At the end of an apparently ubiquitous commercial for the telehealth company Ro, a characteristically surprised Charles Barkley speaks for us all when he comments, “Wait, you’re telling me they have GLP-1. the pill Now to lose weight?”
They do – and it was just as wildly popular as its injectable predecessors. Just about 10 weeks after it was approved by the US Food and Drug Administration, Vigovi pills are now estimated to be part of the daily diet of about 400,000 Americans. And the field of weight loss therapy is about to turn even more heads.
A second pill is under FDA review, expected to hit the market next month, and several others are in clinical trials. Some companies offer drug testing that only needs to be taken once a month. And an even more powerful next generation of drugs is fast approaching, with trial results — including some new ones Thursday — leaving current options in the dust in terms of effectiveness.
“We are entering the second phase of this type of use of the GLP-1 system,” said Dr. Judy Doshi, an endocrinologist at Beth Israel Deaconess Medical Center and an assistant professor at Harvard Medical School.
The next wave may be driven by cost and convenience as much as by new treatment approaches. Weight-loss pills — those already on the market and awaiting approval — have received new price cuts for US patients in a deal that pits both drugmakers against the Trump administration, even as insurance coverage may remain intact. For many.
And more powerful drugs on the horizon could bring options for people who don’t get enough benefit from currently available treatments — but doctors warn of the risk of inappropriate use.
One such drug is retatrutide, a weekly injectable drug in development at Eli Lilly, which also makes Monjaro for diabetes and Zipbound for weight loss.
These drugs are based on the active ingredient terzapatide, which mimics two hormones: GLP-1 and GIP. Retatrutide raises the ante by adding a third component called glucagon, earning it the name “triple G.”
This breaks the record for weight loss by medication; In clinical trial results reported in December, retatrotide reduced participants’ body weight by an average of 29%, or about 71 pounds, after 68 weeks in a study of people with knee osteoarthritis. The drug was also associated with reduced knee pain.
In new results released Thursday about type 2 diabetes, in which patients lose less weight with the drug, Lilly said the drug reduced A1C blood sugar levels by an average of 1.7% to 2% over 40 weeks and led to an average weight loss of 17%, or about 37 pounds. That’s more than the results for Monjaro, which in a separate trial showed a 1.7% reduction in average A1C and about a 9% weight loss at the highest dose.
“It looks like maybe we’re getting to the next level with drugs like retatroid,” said Dr. Judith Koerner, an endocrinologist and director of the Metabolic and Weight Control Center at Columbia University’s Vigilance College of Physicians and Surgeons.
Novo Nordisk, which competes with Lilly with its drugs Ozympic and Vigovi, is also in the triple G game, reporting an average weight loss of nearly 20% after 24 weeks in the middle phase of another experimental drug in China last month.
The company is also pursuing other avenues, including a drug called CagriSema that combines semaglutide — the active ingredient in Ozempek and Vigovi — with cagrilintide, which targets another hormone called amylin. But in clinical trials, it hasn’t held up with lili tereseptide, much less retatretide, although Novo Nordisk is testing higher doses.
Still, while the new combinations will be “great for people who need to lose a lot of weight,” Koerner said, “not everyone needs the same big gun.”
Drugs like retatretide may be more appropriate for people with a body mass index above 45 — above 30 is considered obese — and for whom existing drugs haven’t worked well enough, Doshi said.
She estimates that about 10% of her patients either don’t get enough benefit from current medications or can’t tolerate the side effects, which are generally gastrointestinal in nature, including nausea and vomiting.
Retatrutide has shown similar side effects, as well as a burning sensation known as dysesthesia. And some participants dropped out of the RetroTide trial because they felt they had lost too much weight.
“There are cases where retatreotide will really make a difference,” Doshi said. But he worries that its souped-up results could be dangerous if it’s used improperly.
“What would happen if people took it to lose a little weight?” she asked. Already, “you’re starting to see some Hollywood portrayals of body types that are quite shocking. So there’s some concern about that.”
It’s a concern so widespread for existing drugs that Lilly released a commercial ahead of the 2024 Oscars that stressed against “void” use.
This was at a time when drug supply was a problem. “It matters who gets it,” said the ad’s tagline.
Now, supply has accelerated, including for pill versions of GLP-1s that are also changing the treatment landscape.
The Vigovi pill was approved in December, and the speed with which people began using it broke records, according to the Wall Street firm, which said it was the fastest drug launch in history. Some analysis of the uptake time shows that it stimulates at least some users who have not tried GLP-1 therapy before, suggesting that some may prefer the non-injectable option. Many new prescriptions are written by general practitioners rather than weight loss specialists.
But Vigovi pills are not expected to be alone in the market for long. Eli Lilly — continuing a nearly century-long battle with Novo Nordisk that began with insulin and has escalated with GLP-1s — expects FDA approval of its pill, orforglipron, before the end of June.
An important difference is that it can be taken at any time of the day with or without food and drink, while Vigovi pills have more restrictions. Because the latter is A version of semaglutide that is usually given by injection, it is specially formulated to be taken orally. In this way it is better than a regular pill: it should be taken first thing in the morning with a small amount of water, and no food, drink or other medication for at least 30 minutes.
For that reason, Koerner said, orforglipron would be the go-to option for people who decide they want to take a GLP-1 pill.
“If you don’t take Vigovi pills correctly, very little of the drug is absorbed,” Koerner said. “So it’s better to take that out of the equation and not worry, ‘Is my patient taking the pill correctly?'”
Cost is also an important consideration, and there, too, the weight loss pharmaceutical space has seen rapid change. The pill costs $149 a month for a low dose if patients pay out of pocket, through a deal with the Trump administration in November through the Trump Rx drug pricing initiative.
Companies also offer direct-pay rates for injectable drugs, but they still cost hundreds of dollars a month out of pocket. Still, those prices can be better for people whose insurance doesn’t cover the drug, which can still be a big problem, Douche said.
This year, Blue Cross Blue Shield of Massachusetts announced it would stop covering GLP-1 for obesity, saying the drug’s costs were driving insurance premiums too high. It recommended that patients buy drugs directly from manufacturers.
Medicare is a bright spot, expanding coverage for some patients as part of the November deal, but still not covering weight-loss drugs for everyone who might want them.
Trouble with insurance coverage is a major reason Doshi said she’s seen patients turn to Vigoi pills. And although orforglipron is expected to have a similar starting price, if there is a difference, Koerner said, that could be the deciding factor for her.
“If they’re paying out of pocket and one is less expensive than the other and I think they’re both probably better,” she said. “So I’ll change it,” she said.
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