These Drugs Are Changing the Fight against Obesity | BU Today

Millions of Americans have found an unexpected benefit from their diabetes drugs—weight loss—opening a whole new avenue for treatment of obesity and a whole new market for pharmaceutical companies.

Diabetes medications Mounjaro and Ozempic have proven effective for chronic weight management. Now rebranded as Wegovy and Zepbound, respectively—the drugs have won FDA approval as obesity treatments. Their popularity is surging: even Oprah has reportedly climbed on the bandwagon.

“It’s become increasingly apparent that these medications can really cause significant weight loss in addition to lowering blood glucose,” says Ivania Rizo, a BU Chobanian & Avedisian School of Medicine assistant professor of medicine in endocrinology, diabetes, nutrition, and weight management and director of obesity medicine at Boston Medical Center.

She says these drugs—and others like them now in the development pipeline—can make a clear and significant impact on health in a country where more than 40 percent of the population is considered to have obesity and many more are overweight. 

Traditional treatments for type 2 diabetes take care of patients’ blood glucose problems, but at the same time often cause them to gain weight. The new drugs lower glucose levels, but also lower weight, “which is amazing,” Rizo says, and “a huge game changer” for diabetes.

Mounjaro and Ozempic were developed to help people with type 2 diabetes control their blood sugar. The key ingredient in Ozempic is semaglutide, which was first approved for diabetes treatment in 2017. In Mounjaro, it’s tirzepatide. That drug went on the market in 2022. 

Both drugs proved effective in helping people lower their blood sugar levels, with significant weight loss as a side effect. Many people then sought the drugs for off-label use to combat weight, leading to reported shortages. The government approved Wegovy, containing semaglutide, for obesity in 2021 and Zepbound, containing tirzepatide, in November 2023.

Insulin is a hormone in the body that helps control blood glucose levels by moving glucose into cells where it is used immediately for energy or stored for the future, as described by the American Diabetes Association. Injecting additional insulin has long been the traditional treatment for elevated glucose levels for both type 1 and type 2 diabetes.

The new class of drugs works differently. Semaglutide mimics the action of GLP-1, a hormone that helps to regulate blood glucose levels using insulin and glucagon, a hormone that keeps your glucose levels from dropping too low. Tirzepatin mimics GLP-1 and a second hormone, GIP, which work together to stimulate insulin secretion

“They were initially studied for that glucose-lowering effect,” Rizo says. “We do know now that, depending on the molecule, they also cross the blood/brain barrier and go to areas like the hypothalamus and receptors in the brain that can decrease appetite and increase satiety. In patients with diabetes it does lower blood glucose, and at the same time decreases weight. In patients without diabetes we tend to see a greater weight loss.”

Still, these are prescription-only medications intended to treat obesity, which is defined by the Centers for Disease Control and Prevention as a body mass index (BMI) of 30 or above and for those with a BMI of 27 and above with obesity-related comorbidity. Rizo prefers the World Health Organization definition, which instead of setting a numerical level describes obesity as abnormal or excessive fat accumulation that presents a risk to health.

“Obesity is a major public health concern in the United States and has been linked to many health problems such as heart disease, stroke, diabetes, high blood pressure, sleep disorders, and breathing problems,” the Food & Drug Administration says.

Rizo is careful not to describe the new drugs as “diet drugs.”

We talk about obesity medications, because obesity is a chronic disease that’s progressive,” she says, “and one of the major benefits in these medications like Zepbound is not only are we seeing weight loss, we’re also seeing significant metabolic effects; people’s physical function is increased significantly with these medications.”

Key changes include decreases in systolic and diastolic blood pressure, she says. “We start patients on these medications, and then many times you are able to significantly decrease their blood pressure medications; they may not need them anymore.” One major study, published in December 2023, demonstrated a 20 percent reduction in major adverse cardiovascular events at a particular dose of Semaglutide in people with obesity or who are overweight (without diabetes) and have cardiovascular disease. Additional studies of the drug’s effects on fatty liver disease, heart failure, and sleep apnea are underway.

Of course, access to these drugs is another issue. Demand for their weight loss effect has created shortages, some insurances will pay for them for diabetes but not for weight loss, and the price in America can be substantially higher than in Europe and elsewhere. 

“I think a lot of us feel that Novo Nordisk, who’s making a significant amount of money on semaglutide, could continue to increase efforts in terms of supply,” Rizo says. “And there have been multiple supply chain issues, like with the actual pen that we use for injecting.” But she says other drugs in the pipeline may be available in pill form, potentially reducing some of those problems.

Of course, the new drugs are also attracting customers who see them as an easy answer for cosmetic weight loss, the “I just want to take off 10 pounds” group. Even if supply, price, and access weren’t issues, Rizo wants those individuals to think twice about using these drugs.

“There are risks and benefits to be weighed, and if you want to maintain the weight loss the medication does need to be used chronically,” she says. “There are side effects that may not be worth the benefits. If you want just to lose 10 pounds, it may not be worth the side effects. The most common are nausea, constipation, and diarrhea. Approximately 30 percent of patients can get those gastrointestinal side effects, [especially] during the escalation phase of the medications.”

Ultimately, the new drugs mean more choices for people with obesity, working with their medical providers to find the best treatment. “Obesity is not one disease, the same way cancer is not one cancer, right?” Rizo says. “What we want to be talking about is more options that potentially may help more people. And making sure that the patients who really need this medication get it, which right now I think is not always the case.”