GLP-1-based therapeutics for cardiorenal protection in metabolic diseases

Jun 25, 2025Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

GLP-1 Treatments for Protecting Heart and Kidney Health in Metabolic Diseases

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Abstract

Semaglutide has been shown to reduce body weight by up to 15% in individuals with obesity but without type 2 diabetes.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) consistently lower HbA1c levels and body weight in both clinical and real-world settings.
Evidence suggests that GLP-1RAs provide cardiorenal benefits beyond glycemic control in certain high-risk populations.
In patients with type 2 diabetes, GLP-1RAs improve both cardiovascular and relevant kidney outcomes.
Next-generation GLP-1-based therapeutics, such as tirzepatide, which targets multiple hormone receptors, may enhance weight loss and metabolic efficacy.
Tirzepatide has shown up to 22.5% weight loss in phase-3 trials for managing both type 2 diabetes and obesity.

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Over last decade, significant progress has been made in cardiorenal protection for metabolic diseases, such as type 2 diabetes (T2D) and obesity. With an expanding range of pharmacological options and continuously evolving guidelines, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have garnered substantial clinical and societal attention for their role in T2D and weight-management. GLP-1RAs have consistently demonstrated robust HbA1c- and bodyweight-reducing efficacy in clinical and real-world studies. In addition, mounting data established their cardiorenal benefits beyond glycemic control in select high-risk populations. In T2D, GLP-1RAs have been shown to improve both hard cardiovascular and, more recently, relevant kidney outcomes. Meanwhile, in individuals with obesity but without T2D, semaglutide (at a higher dose compared to T2D) reduces body-weight by up to 15%, and lowers the risk of major adverse cardiovascular-events by 20%. The success of GLP-1-based therapy fueled the development of new single-molecules, that combine GLP-1R agonism with activation of other entero-pancreatic hormone receptors (e.g. glucose-dependent insulinoptropic polypeptide [GIP], glucagon and amylin) aiming to achieve complementary and potentially synergistic effects. These next-generation GLP-1-based therapeutics for metabolic diseases, either already available or approaching clinical approval, appear to enhance the metabolic and weight-reducing efficacy compared to existing GLP-1RAs. An example is tirzepatide, a dual GLP-1/GIP receptor agonist, which has been approved for both T2D and obesity-management, demonstrating up to 22.5% weight-loss in phase-3 trials. This review explores the landscape of current and emerging GLP-1-based therapies, their efficacy in managing hyperglycemia and bodyweight, recent evidence supporting their cardiorenal benefits, and clinical implications of these advancements.

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GLP-1-based therapeutics for cardiorenal protection in metabolic diseases

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