Now that GLP-1 drugs have revolutionized how millions of Americans treat obesity and Type 2 diabetes, scientists are exploring the benefits of using the drugs for a host of other chronic diseases — many with few treatment options — such as heart failure, chronic liver disease, obstructive sleep apnea, and even substance use disorders.

“Their role is now being understood to be much, much more fundamental to human health, and to promoting longevity and preventing chronic illness progression,” said Muthiah Vaduganathan, a cardiologist at Brigham and Women’s Hospital and faculty at Harvard Medical School.

GLP-1 receptor agonists — sold under brand names like Ozempic and Mounjaro — were initially developed to treat diabetes. But instead of addressing biomarkers linked to certain disease outcomes, these drugs influence the central cardio-kidney metabolic process, Vaduganathan said. This overarching approach has made GLP-1 drugs the most effective and tolerable choice for most patients treating diabetes and obesity. It’s also what makes it likely that they influence a number of closely related diseases.

“Excess weight and adiposity and obesity are the fundamental drivers of why these conditions are not only occurring but also progressing over time,” said Vaduganathan. “And so that reframing has allowed us now to rapidly target those fundamental drivers of adiposity with really effective and safe therapies like GLP-1 receptor agonists.”

‘That’s something you don’t see for every drug’

Nils Krüger, an instructor at Harvard Medical School and Brigham and Women’s Hospital, has investigated a wide range of positive effects for GLP-1 drugs in clinical practice. In a recent study, he and his team found that GLP-1s were highly effective for patients with heart failure with preserved ejection fraction, in which the heart’s muscle becomes so stiff that the ventricle holds less blood than usual; the GLP-1s showed a 40 percent relative risk reduction compared to older diabetes medication. “That’s something you don’t see for every drug,” Krüger said.

Like Vaduganathan, he believes it’s largely because GLP-1 drugs lower excess fat in the body, which drives the disease. “It’s just astonishing how many indications those medications seem to be effective for or have some beneficial effects,” Krüger said.

Josephine Li, the clinical director of the Diabetes Center at MGH and assistant professor at Harvard Medical School, also finds GLP-1s more broadly effective than previous generations of diabetes drugs. “There were older diabetes medications where there were issues with increased risk of heart failure,” Li said. With GLP-1 drugs, “What was surprising and amazing was they were found to reduce the risk of major adverse cardiovascular events like cardiovascular death, nonfatal myocardial infarction, nonfatal stroke. And this has been shown over and over with different GLP-1s within the class.”

‘Revolutionary for patients’

These combined benefits have changed the way Vaduganathan and Li practice medicine. “When I initially completed medical training, everyone in practice recognized the major role of obesity,” said Vaduganathan, “but our tool kit was so limited in terms of effective options to actually address this issue.” GLP-1 drugs have made treatment more palatable — and effective — for patients who might have otherwise elected for bariatric surgery.

For Li, the options for treating diabetes just years ago were similarly narrow. “It was a couple of oral meds and then it’s like, ‘Too bad, you have to start insulin,’” she recalled. Now, there are far more options, with new oral GLP-1 drugs and oral incretin drugs that are being evaluated in clinical trials. “It really changes the treatment landscape,” she said. “You don’t have to be doing an injection multiple times a day. From a delivery perspective, that’s been revolutionary for patients.”

Doctors still run into issues prescribing GLP-1s. The FDA has approved them to treat Type 2 diabetes and obesity, but many conditions, including Type 1 diabetes, lack approval. Insurance companies sometimes reject claims for alternative uses of GLP-1 drugs, which are expensive, even for patients who are overweight or obese.

Other demographic groups have been understudied in clinical trials so far, Li said, including pregnant women, children, and people who are suffering from advanced kidney disease or who are on dialysis. “These are people who are typically excluded from the trials, but they’re patients we take care of,” Li said, “so it’s just thinking about these subpopulations and whether the drugs can be safely used and how to modify how you use them.”

Despite these limitations, doctors said that these drugs have increased communication between healthcare professionals across specialties. “Because we are using these therapies together, individual clinicians may be prescribing them, but other clinicians may be adjusting them,” said Vaduganathan. “A positive effect of these therapies has actually been on the structure of healthcare delivery for complex conditions.”

Li agreed. “I find myself in my practice reaching out to someone’s cardiologist, reaching out to someone’s nephrologist, getting someone seen by a dietitian,” she said. She also finds herself having a lot of conversations with other physicians, thinking through potential safety concerns and side effects of the medicines. Over the past few years, doctors have seen an increase in reports of pulmonary aspiration during procedures, for instance, because GLP-1 drugs slow digestion.

Promise treating addiction

This communication spans specialties beyond what one might expect for GLP-1 drugs. Mary Shen, a resident physician at Brigham and Women’s Hospital who studies substance use disorders, said that studies have shown a growing relationship between GLP-1 drugs and addiction. “It started because, anecdotally, physicians were starting to see that their patients were reporting, ‘Oh, I haven’t smoked in a while,’ and ‘Oh, I haven’t had alcohol in a while.’”

The results spurred case reports, which led to preclinical studies and mouse models — with often promising results. “In the past few years, there’s been a huge increase in studies examining GLP-1s and substance use disorder,” Shen said.

In 2024, she said, researchers conducted a review of five clinical trials for GLP-1 drugs related to substance use disorder. That year, she and her mentor, Joji Suzuki, director of Brigham and Women’s Hospital’s Division of Addiction Psychiatry, found that given the small number of studies, there was not yet enough data to recommend GLP-1 agonist drugs across tobacco, alcohol, and cocaine use disorders. Kwadwo Owusu-Boaitey and Laura Holsen were co-authors of that study.

A year later, Shen said, the landscape is changing. Although the use of GLP-1s has not been approved by the FDA to treat substance use disorders, there are more than 15 clinical trials in progress globally. The Suzuki lab is also running two clinical trials, one for opioid use disorder and one for alcohol use disorder.

“We’re still exploring what formulations are most useful, what conditions they’re most useful for, and which patients they’re the most effective in,” said Shen. “But it does look like there’s some promising evidence.”

Shen said the same mechanism that modulates pathways in the gut and the pancreas also affects the brain. “We see addiction is closely tied to the reward systems in the brain and now we know that GLP-1 receptors are also found in the same brain structures,” said Shen. “By targeting this, it may help regulate some of the responses to these substances.”

Researchers acknowledge that there is still much work to be done for these drugs to safely and effectively treat more people. But the result could fundamentally change the options for those struggling with addiction. Effective medications exist for opioid and alcohol use disorders, but a lot of patients struggle to follow through with treatment. Those suffering from opioid use disorder often must go in person every day to take methadone. Other addictions, like cannabis use disorder and cocaine use disorder, don’t yet have FDA-approved treatment.

It often takes years for new indications to be approved, with more time needed for certain groups. Li, whose research lies largely in pharmacogenetics — the study of how genes influence medication response — said it’s important that new research shows how different people experience GLP-1s. She also said there are more questions to ask about the long-term use of these drugs. The weight and metabolic effects of GLP-1s seem to wane after people stop the medication, but doctors don’t yet have much long-term data on these effects.

“To make sure that this is safe and accessible for patients, it really requires adequate funding to support these research endeavors,” Shen said.

Despite the hurdles to approval, researchers remain positive — and largely, so do patients. Vaduganathan said that patients often initiate conversations about GLP-1 prescriptions, which they’ve rarely done for any other class of drugs, including other highly effective ones.

“That has actually improved shared decision-making,” he said, “because often we now have two invested parties that are united with shared goals.”