GLP-1 receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits

Jan 17, 2026Lancet (London, England)

Metabolic, heart, and kidney benefits of glucagon-like receptor activators and new incretin medicines

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Abstract

GLP-1 receptor agonists are highly effective for glycaemic control and bodyweight reduction.

These medications are associated with a low risk of hypoglycaemia.
They may reduce the risks of major cardiovascular events, including non-fatal heart attacks and strokes.
GLP-1 receptor agonists could slow the decline in kidney function and reduce albuminuria, potentially delaying kidney failure.
Clinical trials indicate benefits for obesity-related conditions, including prevention of type 2 diabetes and improvements in heart failure and liver disease.
Emerging research is exploring novel uses for these drugs in neurodegenerative diseases and substance use disorders.
Combination therapies activating multiple receptors may offer greater efficacy, particularly for weight loss, though gastrointestinal side effects remain a concern.

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GLP-1 receptor agonists were initially developed to treat type 2 diabetes and have had a transformative effect on its therapy, and are highly effective for glycaemic control, with the added benefit of bodyweight reduction and a low risk of causing hypoglycaemia. GLP-1 receptor agonists reduce risks for major adverse cardiovascular events (eg, non-fatal myocardial infarction, stroke, and cardiovascular death), and the risk of admission to or treatment within hospital for heart failure. These drugs reduce albuminuria and slow the decline in estimated glomerular filtration rate over time, therefore delaying or preventing kidney failure. Furthermore, GLP-1 receptor agonists (eg, liraglutide and semaglutide) and the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor co-agonist tirzepatide have been approved for treatment of obesity, with clinical trials establishing benefits for various obesity-related conditions: prevention of type 2 diabetes; risk for major adverse cardiovascular events; heart failure, especially with preserved ejection fraction; regression of steatosis and prevention of fibrosis in steatotic liver disease; and symptomatic improvements in obstructive sleep apnoea and knee osteoarthritis. Current developments include the exploration of novel indications (eg, neurodegenerative diseases and substance use disorders) with suggestive evidence of efficacy, and the development of small-molecule GLP-1 receptor agonists for oral treatment to improve convenience. Dual (ie, GLP-1-glucagon and GLP-1-amylin) and triple (ie, GIP-GLP-1-glucagon) receptor agonists activating multiple receptors promise greater efficacy than mono-agonists, especially for weight loss. However, some clinical development programmes have a high burden of adverse gastrointestinal events, and dose-escalation regimens should be optimised to reach acceptable tolerability.

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GLP-1 receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits

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