GLP-1 drugs are famously super effective — how that’s now messing up new drug trials

The GLP-1 PR has been a little too good.

Everyone knows the drugs lead to rapid weight loss — including participants in supposedly “blind” drug trials. So now, when those participants don’t drop pounds, they drop out.

Pharmaceutical manufacturers are reporting widespread instances of patients quitting their clinical trials prematurely once they realize they’ve been assigned a placebo instead of the real thing, raising questions about how trials for obesity drugs should be run moving forward.

Raymond Stevens, CEO of Structure Therapeutics Inc., confirmed to Bloomberg that “people learn pretty quickly whether they’re on placebo or not.” It’s made conducting clinical trials for Structure’s experimental weight loss pill “a challenge.”

Many people who opt into these clinical trials are looking for solutions to their health problems. When they don’t get the results they want — or, in the case of GLP-1s, the results they’ve come to expect — they feel they’ve wasted precious time that could have been spent getting healthier.

Bloomberg spoke with a 57-year-old New England–based clinical trial participant who gave his name as Tom. He said he stayed on a study for Eli Lilly & Co.’s new retatrutide shot because he didn’t think he could get Wegovy or Zepbound through his insurance.

Tom, who survived a heart attack over a decade earlier, lost 45 pounds in less than a year at the start of the trial. But when he didn’t experience any side effects like nausea or vomiting, he had a gut feeling that the changes weren’t due to the drug.

“I could tell the only reason I was dropping [the weight] was because I was being really vigilant about the diet,” he said. “My appetite was still 100% the same. Over time, my weight drifted back up again, and it became pretty clear I was on the placebo.”

If he can get his insurance to cover Wegovy — which he might be able to do, under the premise that it helps protect against heart disease — he said he would leave the retatrutide study.

Social media hasn’t helped pharma companies retain trial patients, either.

Some participants have been posting about their trial experiences with Eli Lilly’s new pill, orforglipron. 

“People aren’t supposed to be talking about these things, but it was on Reddit — during the trial,” Stevens told Bloomberg.

And Eli Lilly is feeling the heat: A spokesperson told Bloomberg that in a major orforglipron trial, 6.2% of placebo patients quit because they were unhappy with their weight loss, and 2.5% sought other ways to drop pounds, which sometimes meant they took different obesity medications.

That’s not allowed, the spokesperson said, but participants could stay in the trial as long as they quit the study drug.

With hundreds of weight-loss drugs in the experimental phase at any given time — and with trillions of dollars at stake — these companies share a growing appetite for a restructured clinical trial process that would better account for these flukes, especially because skewed results could make their drugs look less effective.

Swiss drugmaker Roche Holding AG, for example, already made some changes. The plan is to offer patients a “long-term extension period” for their trials, giving whoever receives the placebo a chance to then switch and take the experimental drug. 

Manu Chakravarthy — Roche’s head of cardiovascular, renal and metabolism product development — has said that the company believes this will help recruit and retain patients.

“We’re doing everything we can to keep people engaged and into the trials,” he said.

The president of Eli Lilly’s cardiometabolic health unit, Kenneth Custer, has said that Eli Lilly is open to making similar changes. 

Novo Nordisk, the producer of Wegovy, said it “offers counseling and follow-up as part of its trials, helping some patients on placebo make lifestyle changes and lose weight as well,” according to Bloomberg.

For aggressive diseases like cancer, trials typically avoid placebos, instead assigning one group an existing medicine while giving the other group the experimental drug.

Some patient advocates, including World Obesity Federation board member Amber Huett-Garcia, think the current obesity drug clinical trial set-up has failed its participants.

“It almost feels like the definition of obesity and how we understand it as a disease has not made it into clinical-trial standards of care,” Huett-Garcia told Bloomberg.

In an interview last year, Custer admitted how easily GLP-1s can be “sort of de-blinded.” 

He implied that asking patients to sign up for a 72-week experience where they might be randomized to a placebo could, in some cases, be gambling with their health. 

“It’s a long time to go without efficacy,” he said.