Combination of GLP-1 receptor agonists and SGLT2 inhibitors in cardiometabolic disease: synergistic, additive, or non-additive effects? A narrative review
Abstract
Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) are two novel classes of glucose-lowering agents with proven cardiometabolic benefits beyond glycaemic control. Both are now recommended in international guidelines for patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risk. As they operate through complementary mechanisms, their combined use may confer additive or synergistic benefits on cardiometabolic outcomes.
Aim: This narrative review examines and summarizes the available evidence on the synergistic effects of GLP-1 RAs and SGLT2 inhibitors in cardiometabolic disease, encompassing their effects on glycaemic control, body weight, blood pressure, cardiovascular events, renal outcomes, and mortality.
Methods: A narrative review of randomised clinical trials, observational studies, post-hoc analyses, and meta-analyses evaluating the combination of GLP-1 RAs and SGLT2 inhibitors in patients with T2DM was conducted. Individual drug class evidence from landmark cardiovascular and renal outcome trials is also reviewed to contextualise the potential for synergy. Evidence from trials conducted in non-diabetic populations with obesity or heart failure with preserved ejection fraction (HFpEF) is also examined where relevant to the combination therapy rationale.
Results: The combination of GLP-1 RAs and SGLT2 inhibitors consistently produced greater reductions in HbA1c (- 1.0 to -…
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