Phase 2 Clinical Trial • Jastreboff et al., NEJM 2023

Retatrutide Before and After: What the Clinical Data Shows

By MeetPeptide Research Team

Last updated: March 2026

Retatrutide Phase 2 data shows participants lost an average of 24.2% of body weight at the highest dose (12mg) over 48 weeks — roughly 58 lbs for a 240-lb person — with no plateau observed, suggesting even greater loss with longer treatment.

Real weight loss results from the Phase 2 trial of retatrutide (LY3437943) — the triple-agonist that produced up to 24.2% body weight loss in 48 weeks.

0%
Max Weight Loss
0 wk
Study Duration
0
Participants
48-Week Results

Retatrutide Weight Loss by Dose

Percent change in body weight at 48 weeks across all dose groups. Data from the Phase 2 trial (NCT04881760).

Placebo
−2.1%
1 mg
−8.7%
4 mg (fixed)
−12.9%
4 mg (escalated)
−17.1%
8 mg
−22.8%
12 mg
−24.2%
Weight Loss Timeline

How Fast Does Retatrutide Work?

Percent body weight change at key timepoints (24 and 48 weeks) across dose groups. These are the reported timepoints from the Phase 2 trial.

At 24 Weeks
Placebo
−2.0%
1 mg
−6.0%
4 mg (esc.)
−11.0%
8 mg
−17.0%
12 mg
−19.0%
At 48 Weeks (Final)
Placebo
−2.1%
1 mg
−8.7%
4 mg (esc.)
−17.1%
8 mg
−22.8%
12 mg
−24.2%

Note: Approximate 24-week values read from published trial figures. Exact interim timepoints beyond 24 and 48 weeks were not separately reported in the primary publication.

Before & After by the Numbers

What Retatrutide Results Look Like in Real Weight

Based on trial averages applied to an example starting weight of 220 lbs (100 kg). Individual results vary.

Dose Group % Lost at 24 wk Weight at 24 wk % Lost at 48 wk Weight at 48 wk Total lbs Lost
Placebo −2.0% 215.6 lbs −2.1% 215.4 lbs 4.6 lbs
1 mg −6.0% 206.8 lbs −8.7% 200.9 lbs 19.1 lbs
4 mg (escalated) −11.0% 195.8 lbs −17.1% 182.4 lbs 37.6 lbs
4 mg (fixed) — — −12.9% 191.6 lbs 28.4 lbs
8 mg −17.0% 182.6 lbs −22.8% 169.8 lbs 50.2 lbs
12 mg −19.0% 178.2 lbs −24.2% 166.8 lbs 53.2 lbs

Starting weight: 220 lbs (100 kg). "Weight at X wk" = 220 × (1 − % lost). These are averages — individual results vary significantly.

How It Compares

Retatrutide vs. Tirzepatide vs. Semaglutide

Peak weight loss across three landmark clinical trials. Different study durations — see caveat below.

Most Weight Loss
Retatrutide
12 mg weekly
−24.2%
48 weeks
Jastreboff et al., NEJM 2023 (Phase 2)
Tirzepatide
15 mg weekly
−22.5%
72 weeks
SURMOUNT-1, Jastreboff et al., NEJM 2022
Semaglutide
2.4 mg weekly
−14.9%
68 weeks
STEP 1, Wilding et al., NEJM 2021
⚠️ Cross-trial comparison caveat: These results come from different trials with different durations, patient populations, and study designs. Retatrutide's result is from a Phase 2 trial (48 weeks), while tirzepatide and semaglutide data are from Phase 3 trials (72 and 68 weeks). Direct comparison requires head-to-head studies, which have not yet been conducted.
Body Composition

Fat Loss vs. Lean Mass

The Phase 2 trial reported that the majority of weight lost was fat mass. Detailed body composition data from the highest-dose groups:

~78%
Fat Mass Lost
of total weight lost
~22%
Lean Mass Lost
of total weight lost

Body composition was assessed as a secondary endpoint. The fat-to-lean mass loss ratio is consistent with other GLP-1 receptor agonist trials. Detailed sub-group breakdowns were limited in the Phase 2 publication. Resistance training during weight loss can help preserve lean mass.

