Brendon Neuen, MBBS, PhD: Optimizing Cardiorenal Prognosis with GLP-1, SGLT2 Combination

The combined use of sodium-glucose transport protein 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists may offer notable benefits for optimizing cardiovascular and renal outcomes in patients with diabetes, according to findings from a collaborative meta-analysis of trials from the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium (SMART-C).

A total of 12 SMART-C trials encompassing more than 70,000 patients with diabetes were assessed to evaluate the benefits of SGLT2 inhibitors with and without the use of GLP-1 receptor agonists, with results demonstrating consistent positive impacts on major adverse cardiovascular events, hospitalization for heart failure or cardiovascular death, chronic kidney disease progression, and the occurrence of adverse events with the combined use of SGLT2 inhibitors and GLP-1 receptor agonists.

Type 2 diabetes treatment guidelines and society recommendations endorse the use of SGLT2 inhibitors, GLP-1 receptor agonists, or both for individuals with type 2 diabetes with or at a high risk of atherosclerotic cardiovascular disease. However, the combined use of both classes of agents has not yet been explored in any trial sufficiently powered to examine the effects of SGLT2 inhibitors on clinical outcomes in patients receiving or not receiving GLP-1 receptor agonists.

“The guidelines are recognizing that there is a potential to improve outcomes with combination use of SGLT2 and GLP-1 together, but that is based largely on the fact that these drugs have different mechanisms of action,” Brendon Neuen, MBBS, PhD, said to HCPLive, explaining how although small, short trials have demonstrated benefits with combination SGLT2/GLP-1 receptor agonist therapy, current clinical trial data is not sufficient to evaluate the effects of SGLT2 with or without GLP-1 receptor agonists because these trials began before the benefits of either class were confirmed.

He and a group of researchers from the SMART-C team leveraged data from 12 trials included in the consortium encompassing 73,238 patients, 3065 of whom were using GLP-1 receptor agonists at baseline, to evaluate the effects of SGLT2 inhibitors on cardiovascular, kidney, and safety outcomes by background use of GLP-1 receptor agonists.

Results showed an 11% reduction in MACE, a 23% reduction in hospitalization for heart failure or cardiovascular death, and a 37% reduction in kidney disease progression, defined as 40% decline in GFR, kidney failure, or death due to kidney disease. Treatment effects were consistent regardless of background GLP-1 receptor agonist use and similar findings were observed with analysis of GFR slopes.

“That information probably provides the strongest and clearest evidence yet that these drugs have independent and additive effects, and should be used in combination to further optimize cardiorenal prognosis,” Neuen said.

Looking ahead, Neuen indicated he believes the role of combination therapy is going to be “so important” because no 1 or 2 drugs are going to improve the loss of kidney function and reduce the risk of cardiovascular complications in high-risk patients, therefore necessitating a multi-medicine approach in which the intensity of treatment is matched to patients’ risk.

Reference

^{Brooks, A. SGLT2 Inhibitor, GLP-1 RA Combination Improves Cardiovascular, Kidney Outcomes in Diabetes. HCPLive. July 9, 2024. Accessed July 12, 2024. https://www.hcplive.com/view/sglt2-inhibitor-glp-1-ra-combination-improves-cardiovascular-kidney-outcomes-diabetes}