Largest diabetes study reveals major benefits of SGLT2 inhibitors and GLP1 receptor agonists dual therapy

Pharma News: Combined use of sodium glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1-RAs) is likely to offer additional protection against heart and kidney disease in patients with diabetes.

Clinical Associate Professor Brendon Neuen, Senior Research Fellow at The George Institute for Global Health, Director of Kidney Trials at Sydney’s Royal North Shore Hospital, and lead author on the paper, said, “Given the rapidly expanding indications for the use of GLP-1 receptor agonists, it was important to look at their effects with SGLT2 inhibitors. This study represents the largest and most comprehensive assessment of clinical outcomes for this combination of medicines.”

SGLT2 inhibitors include AstraZeneca’s Forxiga (dapagliflozin), Boehringer Ingelheim’s Jardiance (empagliflozin) and Novartis’ Entresto (sacubitril-valsartan).

As a part of the SGLT2 Inhibitor Meta-analysis Cardio-Renal Trialists’ Consortium (SMART-C), researchers pooled data across 12 large-scale, placebo-controlled trials of SGLT2is and involving 73,238 patients with diabetes, 3065 of whom were already receiving GLP1-RAs. The meta-analysis showed that the benefits of SGLT2is were observed independent of GLP1-RA use.

SGLT2is reduced the risk of major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death) by 11% and hospitalisation for heart failure or cardiovascular death by 23% versus placebo, even when added to GLP1-RAs.

It also reduced the risk of chronic kidney disease progression by 33% when added to GLP1-RAs and slowed the annual loss of kidney function by almost 60% when added to GLP-1RAs. No new safety concerns were identified when SGLT2is and GLP-1RAs were used in combination.

Associate Professor Neuen said that both classes of medicines work independently of each other.

“SGLT2 inhibitors have clear protective effects against heart failure and chronic kidney disease, while GLP-1 receptor agonists can reduce the risk of heart attack, stroke and also kidney disease – as recently demonstrated in the landmark FLOW trial.

“Our findings support using this combination to further improve outcomes in patients with type 2 diabetes who meet guideline recommendations for both therapies,” he emphasised.

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