Side Effects Reality Check

Most Common Adverse Events

Reported in the 12 mg dose group. Most side effects were mild-to-moderate and decreased over time with dose escalation.

Nausea
~45%
Diarrhea
~34%
Vomiting
~18%
Constipation
~16%
Decreased appetite
~22%
Dyspepsia
~10%

Approximate percentages from the 12 mg escalated dose group. Gastrointestinal events were the most common reason for discontinuation. Dose escalation schedules reduced GI side effect severity.

What to Expect

Retatrutide Weight Loss Timeline

General phases observed in the clinical trial, based on the weight loss trajectory in the higher-dose groups.

Week 1–4
Adjustment Phase
Dose escalation begins. GI side effects most common early on. Weight loss starts but is modest (1–3%). Body adjusts to the medication.
Week 4–12
Acceleration
Appetite suppression strengthens. Weight loss accelerates as doses increase. Participants in the 12 mg group lost roughly 7–10% by this phase.
Week 12–24
Peak Loss Rate
The steepest weight loss trajectory. 12 mg group approaching ~19% loss. GI side effects typically improving by this phase.
Week 24–48
Continued Progress
Weight loss continues but rate gradually slows as the body approaches a new equilibrium. Final results: up to 24.2% at 48 weeks. Curve was still declining at study end.
Key Takeaways

Retatrutide Before and After — The Bottom Line

✅ What We Know

  • The 12 mg dose produced 24.2% mean body weight loss in 48 weeks — the highest ever reported for an obesity drug at the time
  • Clear dose-response: higher doses produced more weight loss
  • Weight was still declining at 48 weeks (the study hadn't plateaued)
  • Majority of weight lost (~78%) was fat mass, not lean mass
  • GI side effects are common but mostly mild-to-moderate and improve over time
  • Triple-agonist mechanism (GIP + GLP-1 + Glucagon) differentiates it from existing drugs
  • Phase 3 trials (TRIUMPH program) are underway for more definitive data

⚠️ What We Don't Know

  • Long-term safety beyond 48 weeks is unproven — Phase 3 trials are ongoing
  • What happens after discontinuation (weight regain is expected based on other GLP-1 drugs)
  • Cardiovascular outcomes data (no CVOT completed yet)
  • How it compares head-to-head vs tirzepatide or semaglutide
  • Optimal dosing — the 8 mg and 12 mg groups had similar GI side effect rates
  • Effects on specific populations (no data on older adults, T2D-specific outcomes, etc.)
  • FDA approval timeline — still investigational, not approved for any indication
Track Your Progress

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Disclaimer: This page is for educational and informational purposes only. It is not medical advice. Retatrutide (LY3437943) is an investigational drug not approved by the FDA. "Before and after" data represents clinical trial averages — individual results vary significantly. Always consult with a qualified healthcare provider. Data sourced from Jastreboff et al., N Engl J Med 2023; 389:514-526. ClinicalTrials.gov: NCT04881760.

Frequently Asked Questions

What does retatrutide weight loss look like?

Phase 2 clinical trial data shows that participants on retatrutide 12mg lost an average of 24.2% of their body weight over 48 weeks — translating to roughly 58 lbs for a 240-lb person. The weight loss was progressive, continuing throughout the trial without plateauing, which is unusual compared to other obesity medications.

How fast do you lose weight on retatrutide?

In Phase 2 trials, weight loss began within the first 4 weeks and continued progressively throughout the 48-week study period. Participants at the 12mg dose lost approximately 2–3% of body weight per month during peak treatment. Unlike some other GLP-1 drugs, retatrutide's weight loss curve showed no significant plateau by week 48, suggesting continued loss with longer treatment.

Is retatrutide better than semaglutide?

Based on Phase 2 clinical data, retatrutide produced significantly greater weight loss (24.2%) than semaglutide (approximately 14.9% in comparable trials) — roughly 60% more weight loss. Retatrutide's triple agonist mechanism (GIP/GLP-1/Glucagon) appears more powerful than semaglutide's single GLP-1 mechanism. However, head-to-head trials have not been conducted, and retatrutide is not yet FDA-approved.