• Eli Lilly is developing a more potent weight-loss drug called retatrutide.
• In the first head-to-head trial versus Ozempic, retatrutide takers lost roughly twice as much weight.
• Retatrutide is not FDA-approved yet, but some peptide sellers are skirting the law.

Gym bros call it "reta." Eli Lilly is calling it the winner.

On Wednesday, the pharmaceutical giant announced the results of the first clinical trial pitting Ozempic against its newest, most powerful, and yet-to-be-approved next-generation injectable medication for obesity and diabetes: retatrutide.

Retatrutide won — and it wasn't even close. Type 2 diabetes patients on the highest dose of Ozempic (2 mg) lost an average of 21 pounds over a period of about a year and a half on the drug. Those on retatrutide lost an average of 44 pounds (9 mg) to 47 pounds (12 mg) during that same time. Patients also saw steeper reductions in their A1C, a key marker of blood sugar control (2.2% vs 1.8%).

"We believe retatrutide, if approved, could shift the treatment paradigm for people living with type 2 diabetes, obesity and related cardiometabolic conditions," Eli Lilly's Kenneth Custer, the president of Lilly Cardiometabolic, said in a release.

They're calling it 'King Kong'

Ozempic (from Novo Nordisk) was the very first medication of its kind — a novel peptide that mimics one gut hormone, called GLP-1.

Several years later, Mounjaro (from Eli Lilly) was approved, mimicking two hormones, GLP-1 and GIP, and delivering stronger results.

Insiders are calling Eli Lilly's retatrutide the "triple G" or "King Kong" for weight loss because it mimics three hormones: GLP-1, GIP, and a third peptide hormone called glucagon, which helps break down stored fat into energy. Some say it could rival bariatric surgery in clinical results in terms of weight loss.

Eli Lilly is expected to submit retatrutide to the US Food and Drug Administration for approval in early 2027. If all goes well, it could be available sometime next year, for conditions including obesity, obesity-related sleep apnea, and knee osteoarthritis.

In this clinical trial, side effect profiles were generally similar between patients taking Ozempic and retatrutide, but slightly more patients on retatrutide reported diarrhea, while constipation was slightly more common among Ozempic-takers. People on retatrutide also had slightly higher rates of a rare side effect called dysesthesia, triggering tingling, skin-on-fire type sensations.

The clinical trial results have not yet been peer-reviewed or published in a medical journal, but were released as the company prepares to announce its quarterly earnings on Thursday.

Knock-off reta is already booming on the black market

The drug, which is still in clinical trials, has attracted copycat peptide sellers shipping powders labeled "reta" from overseas, stoking a gray market of do-it-yourself injections. Bodybuilders say it helps shred fat and reduce appetite, with fewer side effects than other injectable weight-loss pens.

But nobody really knows exactly what they are taking, though their results seem to roughly mirror what happens when people take the real thing in clinical trials.

In an unusual move, Eli Lilly addressed the pre-approval black-market hype in their release announcing the latest results.

"Retatrutide is an investigational molecule that has not been approved by FDA or any regulatory organization anywhere in the world," the company said in a statement. "Anyone purporting to sell retatrutide to consumers is breaking the law."

• For decades, Accutane has been a drug of last resort for persistent acne.
• A founder who designed a new platform to streamline regulatory red tape is changing access.
• People are microdosing Accutane and reporting fewer side effects. Dermatologists have mixed views.

In the dermatology world, Accutane has a reputation as the nuclear option for bad acne.

It's the only drug that can shrink oil glands, potentially clearing pimples for good. But it comes with serious risks — primarily: a high rate of birth defects if you take it and become pregnant. Other side effects include sun sensitivity, high cholesterol, mood changes, and joint pain.

Parents are scared to put their teens on it. Dermatologists often reserve it for stubborn acne, after other creams, cleansers, antibiotics, and pills have been exhausted. And strict pregnancy-prevention rules mean monthly check-ins, tests, and blood work.

But in recent years, some of the stigma around the retinoid drug, generically called isotretinoin, has started to fade, as people have gravitated to a smaller, more strategic "Hollywood dose" of Accutane. By taking small amounts of the drug, maybe just a few days per week, many patients find they can maintain a dewy, glass-like complexion on camera while avoiding painful side effects like ultra dry skin, and the initial acne breakout purge that comes with heftier prescriptions.

"I love the Accutane glow-up," Honeydew dermatology founder David Futoran, 29, said. For him, it includes hair that's less oily, and baby-soft cheeks.

