One of Dr Mo Sarhan’s patients was experiencing intense cravings for opioids and alcohol when the Florida-based doctor offered him a striking solution: the Eli Lilly weight-loss drug Mounjaro.
“Within days, all of his cravings were gone and he was much more effective in his engagement and treatment. He’s done great since,” Sarhan says.
Sarhan and his colleague Steven Klein at the Caron Treatment Centers in Florida and Pennsylvania have prescribed a range of so-called glucagon-like peptide-1 receptor agonists (GLP-1s) to treat addictions, using them alongside traditional therapies, to around 75 patients.
The results, which Sarhan describes as “compelling”, are the latest sign that drugs such as Mounjaro, Ozempic and Wegovy could be effective treatments for a startlingly wide range of conditions well beyond their original focus on obesity and diabetes.
On Tuesday, Dave Ricks, Eli Lilly’s chief executive, said the company would begin large studies of GLP-1s in alcohol, nicotine and drug abuse — the first pharmaceutical group to do so.
“These medicines, we think and we’ve aimed to prove, can be useful for other things we don’t think about connected to weight,” he told the Economic Club of Washington DC.
While GLP-1s are not clinically approved for addiction treatment, preliminary studies suggest they reduce cravings by acting on pleasure pathways in the brain — similar to the mechanism that dampens appetite.
In recent years, GLP-1s have helped transform the waistlines of patients and the top lines of pharmaceutical groups Novo Nordisk and Eli Lilly. Worldwide, more than 1bn people are defined as obese, according to research published this year in The Lancet, with rates doubling for adults and quadrupling for children and adolescents between 1990 and 2022. Conditions linked to obesity, such as chronic kidney disease and diabetes, are increasingly prevalent too.
According to data provider Airfinity, there are 66 ongoing, late-stage trials of GLP-1 drugs for obesity, diabetes and a range of other conditions linked to excess weight. The prospect of broader uses for the drugs is one reason that Goldman Sachs analysts anticipate a $130bn market for them by 2030.
But there are also ongoing studies in treatment areas with few apparent links to excess weight. Novo Nordisk is running three late-stage trials of semaglutide, the active ingredient in its Ozempic and Wegovy drugs, for Alzheimer’s disease. Another of the class of drugs, lixisenatide, has shown some early promise in slowing the worsening of motor symptoms in Parkinson’s disease patients.
Widespread uptake of the drugs could help tackle the rising tide of chronic diseases across the world and lower the costs associated with them for health systems.
In one example, Airfinity estimates that Wegovy could prevent up to 3.8mn cases of obstructive sleep apnoea, a breathing disorder, in the US by 2030. That could cut expenditure on the CPAP (continuous positive airway pressure) machines used to help patients manage symptoms in the US by up to $3bn.
Sarhan’s patients, most of whom pay for the drug themselves and are all informed beforehand of its regulatory status, have taken the treatments for addiction to nicotine, inhalants and alcohol. But the therapeutic mechanisms of the drugs are not yet fully understood and many of the benefits have not been verified in late-stage trials.
Production of GLP-1s is currently dominated by Novo Nordisk and Eli Lilly, which have much more incentive to maximise the revenue potential of the obesity market than to spend on experimental clinical trials in unproven treatment areas.
And the hefty price tags and unpleasant side effects associated with current weight-loss treatments mean they are not yet a panacea for the growing body of chronic health conditions across the world.
Lower-priced, more widely available drugs that could be taken orally are “the direction of travel,” says Naveed Sattar, professor at the University of Glasgow and chair of the UK government’s obesity mission. “But we are not there yet — because the drugs are too expensive.”
GLP-1 receptor agonists have surprised scientists before. The gut hormone was originally discovered in the 1980s, but found to break down quickly in the body. It was not until researchers discovered a similar but more stable compound in the venom of the Gila monster, a lizard native to North America, that they were able to produce long-lasting drugs mimicking GLP-1’s effects. The first GLP-1 based drug was approved in 2005.
Early GLP-1s were developed as diabetes treatments owing to their ability to stimulate insulin production, with weight loss initially a useful side effect. Previous treatments for obesity itself came with dangerous side effects. The “fen-phen” cocktail of an appetite suppressant and amphetamine was withdrawn in 1997 after its use was linked to heart valve defects.
Rather than increasing cardiovascular risk, GLP-1s have shown impressive benefits. Last year, Novo Nordisk unveiled data that suggested semaglutide cut the risk of heart attacks by 28 per cent in its so-called Step trial of 17,604 patients, and reduced the risk of death by 18 per cent.
The results of the trial have helped expand the drugs’ usage. In March, Novo Nordisk secured US approval for Wegovy to reduce the risk of heart attacks and strokes in overweight or obese adults with cardiovascular disease.
“It’s a complete turnaround from what we’ve had before,” says Vlado Perkovic, a renal specialist at UNSW Sydney, who has done research on the impact of GLP-1s on kidney conditions. Trials show the drugs are effective in treating both chronic kidney disease and metabolic dysfunction-associated steatohepatitis or Mash, a liver disease.
Meanwhile, Eli Lilly’s Mounjaro has slashed the severity of sleep apnoea, a breathing disorder, by nearly two-thirds and cut heart failure outcomes in a separate trial.
Sattar, the University of Glasgow professor, says weight loss alone is a major driver of improvements across each of these disease areas.
“The weight loss attributes of the drugs are responsible for most of the benefits in multiple diseases, or are the predominant reason why these drugs affect multiple diseases,” he says.
As new and stronger drugs emerge, these effects are likely to increase. Novo Nordisk’s chief executive Lars Fruergaard Jørgensen said last month he was “very excited” about the potential of the company’s new CagriSema drug on diseases linked to obesity. Upcoming data is expected to show the drug delivers 25 per cent weight loss on average, an increase from the 22 per cent attributed to Mounjaro.
Additional reporting by Oliver Barnes in New York
