Novo Nordisk’s Ozempic has become the new poster child of the never-ending celebrity weight loss craze, quickly rising to the level of pop culture ubiquity that only a few prescription drugs have in the past. Its off-label use to curb appetite and shed pounds for otherwise healthy people has polarized the populace.
Ozempic, which is an injectable form of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, is approved in the U.S. for adults with Type 2 diabetes. Semaglutide is also the basis of the tablet form Rybelsus for diabetes and the injectable Wegovy for obesity — all sold by Novo.
The drugs’ presence in mainstream culture has prompted criticism that wealthy people looking to lose weight can gain access to the treatments while people with diabetes struggle. And European regulators are investigating reports that semaglutide is linked to suicidal thoughts.
But there is a lot of science behind the scenes of controversy and hype. Beyond diabetes and obesity, semaglutide is in development stages for a surprising list of diseases and conditions. Here’s a look at some of the other areas where the blockbuster is stirring up clinical and preclinical interest by researchers at Novo and other institutions.
Researchers have been studying the use of semaglutide in Alzheimer’s disease for more than two decades — beyond its role in gastrointestinal feedback, GLP-1 has been found to serve a function as a neuron protector that could potentially slow or reverse degenerative processes, according to a 2002 animal study from the National Institute on Aging.
Novo has continued that research in the clinic, with two phase 3 trials begun in 2021. The studies, called Evoke and Evoke+, compare semaglutide to a placebo in more than 1,800 patients with early Alzheimer’s and are expected to read out by 2026.
Neuroinflammation is thought to be one of the key contributors to Alzheimer’s as it causes neurons to lose their ability to communicate and eventually die, according to an article from Alzheimer’s Disease International, a nonprofit that partners with Novo. Semaglutide is thought to decrease levels of inflammation in the brain.
The particularly galling liver disease called nonalcoholic steatohepatitis (NASH) has stymied the research community for years. Intercept Pharmaceuticals, thought to be the leader in NASH drug development, dropped out of the arena last month, leaving a void to be filled by a bevy of other drug candidates — among them is semaglutide.
Novo is studying its workhorse GLP-1 in a phase 3 clinical trial that is expected to last about five years. But the company has already weathered a mid-stage failure in which patients did not show significant improvement compared to a placebo despite no new safety concerns. Still, it has indicated continued interest in studying semaglutide in NASH.
The company has also included semaglutide in a NASH drug cocktail along with Gilead Sciences in a mid-stage trial that began in 2021, continuing a partnership that survived a proof-of-concept study the year before.
Chronic kidney disease
Novo is also investigating semaglutide’s effect on chronic kidney disease in patients with Type 2 diabetes. In previous studies, the drug showed kidney-protective effects that were more pronounced in patients with preexisting chronic kidney disease, according to a 2021 study published in the American Heart Association journal Circulation.
Type 2 diabetes is considered a major risk factor for kidney disease, so positive results in further studies would go hand-in-hand with semaglutide’s current regulatory distinction.
Cystic fibrosis-related diabetes
The Cystic Fibrosis Foundation is collaborating with researchers from the University of Minnesota in a mid- to late-stage study to see whether semaglutide is an effective therapy alongside insulin for overweight or obese patients with cystic fibrosis-related diabetes. Diabetes is a common complication for patients with the disease and often requires intervention.
Canadian researchers are studying semaglutide as a treatment for complications associated with COVID-19. In particular, myocardial injury as a result of inflammation of the heart muscles could potentially be mitigated with the anti-inflammatory properties of semaglutide and other GLP-1 receptor agonists, the researchers posited. The study is listed as ongoing despite an expected end date in 2022.
Alcohol use disorder and addiction
In the same way that semaglutide has been shown to reduce appetite, researchers at Oklahoma State University are investigating its use as a means to control alcohol intake. The phase 2 study is expected to be completed in 2025. A study published in The Lancet in June showed that rats reduced alcohol intake and were less likely to relapse when dosed with semaglutide. There is also potential to curb other addictions like nicotine, gambling and other compulsive behaviors, according to a report from Scientific American.
An early-stage study being conducted at the Hospital of South West Jutland in Denmark hypothesizes that semaglutide could improve bone density in patients with a risk of fractures.