in glycated hemoglobin, body weight, and systolic blood pressure compared with patients who received either drug as monotherapy. this review summarizes the complementary aspects of these drug classes and presents the available data among patients receiving dual therapy with a glp-1ra and an sglt2 inhibitor.

KEYWORDS:

• Combination therapy
• complementary actions
• dual therapy
• GLP-1 receptor agonists
• SGLT2 inhibitors
• type 2 diabetes

Declaration of interest

R Busch is a member of the speakers’ bureau for AstraZeneca, Eli Lilly & Company, and Novo Nordisk. Sheridan Henness, PhD, on behalf of inScience Communications, Springer Healthcare, and Lisa Baker, PhD, CMPP, of inScience Communications, Springer Healthcare, provided medical writing support and this was funded by AstraZeneca. The authors have 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.

Additional information

Funding

This work was supported by AstraZeneca.