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Study shows, for the first time, that combining two effective medications for type 2 diabetes can result in further reductions of cardiovascular and renal events

A population-based cohort study finds that the GLP-1 RA–SGLT-2 inhibitor combination is associated with a 30% reduction in the risk of cardiovascular and renal events compared with either medication class alone.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which include Ozempic®, Rybelsus® and other widely-used drugs, and sodium-glucose cotransporter (SGLT)-2 inhibitors, such as Brenzavvy™, Invokana®, Farxiga®, Jardiance® and Steglatro®, have been shown to be effective treatments in type 2 diabetes, with large randomized controlled trials demonstrating cardiovascular and renal benefits. But what happens if, as is increasingly the case, patients with type 2 diabetes take both medication classes at the same time, in combination?

In a just published study in the BMJ, a research team from the Lady Davis Institute for Medical Research (LDI) at the Jewish General Hospital addressed this question made vital by the growing popularity and increasing use of this treatment regimen by patients with type 2 diabetes. “We conducted the first real-world study to assess whether the combined use of GLP-1 RAs and SGLT-2 inhibitors is associated with a decreased risk of major adverse cardiovascular events (MACE) and serious renal events, separately, compared to the use of either drug class alone,” says Professor Laurent Azoulay, Senior investigator in the Centre for Clinical Epidemiology of the LDI, who led the study. “Previous observational studies did not use either drug class alone as the comparator.”

Using the United Kingdom Clinical Practice Research Datalink, which was linked to hospital and vital statistics databases, and a prevalent new-user design, the study matched patients initiating a GLP-1 RA–SGLT-2 inhibitor combination with patients continuing their GLP-1 RA or SGLT2 inhibitor treatment alone.

Overall, the findings indicate the GLP-1 RA-SGLT-2 inhibitor combination is associated with a 30% reduction in the risk of cardiovascular and renal events compared with either medication class alone. As this combination is increasingly used among patients with type 2 diabetes, the results highlight a potentially beneficial treatment strategy for managing type 2 diabetes and mitigating cardiovascular and renal risks.

“The results of our study have the potential to inform treatment guidelines for type 2 diabetes and guide the treatment of those at an increased risk of cardiovascular and adverse renal events”, says Professor Azoulay. “In particular, this information can help physicians decide if their patients on a GLP-1 RA or SGLT-2 inhibitor would benefit from combination treatment.”

Simms-Williams N, Treves N, Yin H, Lu S, Yu O, Pradhan R, Renoux C, Suissa S, Azoulay L. Combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors on the incidence of cardiovascular and serious renal events: population-based cohort study. BMJ 2024;385:e078242.