New research has revealed that the combined use of sodium glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1-RAs) provides additional protection against heart and kidney diseases in diabetes patients. This study, published in The Lancet Diabetes & Endocrinology and presented at the 61st European Renal Association Congress in Stockholm, Sweden, underscores the benefits of these drugs beyond glucose control.
Mechanism of Action
SGLT2is, known as gliflozins, lower blood sugar by promoting its excretion through urine. On the other hand, GLP-1RAs, including drugs like Ozempic, enhance insulin release and sensitivity. Both drug classes have individually demonstrated improvements in cardiovascular outcomes. However, their combined impact on heart disease and kidney failure had remained unclear until now.
Study Insights
The SGLT2 Inhibitor Meta-analysis Cardio-Renal Trialists’ Consortium (SMART-C) conducted a comprehensive meta-analysis involving 12 large-scale, placebo-controlled trials of SGLT2is. The analysis included data from 73,238 diabetes patients, 3,065 of whom were also receiving GLP1-RAs. Findings indicated that SGLT2is provided cardiovascular and renal benefits regardless of GLP1-RA use.
SGLT2is reduced the risk of major adverse cardiovascular events, such as heart attacks, strokes, or cardiovascular death, by 11%. They also decreased the risk of hospitalization for heart failure or cardiovascular death by 23% and reduced the progression of chronic kidney disease by 33% when combined with GLP1-RAs. Additionally, the combination therapy slowed annual kidney function decline by nearly 60%. Importantly, no new safety issues were identified with the combined use of these medications.
Expert Commentary
Clinical Associate Professor Brendon Neuen, Senior Research Fellow at The George Institute for Global Health and Director of Kidney Trials at Sydney’s Royal North Shore Hospital, highlighted the significance of these findings. “Given the rapidly expanding indications for GLP-1 receptor agonists, examining their effects with SGLT2 inhibitors was crucial. This study is the largest and most comprehensive assessment of clinical outcomes for this drug combination.”
Neuen emphasized the independent protective effects of each drug class. “SGLT2 inhibitors offer clear protection against heart failure and chronic kidney disease, while GLP-1 receptor agonists can reduce the risk of heart attack, stroke, and kidney disease, as shown in the FLOW trial. Our results support using this combination to further enhance outcomes in type 2 diabetes patients who meet guideline recommendations for both therapies.
Implications for Diabetes Management
Diabetes is a major risk factor for cardiovascular and kidney diseases due to impaired glucose control, which damages blood vessels in these organs. Many diabetes patients suffer from cardiovascular disease or chronic kidney disease, with their prevalence increasing over time following a diabetes diagnosis.
SMART-C, co-chaired by A/Prof Brendon Neuen and Prof Hiddo Heerspink of The George Institute for Global Health, continues to explore the potential of combined therapies to improve the lives of diabetes patients. This study offers promising evidence for healthcare providers to consider dual therapy with SGLT2is and GLP1-RAs to enhance patient outcomes in managing diabetes-related complications.
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