By now, your news feed, dinner table conversations and even your doctor’s office have been buzzing about weight loss drugs like semaglutide (Ozempic) and tirzepatide (Mounjaro, Zepbound). Now, there’s a new peptide on the block: retatrutide.
All three are technically peptides, but each works slightly differently in the body. Semaglutide activates the GLP-1 receptor, while tirzepatide is a dual agonist, targeting GLP-1 and GIP (glucose-dependent insulinotropic polypeptide). Retatrutide, however, is a triple agonist, activating GLP-1, GIP and glucagon, making it a hot topic for doctors, researchers and anyone looking for more efficient weight loss.
“Think of semaglutide as a key that unlocks one lock, tirzepatide as a key that unlocks two locks and retatrutide unlocks three,” says Wajahat Mehal, M.D., director of Yale Weight Loss Program.
The internet is already buzzing with chatter: subreddits, peptide companies and stories of people sourcing research-grade chemicals from overseas. But retatrutide is still in phase 3 clinical trials and not FDA approved. Doctors caution that more research is needed before it hits the market.
READ MORE: Is There a Link Between Ozempic and Muscle Loss?
What Is Retatrutide?
“People are excited because it’s a triple agonist,” says Jyotsna Ghosh, M.D., an obesity medicine physician at Johns Hopkins Medicine.
In addition to GLP-1 and GIP, retatrutide activates glucagon, a hormone that signals the liver to break down stored sugar (glycogen).
“This can increase the energy your body burns, even at rest, and help offset the drop in metabolism that often happens after weight loss,” Dr. Ghosh explains.
Triple Agonist, More Benefits?
Early studies are promising. A phase 2 trial in The New England Journal of Medicine (2023) found that participants on a 12mg dose for 48 weeks lost an average of 24.2% of their body weight.
For context, someone starting at 118 kg with a target of 77 kg could expect:
- Semaglutide → ~95 kg
- Tirzepatide → ~94 kg
- Retatrutide → ~89 kg
“It’s likely to be recommended first for those with more weight to lose,” says Dr. Mehal. “But lower doses could help people who need less weight loss, too.”
Retatrutide is also being studied for benefits beyond weight, including reducing liver and cardiovascular risks.
Muscle Loss and Strength Training
Some speculate retatrutide might spare muscle better than semaglutide or tirzepatide. Experts say this isn’t proven: “Any extra muscle loss is just because overall weight loss is greater,” says Dr. Mehal.
Strength training and adequate protein remain essential. A new drug, bimagrumab, may eventually help reduce muscle loss further when paired with GLP-1 medications, though research is still limited.
Side Effects and Risks
So, more weight loss, more risks? Not necessarily. Retatrutide’s side effects appear similar to tirzepatide: mostly nausea and gastrointestinal symptoms, with potential increases in heart rate.
Because the drug isn’t approved yet, it’s crucial not to chase grey-market versions.
“Playing poker or dabbling in crypto is one thing, but injecting research chemicals you don’t know the origin of is another,” says Dr. Mehal.
Dr. Mehal estimates it will be at least a year before patients can access it, likely by autumn 2026. Once trials conclude, it will undergo FDA and eventually SAHPRA approval, a rigorous process that could take months.
South Africa: Skip the Fake Fixes and Stick To Real Weight Loss Drugs
While the world waits for retatrutide, South Africans already have GLP-1 medications available locally. Demand is high, which has led to opportunists selling diluted, unregulated and potentially dangerous imitations.
Dr Tommie Smook, medical practitioner at Dr Smook and Partners (managed by RXME Group), says:
“We’re seeing extraordinary transformations, with some patients losing over 150 kg using GLP-1s over one or two years — but only under proper medical supervision with lifestyle support.”
READ MORE: How to Use Your TDEE to Build Muscle, Lose Weight or Stay Lean
GLP-1 medications mimic a natural hormone released after meals that controls blood sugar, slows digestion and curbs appetite, making them powerful tools when used correctly.
10 Tips To Ensure Your GLP-1 Is Genuine
- Check licensing – Providers should be HPCSA-registered with an active dispensing licence.
- Insist on a prescription – GLP-1s are Schedule 4 drugs. No prescription = red flag.
- Verify personalised treatment – Doses must come from a compounding pharmacy registered with SAHPRA.
- Ongoing medical oversight – Regular check-ins ensure safety and effectiveness.
- Avoid online shortcuts – Unverified online sellers are risky and illegal.
- Check packaging – Legitimate products are sealed, tamper-proof and labelled with SAHPRA numbers.
- Know the source – Only licensed doctors/pharmacies can dispense.
- Side effect guidance – A proper doctor will explain and monitor side effects.
- Holistic care – Diet, exercise, and lifestyle support are critical.
- Trust your instincts – If anything feels off, walk away.
The Dangers of Black-Market Pharmaceuticals
Illegal GLP-1s can be counterfeit, expired, or improperly dosed, exposing patients to infections, allergic reactions and unpredictable blood sugar changes. Financial and privacy risks are also high.
“Without oversight, doses aren’t adjusted, progress isn’t monitored, and patients are left exposed,” says Dr. Smook. Report suspected black-market sales to SAHPRA at +27 12 313 3900.
READ MORE: NEW STUDY: Could Drinking Sparkling Water Help You Lose Weight?
Bottom Line
Retatrutide may be the next big thing in weight loss, but it’s not yet available. Until then, the safest path is talking to a licensed doctor about FDA- and SAHPRA-approved options like semaglutide or tirzepatide.
“There’s nothing shabby about the weight loss you can achieve with the GLP-1s already on the market,” says Dr. Apovian.
In other words: skip the shortcuts, trust the science, and focus on safe, sustainable results.
This article by Caitlin Carlson appeared on Men’s Health US – Additional reporting was done by the Men’s Health SA Team
