An unapproved weight loss drug is about to become available to more patients.
Retatrutide — also known as “reta” — has been shown to produce dramatically greater weight loss than blockbuster drugs like Ozempic and Mounjaro.
The experimental drug delivers a triple whammy by mimicking three hormones involved in appetite and metabolism: GLP-1, GIP and glucagon — earning the nickname “Triple G.” Most other weight loss drugs currently on the market mimic just one or two of those hormones.
In May, researchers reported that people taking retatrutide lost up to 28% of their body weight over 80 weeks, or about a year and a half.
Some participants even dropped out of a clinical trial because they lost too much weight too quickly.
For comparison, semaglutide — sold under the brand names Ozempic, Wegovy and Rybelsus) — mimics only GLP-1 and has been shown to produce roughly 15% weight loss. Tirzepatide, sold as Mounjaro and Zepbound, mimics both GLP-1 and GIP and can help patients lose around 20% of their body weight.
Retatrutide’s latest trial also found that it lowered A1C levels by up to 1.6%.
The drug’s maker, Eli Lilly, says a major aim of retatrutide is to help people with type 2 diabetes both improve blood sugar and lose weight.
“It is a struggle to achieve both … since obesity has historically been harder to treat for those with T2D,” said Dr. Kenneth Custer, Lilly’s executive vice president and cardiometabolic health president.
The company plans to submit the retatrutide for FDA approval in early 2027. If approved, the FDA’s review process could take up to a year before the drug hits the market.
Lilly guards its jewel
In the meantime, Lilly is expanding access after reports that a single 79-year-old patient obtained the retatrutide through the FDA’s “compassionate use” program, which allows some people with serious or immediately life-threatening conditions to receive investigational drugs outside of clinical trials.
After STAT reported on that case, doctors flooded in to say they had been trying to obtain the drug for their own patients but hadn’t heard a peep from Lily about who qualifies.
Now, the company is providing a bit more information. A Lilly spokesperson told Reuters that eligible patients must:
- be aged 18 or older
- have refractory obesity despite tolerating the highest approved dose of obesity therapy
- have at least two serious or life-threatening obesity-related complications for which they are receiving care.
- be unable to participate in an ongoing clinical trial of retatrutide or another investigational treatment
However, doctors say those criteria remain frustratingly vague, especially compared with other compassionate use programs that typically provide more detailed eligibility guidelines.
One study defines refractory obesity as a severe form of obesity in which a patient is unable to lose — and maintain — more than 5% of their body weight despite treatment, including the highest approved dose of weight loss medications such as semaglutide.
It’s also unclear what Lily considers a “life-threatening obesity-related complication.” Conditions such as obstructive sleep apnea, advanced liver disease, and heart failure might qualify, but the company has not specified.
To be considered, a doctor must determine that a patient meets the criteria and submit a request to Lilly. A company spokesperson said Lily is “actively reviewing requests from health care providers.”
Why classification matters
Lilly is also locked in an active dispute with the FDA over how retatrutide should be classified.
The company argues the drug is a biologic, which would grant it 12 years of market exclusivity. The FDA, however, considers it a peptide, which would provide just five years of protection.
Beyond delaying generic competition, a biologic designation would also make it more difficult for compounding pharmacies to produce alternatives — a key issue given that 1.5 million people obtain GLP-1 medications through compounded versions.
The debate comes as gray-market peptide companies are already selling their own versions of retatrutide online.
Companies typically label these products “not for human consumption” and “for research purposes only,” as their contents, potency and purity cannot be verified.
According to Public Citizen, at least 14 people have hospitalized after taking gray market versions of retatrutide.
