How Mass General Brigham Researchers Are Working to Advance Our Understanding of GLP-1 Medications
You may have heard a lot about GLP-1 medications in the news, but did you know the research that led to development of these drugs originated right here at Mass General Brigham?
Next month, Massachusetts General Hospital will present the 2025 Warren Triennial Prize to four investigators (including two Mass General alumni) who made fundamental discoveries during the 1980s and 1990s that led to the development of GLP-1 agonist medications such as semaglutide (sold as Wegovy for weight loss and Ozempic/Rybelsus for diabetes).
Today, researchers across Mass General Brigham are continuing to advance our understanding of these GLP-1 agonists and conducting new studies to learn more about the health benefits and side effects of these drugs. Here are some examples:
Study Shows GLP-1 Medication Reduces Risk of Death from Heart Disease
A large clinical trial that included investigators at Brigham and Women’s Hospital (BWH) has demonstrated that semaglutide, a GLP-1 agonist medication approved to treat diabetes and weight loss, has another major benefit — reducing the incidence of major cardiovascular events among those with overweight or obesity but not diabetes.
The SELECT trial took place at 804 clinical sites in 41 different countries, including BWH. The double-blinded, randomized study included 17,000 patients, all 45 years or older with a history of heart disease and overweight or obesity, but none had diabetes. Half received weekly semaglutide injections while half received the placebo.
Researchers found that patients who received weekly semaglutide injections had a significant decrease in major heart disease events (heart attacks, strokes and death) compared to the placebo group. The patients who took semaglutide also lost significantly more weight and had a greater decrease in blood pressure and indications of cardiovascular disease risk.
“Obesity and overweight are risk factors for worse outcomes from respiratory diseases like COVID and cardiovascular conditions such as heart attack and stroke,” said Benjamin Scirica, MD, a Mass General Brigham cardiologist and lead author of the study. “Semaglutide is often thought of first as a weight loss drug, but data from this study and others highlight the fact that it also improves overall cardiovascular risk and lowers the risk of non-cardiovascular events.”
Use of GLP-1 Medications to Treat Obesity More than Doubled from 2022 to 2023
A recent study by researchers at BWH and colleagues examined a large sample of privately insured patients with obesity and found the use of GLP-1 agonists to treat obesity more than doubled from 2022 to 2023.
During the same period, there was a 25.6% decrease in patients undergoing metabolic bariatric surgery to treat obesity. The study was published in JAMA Network Open.
“Our study provides one of the first national estimates of the decline in utilization of bariatric metabolic surgery among privately insured patients corresponding to the rising use of blockbuster GLP-1 RA drugs,” said senior author Thomas C. Tsai, MD, MPH, a metabolic bariatric surgeon in the Department of Surgery at BWH.
“For now, metabolic bariatric surgery remains the most effective and durable treatment for obesity,” Tsai added. “National efforts should focus on improving access to obesity treatment — whether pharmacologic or surgical — to ensure patients can receive optimal care.”
Study Finds an Association Between Semaglutide Use and an Uncommon Blinding Condition
While Mass General Brigham researchers continue to investigate the benefits of taking GLP-1 medications, they are also looking into the potential drawbacks of taking these drugs. Researchers from Mass Eye and Ear and colleagues conducted a retrospective study of 16,827 patients who were evaluated by neuro-ophthalmologists.
The investigators were looking for an association between semaglutide treatment and a condition called nonarteritic anterior ischemic optic neuropathy (NAION), which is a loss of blood flow to the optic nerve that can lead to sudden blindness.
Among the patients in the cohort review, 710 had type 2 diabetes (T2D) and 979 were overweight or obese. Among the patients with T2D, the researchers identified 17 NAION events in those taking semaglutide, compared to six events in T2D patients taking non-GLP-1 medications.
Among the patients who were overweight or obese, the researchers identified 20 NAION events in patients taking GLP-1 medications compared to three incidents among patients receiving non GLP-1 treatments.
The cumulative incidence of NAION for patients treated with semaglutide was 6.7% vs. 0.8% in the non GLP-1 group, so the overall risk to patients in both treatment groups is low. More research is needed to understand what’s driving this association.
“To be perfectly clear, I would not take my findings and use them to recommend that patients stop taking their medications,” said Joseph Rizzo, MD, Director of the Neuro-Ophthalmology Service at Mass Eye and Ear and the senior author of the study. “Our finding was really the first possible significant negative finding with these drugs. It may just merit extra caution in the consideration between doctors and patients about who may use this medicine.”