The upsides and downsides of blockbuster weight loss drugs

With another blockbuster weight loss medication poised to come on the market this year, the director of the Medical University of South Carolina’s Weight Management Center sat down with MUSC Catalyst News to talk about:

• The remarkable percentage of pounds dropped by people using the new weight loss drug tirzepatide in clinical trials.
• Other drugs already on the market, Wegovy and Saxenda, that have made a splash.
• How their popularity is causing medication supply shortages for people with Type 2 diabetes.
• Who qualifies for the prescription weight loss medications.
• Their side effects and costs.

That’s a lot of ground to cover, but Patrick O’Neil, Ph.D., is more than up to the task. In addition to leading the Weight Management Center in the MUSC Health and Wellness Institute in Mount Pleasant, he’s a professor in the College of Medicine at MUSC and a former president of The Obesity Society. O’Neil also studies and leads clinical trials on medications and treatments designed to help people manage their weight – including one drug discussed in this article.

The new weight loss drug, tirzepatide

There’s a lot of buzz about a weight loss medication expected to go on the market this year. Its manufacturer, Eli Lilly, hasn’t announced the brand name yet, but the medication it contains is called tirzepatide.

 

Tirzepatide is already in a diabetes drug called Mounjaro. The weight loss drug might contain more tirzepatide than Mounjaro does, to boost its power in helping people shed pounds. 

That power is remarkable. O’Neil said tirzepatide worked so well in clinical trials for weight loss that it earned fast-track designation from the Food and Drug Administration. That speeds up the process of getting important new medications to the people who need them.

“In a phase 3 trial, they achieved weight losses as high as 20% of the person’s starting body weight,” O’Neil said. That was 50 to 60 pounds in some cases.

Tirzepatide works by helping the patient feel full on less food and slowing the passage of food through the digestive tract. There’s no question the weight loss it leads to is beneficial for people who are overweight or obese. But there are some other factors to consider, which O’Neil addresses later in this article.

Other weight loss drugs already on the market

Tirzepatide comes on the heels of two other injectable weight loss drugs that have made a splash in recent years. Like tirzepatide, they evolved from diabetes medications, reducing appetite and slowing the emptying of food from the stomach.

The first was liraglutide, brand name Saxenda, for obesity.It was originally only marketed for diabetes treatment under the brand name Victoza.

“What they found in clinical trials was that people with diabetes who were taking liraglutide also tended to lose weight. So they started studying it in a different dose, a higher dose for weight loss specifically, with or without diabetes. And they found that it had a significant effect on weight loss. It was an average loss of about 6 or 7% or more over a year,” O’Neil said.

The next big weight loss drug to emerge was semaglutide, under the brand name Wegovy. As a diabetes treatment, it’s called Ozempic. Again, the weight loss version includes more semaglutide than the diabetes treatment.

“It’s basically mimicking a naturally produced peptide that's made in the gut. It tends to help regulate glucose and contribute to a feeling of fullness. This is also true of liraglutide and tirzepatide,” O’Neil said.

He played a role in ensuring Wegovy worked as it was supposed to. “MUSC participated in many of the trials for semaglutide. You see an average weight loss of about 15% to 16% of the person’s starting weight. That's a much higher percentage than had ever been seen with any weight loss drugs previously approved by the FDA.”

O’Neil said some scientists have called semaglutide a game changer. “It is a big deal. But it's not a cure-all. I want to stress that. You need to use FDA-approved obesity medications along with diet and exercise. So they're not intended to be a simple solution to a complex problem. But this is a substantially greater effect than we've seen from any previously approved obesity medication.”

Effects on diabetes drug supply

That game-changing reputation came with a cost – for both people with diabetes and people who wanted to lose weight. High demand for Wegovy and off-label prescribing of Ozempic for weight loss led to shortages that have some patients scrambling for alternatives.

Mounjaro is on the FDA’s drug shortages list, too. So is another diabetes drug called Trulicity, which is not a weight loss drug but is being prescribed off-label as well, because in some cases, diabetics who used it lost weight.

Who qualifies for the prescription weight loss medications?

When it comes to the weight loss medications described earlier that are already on the market, there are qualifications. Saxenda is meant for adults with a body mass index of 27 or higher and kids 12 to 17 who are obese. Everyone who takes it is asked to cut calories and increase exercise.

Wegovy is for adults with a body mass index of 27 or higher as well. They’re supposed to eat less and move more, too. The FDA recently approved Wegovy for kids 12 and up who have a high body mass index.

Side effects and costs

O’Neil said just about every drug has side effects, and weight loss medications are no exception. “These drugs that I've been talking about are all gut drugs, basically. They're mimicking hormones that are produced in the gastrointestinal system. And so their side effects tend primarily to be GI side effects. Many complain of some nausea, less frequently, vomiting, diarrhea or constipation.”

He said patients should start with a low dose, gradually increasing the dose to the target level. 

“What we found in the studies is that we do see the side effects, such as diarrhea and nausea and so on, tend to be generally transient. So over time, people tend to get over them. We have had very few people have to come off the drugs in studies because of side effects.”

He said gallstones and gallbladder problems are also potential problems. But the discomfort may not be just physical. The medications are expensive, O’Neil said – more than $1,000 a month. “Most insurance plans do not cover medication or any kind of treatment for obesity. So it is a medical condition that's really discriminated against in a lot of different ways.”

It’s also a condition that’s being carefully studied as the number of people who are overweight or obese grows.“I always stress that no drug, no obesity medication works for everybody. No obesity medication's going to work by itself without you doing your part. And they only work when you take them. Butpeople need to treat these medications as serious treatments for a serious condition.”