Comparison · Fat loss

Retatrutide vs Semaglutide vs Tirzepatide.

Three of the most studied metabolic peptides for weight loss, compared side by side — how each one works, what the clinical trials found, how they're dosed, and where they stand on approval. Sourced, honest, and built for research context.

The short answer

All three are injectable metabolic peptides that suppress appetite through gut-hormone pathways. Semaglutide is a single GLP-1 agonist, tirzepatide a dual GIP/GLP-1 agonist, and retatrutide a triple GIP/GLP-1/glucagon agonist. In separate trials, average weight loss rose with each newer molecule — roughly 15%, 21% and 24% of body weight respectively.

Last updated: July 2026 · For research use only · Not medical advice

Side by side

The comparison, at a glance.

  Semaglutide Tirzepatide Retatrutide
Drug class GLP-1 receptor agonist Dual GIP / GLP-1 agonist Triple GIP / GLP-1 / glucagon agonist
Receptor targets GLP-1 GIP + GLP-1 GIP + GLP-1 + glucagon
Mean weight loss (trial) ~14.9% at 68 wks ~20.9% at 72 wks ~24.2% at 48 wks
Highest dose studied 2.4 mg / week 15 mg / week 12 mg / week
Key trial STEP 1 (NEJM 2021)1 SURMOUNT-1 (NEJM 2022)2 Phase 2 (NEJM 2023)3
Dosing Once weekly, titrated Once weekly, titrated Once weekly, titrated
Approval status (2026) Approved (Wegovy / Ozempic) Approved (Zepbound / Mounjaro) Investigational (phase 3)
At Novapep Semaglutide — from €75 Tirzepatide — from €75 Retatrutide — from €98

Figures come from three separate clinical trials with different populations and durations, so they are indicative — not a direct head-to-head comparison.

In detail

Semaglutide

Semaglutide is a GLP-1 receptor agonist that mimics the gut hormone GLP-1, slowing gastric emptying and reducing appetite. In the STEP 1 trial, adults on 2.4 mg weekly lost a mean of 14.9% of body weight over 68 weeks, versus 2.4% on placebo.1

  • Single-pathway mechanism — the most established of the three, with the longest real-world safety record.
  • Approved for chronic weight management (Wegovy) and type 2 diabetes (Ozempic).
  • Most common side effects are gastrointestinal (nausea, diarrhoea), typically worst during titration.
View semaglutide →

Tirzepatide

Tirzepatide is a dual agonist that activates both GIP and GLP-1 receptors. Adding GIP appears to improve metabolic effect: in SURMOUNT-1, participants on 15 mg weekly lost a mean of 20.9% of body weight over 72 weeks, versus 3.1% on placebo.2

  • Dual-pathway mechanism — greater average weight loss than semaglutide in trials.
  • Approved for chronic weight management (Zepbound) and type 2 diabetes (Mounjaro).
  • Side-effect profile similar to semaglutide, predominantly gastrointestinal.
View tirzepatide →

Retatrutide

Retatrutide is a triple agonist targeting GIP, GLP-1 and glucagon receptors. The glucagon activity is thought to raise energy expenditure on top of appetite suppression. In a phase 2 trial, adults on 12 mg weekly lost a mean of 24.2% of body weight at 48 weeks.3

  • Triple-pathway mechanism — the largest average weight loss reported so far, though from earlier-stage (phase 2) data.
  • Investigational — not yet approved by any regulator; phase 3 trials are ongoing as of 2026.
  • Long-term safety data is more limited than for semaglutide and tirzepatide.
View retatrutide →
Choosing

How to think about the choice.

Track record vs. magnitude. Semaglutide has the longest safety record; tirzepatide offers greater average weight loss with a comparable, well-characterised profile; retatrutide shows the largest effect in early data but is still investigational with less long-term safety evidence.

Individual response varies widely. Trial averages hide a wide spread — some people respond far more or less than the mean. Starting dose, titration speed and tolerance to gastrointestinal effects all matter.

This is not a prescribing decision to make alone. These are potent metabolic compounds. Novapep builds protocols around your medical exams and always recommends working with a qualified clinician.

FAQ

Common questions.

Which is strongest for weight loss?

In trial data, average weight loss increased with each newer molecule: semaglutide ~15% (STEP 1), tirzepatide ~21% (SURMOUNT-1), retatrutide ~24% (phase 2). These are separate trials, so the figures are indicative rather than a direct head-to-head result.

What's the difference in how they work?

Semaglutide activates one receptor (GLP-1), tirzepatide activates two (GIP + GLP-1), and retatrutide activates three (GIP + GLP-1 + glucagon). More pathways broadly correlate with greater average effect in the trials to date.

Are they approved medicines?

Semaglutide (Wegovy, Ozempic) and tirzepatide (Zepbound, Mounjaro) are approved by regulators including the FDA. Retatrutide is investigational and, as of 2026, not approved. Novapep supplies all three for research use only.

How are they dosed?

All three were studied as once-weekly subcutaneous injections with gradual dose escalation (titration) to limit gastrointestinal side effects.

What are the main side effects?

Predominantly gastrointestinal — nausea, diarrhoea, vomiting, constipation — usually most pronounced during titration. This is educational information, not medical advice; consult a qualified clinician before use.

Sources
  1. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384:989–1002. nejm.org/doi/full/10.1056/NEJMoa2032183
  2. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387:205–216. nejm.org/doi/full/10.1056/NEJMoa2206038
  3. Jastreboff AM, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389:514–526. nejm.org/doi/full/10.1056/NEJMoa2301972

Important. This page is an educational comparison of published research. It is not medical advice, a treatment recommendation, or a claim of therapeutic benefit. Semaglutide, tirzepatide and retatrutide are prescription-only or investigational medicines in their approved contexts. All products supplied by Novapep are lab-tested and intended for research use only, not for human or veterinary consumption. Always consult a qualified healthcare professional before considering any compound.

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