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Semaglutide vs. Tirzepatide vs. Retatrutide: The Old, the Now and the Future

Oct 7
3 min read

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First there was semaglutide. Then tirzepatide raised the bar. Now everyone's whispering about retatrutide, the "triple G" shot that isn't even approved yet.


Three generations, one goal. Whether you're curious about semaglutide or comparing retatrutide vs tirzepatide, here's what the research says about each, side by side, no spin.


The old, the now and the future at a glance


Semaglutide (the old)

Tirzepatide (the now)

Retatrutide (the future)

Sold as

Wegovy, Ozempic

Zepbound, Mounjaro

Not sold yet

Hormones it mimics

GLP-1

GLP-1 + GIP

GLP-1 + GIP + glucagon

FDA status

Approved

Approved

Investigational; FDA filing expected around early 2027

Headline result

13.7% average weight loss at 72 weeks

20.2% average weight loss at 72 weeks

Up to 24.2% at 48 weeks (phase 2); up to 22.6% at 80 weeks (phase 3)


How they work (the simple version)


All three copy hormones your gut releases after a meal, which help with fullness and blood sugar. Each generation adds one more:


  • Semaglutide copies one hormone, GLP-1.

  • Tirzepatide copies two, GLP-1 and GIP.

  • Retatrutide copies three: GLP-1, GIP and glucagon. Glucagon is thought to help the body burn more energy, which is why researchers expected even bigger results.


The old vs. the now: the head-to-head trial


Semaglutide and tirzepatide are the only two that have been tested against each other directly. The SURMOUNT-5 trial, published in the New England Journal of Medicine in 2025, followed 751 adults with obesity for 72 weeks:


  • Tirzepatide: 20.2% average weight loss, about 18 cm (7 in) off the waist

  • Semaglutide: 13.7% average weight loss, about 13 cm (5 in) off the waist

  • Nearly half the tirzepatide group lost at least 20% of their body weight, compared with about a quarter on semaglutide.


The future: what we know about retatrutide


  • Phase 2 (2023): In a 48-week study of 338 adults, the highest dose led to an average 24.2% weight loss, compared with 2.1% on placebo. That number is why the internet lost its mind.

  • Phase 3 (July 2026): Two large 80-week trials reported weight loss of up to 20.8% in people with type 2 diabetes, and up to 22.6% in people with severe obesity and heart disease. Lilly says retatrutide has now had five positive phase 3 studies.

  • Side effects: Mostly digestive, like nausea and diarrhea. But more people quit because of side effects: up to 13.5% in one phase 3 trial, compared with 4.8% on placebo.


One honest caveat: these numbers come from different trials with different people and timelines, so you can't line them up as a perfect ranking. Only semaglutide vs. tirzepatide has been tested head-to-head.


The gray market: what you should know about "research only" retatrutide


No judgment here. We know retatrutide is already being sold online, long before approval. If you're curious, you deserve the full picture:


  • It's being sold as "for research use only." In August 2026, Lilly sued six sellers, alleging that label is a cover for selling to consumers. The products are typically made overseas in facilities not licensed or inspected by U.S. regulators.

  • Quality varies widely. A June 2026 investigation by the watchdog group Public Citizen found the purity and strength of unauthorized versions "varies widely."

  • People have been hospitalized. As of June 2026, FDA's adverse event system listed 14 retatrutide-related hospitalizations.

  • Influencers are often paid affiliates. Public Citizen found hundreds of social media accounts showing self-injection and linking to sellers. If someone is selling while they're "sharing," factor that in.


We're not here to tell you what to do. We're here to make sure you decide with your eyes open. The regulated options today are semaglutide and tirzepatide, through a licensed prescriber, and retatrutide is expected to reach the FDA soon.


The bottom line


  • The old still works, and it has the longest track record.

  • The now beat the old in a direct trial.

  • The future looks powerful on paper, but it isn't approved yet, and the versions sold online are a gamble on what's in the vial.


Your turn: Which of the three are you most curious about, and why? Tell us in the comments.


This post is for educational purposes only and is not medical advice. Please talk with your healthcare provider before starting, stopping or changing any medication.


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