Futoran is partly responsible for turning Accutane from a maligned prescription of last resort into a buzzy internet sensation. He's found new ways to streamline and digitize paperwork, turning most of the required monthly doctor's office visits and testing for the drug into something people can do at home. Honeydew is now growing 3x year over year, Futoran said, and interest in low-dose prescriptions is increasing.

Dermatologists are divided on the trend of microdosed Accutane. Yes, it is a very effective drug, and it can clear up most breakouts. But there are tradeoffs to taking an intermittent or low-dose approach, and some doctors say why bother dancing around side effects when you could get on and off the potent drug in months, and have clear skin for life?

Founder mode for skin

Futoran founded Honeydew in 2022 after spending years on various antibiotics and multi-step cleansing and cream routines, with his acne constantly coming back.

His vision was to make prescription acne care faster and more accessible. He partnered with his longtime dermatologist, Dr. Joel Spitz, to build a telemedicine platform connecting patients with providers and treatments for acne, rosacea, eczema, and psoriasis.

Yet Futoran was still hesitant to take Accutane himself, partly because of the logistical headaches.

One morning, he said, he woke up with a large, painful cyst in the middle of his forehead. That was it, he said — he decided he was finally going on the low-dose form of Accutane his company had been prescribing.

"I should have done that from the start," he said. "My skin is way less irritated than it ever was on any of the topicals, and I just have peace because I know it works."

Accutane works because it shrinks oil glands by turning down sebum production. It triggers the death of some stem cells, which is great for clearing up overactive oil-producing glands, but very bad for developing fetuses.

In addition to making regulatory compliance digital, Honeydew offers specially formulated lip balms, cleansers, antihistamines and supplements like Omega-3 designed to replace lost oil.

Bringing a celebrity skin trick to the masses

Celebrities including Chris Pine, Pete Davidson, Emma Stone, and Kendall Jenner have all been open about using this powerful oral retinoid to help clear up persistent acne. The shadow business of microdosing Accutane, though, using it as a glow up drug even for minor, isolated breakouts, happens more through a whisper system between doctors and patients.

26-year-old marketing manager and social media influencer Kennedy Faris started microdosing Accutane with Honeydew in the spring. About a decade ago, she watched her little brother suffer some of the rarer mental health side effects of Accutane, and she was worried about the possibility the drug could lead to depression.

"My brother's a very happy person, so it was really scary," Faris told Business Insider. "I was really hesitant about starting."

After struggling to get a prescription from an in-person dermatologist, Faris heard about Honeydew from a follower and partnered with the brand. She started on a low dose of 10 milligrams, working her way up to a standard 40 mg dose over the course of a few months.

After years of trying different skincare products, antibiotics, and medications, she feels like she's finally found a more permanent solution to cystic acne. There are drawbacks to being on the drug, she said, including sensitivity to alcohol, sunlight, and some nightmares. But the real benefit has been her renewed confidence, optimism, and joy, with friends noticing she's "more bubbly and happy," she said. "I was like, 'wow, I was kind of depressed.'"

Because the drug shrinks pores, Faris has also noticed her face and nose appear slimmer.

"Everyone talks about the fake nose job," she said.

Some patients recovering from real nose jobs even use the drug to lower surgery-related inflammation and shrink pores on the nose while their face heals. As testosterone therapy booms, more men are taking Accutane to deal with oilier skin. And increasingly, patients are lining up for low-dose Accutane for minor breakouts, just to be in the clear. People are gravitating to skin treatments that will give them the edge at work and on screen, Spitz said.

"Everyone's on Zoom or Google Meets or they're on TikTok or they're on Insta, and they want to look good," he added.

The potential drawbacks of microdosing

Some doctors worry that microdosing Accutane could lead to more health complications if people stay on the medication for years at a time.

"In my practice, I just basically put people on the standard dose and then they're done at five months, and then they feel much better, Dr. Ariel Ostad, a dermatologist in Manhattan who is not affiliated with Honeydew, said. "Patients, once they go on it, their skin clears up really quickly, and they're happy, and they realize it's not as bad as they thought."

A shorter treatment course means less time worrying about drug interactions, liver or heart health, pregnancy, sun sensitivity, or bone issues.

Futoran said traditional dosing can be "absolutely the right answer for some patients," and roughly 40% of Honeydew prescriptions are at standard dosages. Still, he cites studies showing patient satisfaction is higher with low-dose Accutane, and said Honeydew patients on smaller dosages have "materially better retention."

"The best clinical outcome is when patients complete their course, but faster is not always better," he said.