Experimental Weight-Loss Drug Shows Surgery-Like Results in New Trial

Experimental Weight-Loss Drug Shows Surgery-Like Results in New Trial

Photo: Darron Cummings (AP)

Pharmaceutical company Eli Lilly last week disclosed the latest data from a phase III trial of its experimental type 2 diabetes and obesity drug, tirzepatide: People who took the drug lost up to 22% of their body weight and achieved far greater weight loss on average than the placebo group. The findings, while preliminary, suggest tirzepatide may become the second major medicine in a new era of obesity treatments, provided that patients can actually afford it.

The SURMOUNT-1 study involved over 2,500 patients who were overweight (defined as having a body mass index from 25 to 30) or obese (a BMI over 30), and also had a condition possibly related to their weight, with the exception of diabetes. These patients were randomized to receive either a placebo or one of three different doses of tirzepatide, delivered weekly via an injection under the skin. In addition to the treatment, each group was advised to go on a reduced calorie diet and increase their physical activity. The trial was ran in the U.S., Argentina, Brazil, China, India, Japan, Mexico, Russia, and Taiwan.

Each group lost weight on average over the course of 72 weeks, but the loss was much greater in the tirzepatide groups. Those given a 5-milligram dose lost 15% body weight on average; those on a 10-milligram dose lost 19.5%, and those on the 15-milligram dose lost 20.9%, compared to the 3.1% weight loss seen in the placebo group. When accounting for people who dropped out of the study early, the study’s researchers estimated that people on the highest dose lost an average of 22% body weight, or around 50 pounds. Adverse effects were generally mild to moderate, but included nausea, vomiting, and diarrhea, which often occurred early on as people’s doses escalated.

The findings have yet to be published in a peer-reviewed journal, so they should be taken with some caution. But the figures seen here, assuming they’re sound, are simply unprecedented for a drug, according to Samantha Harris, an endocrinologist at the Scripps Clinic who focuses on weight management and diabetes care.

“The ability to lose 15%, 20%, or 25% of total body weight with medications is incredible, as these types of results have typically only been seen in patients who have undergone bariatric surgery,” Harris said in an email to Gizmodo.

Last June, Novo Nordisk’s Wegovy won approval from the Food and Drug Administration for treating obesity. Wegovy is a higher-dose version of semaglutide, the same active ingredient used in its type 2 diabetes medications Ozempic and Rybelsus. The pivotal trials for Wegovy showed that patients lost an average 15% body weight on it—numbers now matched or surpassed by tirzepatide.

Both semaglutide and tirzepatide work by essentially boosting levels of a hormone called GLP-1. But tirzepatide also boosts levels of a second hormone called GIP (glucose-dependent insulin tropic polypeptide). These incretins, as they’re known, play a crucial role in regulating our metabolism and hunger. And the combination of GLP-1 and GIP activity seen with tirzepatide could very well account for its superiority over semaglutide in trials so far, Harris said.

Incretin-based drugs have shown to be valuable and safe treatments for type 2 diabetes for over a decade now, particularly through increased insulin production that helps keep blood sugar in check. But the continued success we’re seeing with these drugs outside of diabetes might just be the start, according to Michael Albert, an obesity specialist. Patients taking them have also shown improvements in cardiovascular health, for instance, and some studies have even suggested they could provide a protective effect against dementia, though more research will be needed there to confirm any benefits.

“I think we’re seeing a new age of therapeutics here. And these drugs are really going to make a significant difference in our fight against many of these chronic diseases that we’ve really struggled to get on top of,” Albert told Gizmodo by phone.

As promising as these drugs are, some critics have questioned the inherent value of obesity treatments, especially given their overall spotty track record. Another pressing issue, even for those who want to take these treatments, has been affordability. The out-of-pocket price of Wegovy is around $1,400 a month, and neither it nor other obesity treatments are eligible to be covered by basic Medicare plans. Many private insurers have declined to cover Wegovy as well. And since last year, Novo Nordisk has been dealing with manufacturing shortages, which have made it even harder for new patients to obtain the medication.

“The drugs themselves appear to be great, but Wegovy is expensive, and the others probably will be too,” Stephan Guyenet, a neuroscience researcher, author, and review editor at Frontiers in Nutrition, told Gizmodo in an email. “This is especially true in the U.S., where Wegovy costs about four times more than in other countries. So the main question becomes one of access.”

Novo Nordisk has said that its factory issues will clear up by the second half of the year. Based on earlier trial results, Eli Lilly had already submitted tirzepatide for FDA approval as a diabetes treatment late last year, and a decision on that indication is expected before the end of the second quarter. Eli Lilly will almost certainly submit the drug for approval as an obesity treatment as well, though no clear timetable appears to have been set just yet.

Assuming that tirzepatide’s results stand up to muster, we will likely have two of these newer-generation drugs available next year, and other, even more effective therapies could follow over the next decade. That competition might drive prices down, or it could at least bolster the case for their widespread coverage.

“My one outstanding concern is: What does access to these medications look like? Are they going to be covered long term?” Albert said. “If we can nail the coverage part, which I think will come with greater momentum around the data reporting, the sky’s the limit. And I think for patients who will benefit from these treatments, there’s a real hope on the horizon.”

One way or another, it’s likely that these drugs will change the conversation to one that is focused less on personal choices and more on the metabolic underpinnings of obesity.

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