Diabetes drug could be a game-changer for obesity, new study finds
A drug recently approved to treat type 2 diabetes is also extremely effective in reducing obesity, according to a new study.
The drug, called tirzepatide, acts on two natural hormones that help control blood sugar and are involved in sending signals of fullness from the gut to the brain..
Researchers noticed that people who took the drug for their diabetes also lost weight. The new trial focused on obese people without diabetes and found even greater weight loss.
Those who took the highest of the three doses studied lost up to 21 percent of their body weight — up to 50 to 60 pounds in some cases.
Nothing has provided that kind of weight loss except surgery, said Dr. Robert Gabbay, scientific and medical director of the American Diabetes Association. The full study was presented Saturday at the ADA’s annual convention in New Orleans and simultaneously published in the New England Journal of Medicine.
Another obesity treatment approved last year called semaglutide, from Novo Nordisk, results in average weight loss of up to about 15%. Previous generations of weight-loss drugs only reduced about 5% of weight and many had prohibitive side effects.
“We haven’t had tools like this,” Gabbay said. “I think it’s really exciting.”
For most trial participants, the side effects of tirzepatide were not serious, said Jeff Emmick, vice president of product development for the diabetes division of pharmaceutical giant Lilly, which makes the drug.
About 15% of participants who received the active drug dropped out of the 72-week trial, about a third due to gastrointestinal side effects. Meanwhile, 26% of trial volunteers who received a placebo dropped out. Emmick said he thinks they may have been frustrated with their lack of weight loss.
On May 13, the Food and Drug Administration approved tirzepatide, under the trade name Mounjaro, for the treatment of type 2 diabetes.
Tirzepatide is not yet available for weight loss, but Lilly hopes to have an updated schedule from the FDA later this year, Emmick said. Before approving the weight-loss drug, the regulatory agency may first want Lilly to complete other ongoing studies looking at tirzepatide in people with obesity and diabetes and adding lifestyle changes on the drug regimen.
Weight loss of 15% to more than 20% also has the potential to change the way doctors treat diabetes, Gabbay said, focusing on lowering blood sugar to aim for complete remission.
A previous study of tirzepatide in diabetes showed that half of participants who were early in their diabetes went into remission while taking the drug.
“It’s a potential shift in how we think about therapy for people with type 2 diabetes,” he said.
What’s not yet known, Gabbay said, is whether remission achieved this way will reduce complications typical of diabetes, which can include cardiovascular disease, nerve and kidney damage, and limb amputations.
It’s also not yet clear whether tirzepatide will provide the cardiovascular benefits of semaglutide, said Dr. David Rind, primary care physician and chief medical officer of the Institute for Clinical and Economic Review in Boston.
It would be useful, Rind said, to conduct a comparative trial between the two drugs to see if there are any differences in their health benefits.
“The question is, is tirzepatide better than all of these (other weight loss) drugs?” Rind said. “There are certainly reasons to think it might be, but I don’t think it has been proven yet.”
Positive side effect
It certainly made a difference for Mary Bruehl, 63, of Norman, Oklahoma.
She joined the diabetes trial for tirzepatide in August 2019 because she had heard weight loss might be a side effect of the drug. After years of “doing everything right,” Bruehl’s diabetes and weight control had slipped.
A hip replacement had her nearly immobilized, leading to weight gain and lack of energy. “It just seemed like there was nothing I could do to remove it,” said Bruehl, an attorney. “My stomach hasn’t seen the end of all the food in the world.”
Diagnosed with fatty liver disease in June 2019, a concerned Bruehl began skipping breakfast — with the exception of coffee — to cut calories and lose some weight.
Starting tirzepatide in September, she started losing 5-10 pounds a month. As of July 1, 2020, she had lost nearly 60 pounds, giving her one of the best results seen with the drug so far.
The more Bruehl lost, the better she felt and the more she could resume weekend hiking and other physical activities, she said, which helped her feel even better.
The drug kept her from overeating, Bruehl said. If she overdid it, the food would come back. “I learned to stop before I got that feeling,” she said.
Bruehl no longer needed metformin for his diabetes, and his fatty liver disappeared. The only negative side effect was nausea, which Bruehl experienced the day after each of his weekly tirzepatide injections. An anti-nausea pill that morning took care of it, she says.
The biggest challenge for Bruehl was adjusting to how people treated her differently after the weight loss. “I went to body image counseling and to work through some of the issues I was having,” she said, adding that she needed time to come to terms with what she was seeing in the mirror and to stop reacting angrily to comments about his new number. “It took me a while to feel comfortable in my own skin again.”
Bruehl started dating after being single for many years and now has a long-term partner.
“I feel more balanced. I feel like I’m more myself now,” she said. “This trial gave me my life back.”
Specifics of the test
The new tirzepatide trial, called SURMOUNT-1, included more than 2,500 volunteers who met the medical definition of obesity, having a body mass index of 30 or more, or had a slightly lower BMI but at least a weight-related health problem.
The average BMI of the participants was 38, 70% were white and almost as many were women. Almost everyone on the drug saw improvement in blood sugar, blood pressure, and lipid levels. The trial began in December 2019 and ended despite the ongoing COVID-19 pandemic.
Dr. Ania Jastreboff, an obesity medicine specialist at Yale Medicine who helped lead the trial, said her patients responded in a variety of ways to tirzepatide, as they would to any other drug, some don’t. getting no benefit. But nine out of 10 lost weight, and at the highest dose, 15mg, they lost an average of 52 pounds each.
Drugs like semaglutide and now tirzepatide “allow us to really take care of our patients the way we need to take care of them,” Jastreboff said. “They effectively regulate biology and help people restore body weight.”
Jastreboff said she was able to help most of her patients overcome the side effects of newer weight-loss drugs, either by cutting down on certain foods or by eating less in general. “If you eat beyond the point of satiety” with these drugs, she said, “you’ll feel like you’ve eaten three Thanksgiving dinners.”
Jastreboff said she often had to help patients overcome the blame they felt for carrying extra pounds. She sees obesity not as an individual’s fault, but as a struggle against biology’s will to keep the extra pounds off. “These drugs target that physiology in a safe and effective way,” she said.
Patients will need to continue taking drugs for weight loss, just like with drugs for other chronic conditions, such as diabetes, high cholesterol and high blood pressure, she said. It’s possible that once they maintain a lower weight for a while, they could continue on a lower dose or even reduce completely, but this needs to be investigated, she said.
A barrier for many people will be the price of weight loss drugs.
It’s too early to know what price Lilly will set for tirzepatide. Mounjaro, the same drug used to treat diabetes at the same doses, sells for just under $1,000 a month.
Semaglutide was released last year for weight loss and has been in short supply ever since, Rind said. It costs about $1,600 per month for the 2.4 mg weight loss dose, which is higher than the 1 or 2 mg doses used to treat diabetes. Like other weight-loss drugs, semaglutide is not covered by many insurance plans.
“Access and cost – that’s something we work on every day as providers,” Jastreboff said.
Bruehl recently began taking a low dose of semaglutide to treat his diabetes and his weight which has started to recede. The insurance covers all but about $30 per month.
She agrees that she’ll probably have to take it forever to keep the weight off, just as her inherited risk of diabetes means she’ll probably have to deal with it forever too. Exercise and a careful diet will also need to be part of her ongoing regimen, she said.
“It’s going to take a lifetime of dedication.”
Contact Karen Weintraub at [email protected]
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