• Posted October 10, 2023

Wegovy, Ozempic Help Folks Lose Weight, But How?

As many doctors and patients hail the advent of weight-loss drugs like Ozempic and Wegovy as the perfect fix for obesity, some experts are urging caution.

The drugs are not well-tolerated by everyone struggling with obesity. For some folks, the weight piles back on as soon as the medication stops. There are also financial and ethical considerations, according to a commentary published online recently in the Journal of Clinical Investigation.

More research is needed to better understand the medications, said endocrinologist Dr. Michael Schwartz from the University of Washington School of Medicine, in Seattle.

Many experts seem to be saying “OK, we've fixed this problem. We're done,” said Schwartz, co-director of the school's Diabetes Institute and a co-author of the commentary.

“We shouldn't be complacent, and assume that these drugs are the answer to these chronic conditions,” Schwartz said in a university news release. “We are giving drugs where we don't understand totally how they work."

Wegovy (semaglutide) is approved by the U.S. Food and Drug Administration for treatment of obesity, a problem affecting about 42% of the U.S. population. Ozempic (semaglutide) and Mounjaro (tirzepatide) are approved for type 2 diabetes, but are also prescribed for weight loss.

The medications mimic the action of naturally produced hormones, including glucagon-like peptide-1 (GLP-1). Patients feel full when eating less because of the increase in insulin, appetite suppression and reduced gastric emptying.

Mounjaro also mimics a closely related hormone called GIP, which targets receptors for both GIP and GLP-1. It has a more powerful effect.

It appears the drugs target brain systems that protect against weight loss, Schwartz said.

The body's energy homeostasis system mounts adaptive responses when weight loss greater than 5% occurs, and these drugs appear to inhibit this response.

But that adaptive response returns when someone stops taking the medication, Schwartz said.

“Once the drug is discontinued, the lost weight is regained at an extraordinary pace, even faster than when it was lost -- presumably because the energy homeostasis system, having been suppressed for months, suddenly awakens,” the authors suggested.

The authors also pointed to ethical and financial questions, such as whether a teenager should start taking one of these powerful drugs. They then might need to take them for a lifetime at the cost of $1,000 a month or more.

There are also side effects to consider, among them nausea, pain, depression and gastrointestinal (GI) problems.

Schwartz noted that a better understanding of how signals coming from the GI tract communicate with the energy homeostasis system might enable scientists to help people control body weight in a more specific manner.

Drugs could potentially be developed with much greater specificity than is achieved with the current drugs, he said.

This could mean having fewer side effects. The potential for unanticipated off-target side effects with these drugs may grow as more people take them, Schwartz added.

More information

The U.S. Centers for Disease Control and Prevention has more on obesity.

SOURCE: University of Washington School of Medicine, commentary, Oct. 5, 2023