The combination of sodium glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1-RAs) may offer additional protection against heart and kidney disease in patients with diabetes.1According to the latest research: The Lancet Diabetes and Endocrinology.
SGLT2, also known as gliflozins, are a class of medications that lower blood sugar levels by increasing their excretion in the urine, while GLP-1RAs such as Ozempic work by increasing insulin release and sensitivity. Both medications have been shown to improve cardiovascular outcomes.
Small, relatively short-term studies suggest that combining these drugs improves blood sugar control, but the combined effect on heart disease and kidney failure is unclear.
As part of the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trials Consortium (SMART-C), researchers pooled data from 12 large placebo-controlled trials of SGLT2 inhibitors in 73,238 patients with diabetes, 3,065 of whom were already taking a GLP1-RA. The meta-analysis showed that the benefits of SGLT2 inhibitors were observed independent of GLP1-RA use.
SGLT2is, when added to GLP1-RAs, reduced the risk of major cardiovascular events (myocardial infarction, stroke, or cardiovascular death) by 11% and reduced hospitalization for heart failure or cardiovascular death by 23% compared to placebo. They also reduced the risk of chronic kidney disease progression by 33% when added to GLP1-RAs and slowed the annual decline in kidney function by almost 60% when added to GLP-1RAs. No new safety concerns were identified when SGLT2is were used in combination with GLP-1RAs.
“Given the rapidly expanding indications for use of GLP-1 receptor agonists, it was important to investigate their effect when combined with an SGLT2 inhibitor. This study represents the largest and most comprehensive evaluation of the clinical outcomes of this drug combination,” said Clinical Associate Professor Brendon Nguyen, Senior Investigator at the George Institute for Global Health and Director of Renal Trials at Royal North Shore Hospital, Sydney, and lead author on the paper.
Nguyen said both classes of drugs work independently of each other: “SGLT2 inhibitors have clear preventive effects against heart failure and chronic kidney disease, while GLP-1 receptor agonists can reduce the risk of heart attack, stroke and even kidney disease, as recently demonstrated in the landmark FLOW trial.”2 Our findings support that this combination therapy further improves outcomes for patients with type 2 diabetes who meet guideline recommendations for both treatments.”
Diabetes is a known risk factor for cardiovascular and kidney disease, with impaired blood sugar control damaging blood vessels in the heart and kidneys. Many people with diabetes live with cardiovascular and chronic kidney disease, the prevalence of which increases in the years after diabetes is diagnosed.3
SMART-C is co-chaired by Nguyen and Professor Hido Hairspink from the George Institute for Global Health.
1. Apperloo E, Neuen BL et al. Efficacy and safety of sodium glucose cotransporter 2 inhibitors with or without glucagon-like peptide-1 receptor agonists: a SMART-C collaborative meta-analysis of randomized controlled trials. The Lancet. 2024. https://doi.org/10.1016/S2213-8587(24)00183-9
2. Perkovic V, et al. Effect of semaglutide on chronic kidney disease in patients with type 2 diabetes. NEJM. 2024. https://doi.org/10.1056/NEJMoa2403347
3. Pearson-Stuttard J, et al. Variation in comorbidity burden over disease duration in patients with type 2 diabetes: a population-based analysis of real-world evidence. EClinicalMedicine. 2022. https://doi.org/10.1016/j.eclinm.2022.101584
