When semaglutide was first approved for type 2 diabetes in 2017, few anticipated that it would become one of the most consequential drugs of the twenty-first century. The weight loss results were remarkable. But it is what is happening beyond weight loss that is beginning to transform how researchers think about metabolic disease — and chronic disease more broadly.
The most significant development in recent years is the cardiovascular evidence. The SELECT trial, published in the New England Journal of Medicine in 2023, enrolled over 17,600 adults with obesity and established cardiovascular disease but without type 2 diabetes. After approximately three years, semaglutide reduced the risk of major cardiovascular events — heart attack, stroke and cardiovascular death — by 20%. This was not a weight loss effect alone: the cardiovascular benefit appeared earlier than the full weight loss effect, suggesting a direct anti-inflammatory action on blood vessels.
The kidney data is equally compelling. The FLOW trial, also published in 2024, showed that semaglutide reduced the risk of serious kidney disease progression by 24% in people with type 2 diabetes and chronic kidney disease. Regulators approved a new kidney disease indication on the basis of these results — a first for a GLP-1 medication.
Sleep apnoea is another frontier. The SURMOUNT-OSA trial demonstrated that tirzepatide reduced the severity of obstructive sleep apnoea by up to 63% in some patients — an effect comparable to CPAP therapy in magnitude. Researchers believe the mechanism involves both weight reduction around the airway and possible direct effects on upper airway muscle tone.
The most speculative — and most watched — area is neurodegeneration. GLP-1 receptors are found in the brain, particularly in regions associated with memory and inflammation. Several large trials are investigating whether semaglutide can slow the progression of Alzheimer’s disease and Parkinson’s disease. Early signals from epidemiological data are encouraging. Results from the first large randomised trials are expected in 2025 and 2026.
Sources
- Lincoff AM et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023;389:2221-2232. doi:10.1056/NEJMoa2307563
- Perkovic V et al. Semaglutide and Kidney Outcomes in Type 2 Diabetes and Chronic Kidney Disease (FLOW). N Engl J Med. 2024. doi:10.1056/NEJMoa2403347
- Malhotra A et al. Tirzepatide for Moderate-to-Severe Obstructive Sleep Apnea (SURMOUNT-OSA). N Engl J Med. 2024. doi:10.1056/NEJMoa2404881