Diabetes drugs have found new life as weight-loss drugs

To understand David Scomo's struggle for a healthy body weight, you have to go back a few decades.

"Weight control has always been an issue for me, something I've been doing probably since I was a kid," he says.

Skomo, 50, chief operating officer of WellDyne, a pharmacy benefits management company, was a bit overweight in middle and high school, but never obese. As he got older, however, he found it harder and harder to reach a healthy weight.

It wasn't because he wasn't trying. He was watching his diet. He exercised. And Skomo made some progress, but, as is often the case with weight loss, the pounds came back.

"If you work really hard, diet and exercise, you will lose weight," he says. "But it also means having the willpower to not eat when your body tells you it's the way out. That's where it really gets tough."

But Skomo never tried weight-loss drugs. "Some of the early products didn't do much good," he says. "They were dangerous, addictive, and I didn't want to mess with it."

However, Scomo read the positive results of the drug Wegovy (semaglutide), which the FDA approved in June 2021, and decided to try it. At the time, Skomo was suitable to take the drug because he had a body mass index (BMI) of 29 and hypertension. A pharmacist by training, Skomo said the fact that Vegovi had a different mechanism of action was a compelling reason to try it. "I saw that this drug was significantly different from previous generations of weight-loss drugs," he says. Skomo discussed it with his wife, who is also a pharmacist, and she agreed. His only reservation was the possibility of gastrointestinal side effects.

Nearly a year later, he has lost 18 percent of his weight and has a BMI of 23. "I said to myself, 'If I could lose about 30 pounds over time, I'd be thrilled,'" he says. "And now I've lost about 35 pounds of weight."

Saxenda was the first

Stories like Scomo's are one reason for the emergence of a new class of weight-loss drugs. The idea that pharmaceutical drugs can stop the obesity epidemic in the United States is very appealing, but weight-loss drugs have a mixed history of lack of long-term efficacy and, in some cases, lack of safety.

But now there is a cohort of new drugs with new mechanisms of action that could bring medication-assisted weight loss back into the medical mainstream, although their high price could be a problem. Novo Nordisk's Saxenda (liraglutide), first approved in 2014, was at the forefront. Results of a clinical trial published in 2015 showed that nearly two-thirds of adult patients lost at least 5% of their body weight after 56 weeks of taking Saxenda. One-third of patients lost more than 10%.

The next was Wegovy, which is also produced by Novo Nordisk.

Then, in late April of this year, Eli Lilly caused a furor when it announced the results of phase III trials of its weight-loss drug Mounjaro (tirzepatide). The company said the drug helped people lose 22.5 percent of their body weight.

All three drugs were first approved by the FDA as diabetes drugs, and then Novo Nordisk and Eli Lilly began seeking agency approval to add an indication for their use in weight control. The FDA approved Munjaro as a type 2 diabetes drug in May. Eli Lilly is expected to seek to add the drug to the weight control indication list if current clinical trials prove successful.

A paradigm shift

Robert Kushner, M.D., one of the researchers involved in Wegovy's phase 3 trial and a professor at Northwestern University's Feinberg School of Medicine, tells Managed Healthcare Executive that the drug represents the beginning of a second generation of pharmacotherapy for obesity. "There has been a paradigm shift in the treatment of obesity that parallels our understanding of the underlying appetite dysregulation underlying this disease," he says.

Saxenda was a first step in a new direction, but requires daily
Kushner notes that Saxenda was a first step in a new direction, but requires daily administration. It was a big step forward when Wegovy, and now Mounjaro, proved effective but required weekly rather than daily injections, Kushner notes.

According to Kushner, these new therapies have the potential to correct the appetite dysregulation underlying weight problems in many patients. "By using the appetite effects of natural gastrointestinal and pancreatic hormones, we can biologically alter appetite dysregulation," he says.

All three drugs act on glucagon-like peptide-1 (GLP-1), a natural hormone released in response to food intake that regulates appetite and caloric intake. By binding to the GLP-1 receptor and activating it, the drugs help patients get fuller faster. In addition to affecting GLP-1, Munjaro also affects glucose-dependent insulinotropic polypeptide (GIP), a hormone that regulates blood glucose levels. Clinical trial data show that this dual approach can enhance the weight-loss effect. However, all three drugs can lead to gastrointestinal side effects.

Kushner says that in the case of Wegovy, it is important that the prescriber and
patient should be in regular contact to clarify dosage and dietary intake. However, Kushner emphasized that repurposed diabetes medications cross the efficacy threshold: "A weight loss of more than 15% is significant because it more closely matches patients' expectations of a good weight loss response and is associated with clinical improvement in blood pressure, blood glucose levels and well-being."

High prices

Evidence of efficacy and long-term benefits will be important for these weight-loss drugs because the manufacturers have set a high price for them. Payers will scrutinize them in terms of cost-effectiveness, which in the case of weight loss drugs is a difficult task. How are the savings associated with preventing the many diseases that result from being overweight and obese taken into account?

In 2019, a team of researchers presented the results of a cost-effectiveness analysis of six weight-loss drugs, including semaglutide (it has not yet been named Wegovy) and Saxenda, along with a lifestyle intervention plan. The results, published in the journal Obesity Science and Practice, showed that semaglutide was inferior to Lomaira (phentermine) in effectiveness after one year. However, weight loss with Lomaira slowed after one year, while semaglutide maintained its weight loss effect for five years. However, the researchers, some of whom reported receiving consulting fees from Novo Nordisk, concluded that semaglutide was not cost-effective because of its high price.

But there are some caveats. The analysis was based on time horizons of one, three, and five years, so it could not account for long-term savings from healthy body weight. In addition, the analysis was conducted before Novo Nordisk began selling semaglutide as Wegovy.

The researchers used an annual cost of $8,273, based on the price of semaglutide as a type 2 diabetes drug (as a diabetes drug, semaglutide is sold under the trade name Ozempic). Wegovy's price is higher: the monthly price is $1,349, according to Novo Nordisk's Web site, which equates to an annual price of $16,188.

Skomo said he hopes approval of additional drugs will be better for patients, not only in terms of finding the right drug, but also in terms of making it easier to get drugs to market.

"We're going to see some competition in the marketplace for formulary inclusion and things like that, which will help start to bring down the cost of drugs," he says. "So I think it's a win-win when we get more products on the market."

Scomo says WellDyne recommends its clients add Wegovy coverage, although he says most have not yet taken that advice. Kushner says cost is always an issue with drugs, but he's frustrated by insurers who either limit or completely exclude drugs from that category.

"The dilemma is that we have effective and safe drugs for our patients to help them get healthier, but they can't afford them," he says. "Of course, we need to expand coverage, and the cost needs to come down."

More news