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How Much Weight Do You Lose on GLP-1s?
GLP-1 drugs change body weight in a way that feels unusually strong and linear. Appetite falls, portions shrink, the scale moves. The pattern is simple: over 48–72 weeks, most patients on these medications lose roughly 12–15% of starting weight with semaglutide, ~18–22% with tirzepatide, and ~22–24% with retatrutide at full trial doses.
This article translates trial data into plain language: how much weight people typically lose, how much comes from fat versus muscle, and how the three drugs compare.
These numbers come from obesity and type 2 diabetes trials in supervised settings. Any decision to start, stop, or combine incretin therapies belongs with a clinician who can match these outcomes to your specific situation.
How These Drugs Work
Before comparing drugs, the basic pattern: GLP-1 drugs slow how quickly food leaves the stomach, strengthen the "enough for now" signal between gut and brain, and keep blood sugar rises smaller and smoother.
- Semaglutide — strong appetite reduction, slower nutrient appearance, some drop in energy expenditure
- Tirzepatide — similar appetite change plus more efficient insulin use (via GIP receptor) and better nutrient partitioning
- Retatrutide — appetite and insulin improvements plus preserved glucagon signalling, keeping fat oxidation high while intake falls
Comparison at a Glance
| Medication | Study | Population | Duration | Avg. Weight Loss | Fat:Lean |
|---|---|---|---|---|---|
| Semaglutide 2.4mg | STEP-1 | Obesity | 68 wk | 15% | 60:40 |
| Tirzepatide 15mg | SURMOUNT-1 | Obesity | 72 wk | 21% | 75:25 |
| Retatrutide 12mg | Phase 2 | T2D | 48 wk | 24% | 63:37 |
Important: These are from different trials with different populations and durations. Retatrutide data is Phase 2 only, in T2D patients, at 48 weeks — not directly comparable to 68-72 week obesity trials for semaglutide and tirzepatide.
Semaglutide: 12–15% Weight Loss
Semaglutide 2.4 mg once weekly is the reference point. In the STEP obesity program, patients escalated from 0.25 mg to 2.4 mg over sixteen weeks, then held at that dose.
By 68 weeks:
- Average weight loss: 12–15% of starting weight
- About 86% lost at least 5%
- Around 50% lost at least 15%
- Roughly 33% crossed 20%
For someone starting at 100 kg, that's 12–15 kg over about a year.
Dose Escalation (STEP Program)
| Dose | Weeks | Mean % Loss | Notes |
|---|---|---|---|
| 0.25 mg | 0–4 | ~1% | Early titration |
| 0.5 mg | 4–8 | 2–3% | Appetite suppression begins |
| 1.0 mg | 8–12 | 4–6% | Noticeable trajectory |
| 1.7 mg | 12–16 | 7–9% | Most reach ≥5% |
| 2.4 mg | 16–68 | 12–15% | Full effect |
Threshold Achievement (STEP-1, 68 weeks)
| Threshold | % Achieving |
|---|---|
| ≥5% | 86% |
| ≥10% | 69% |
| ≥15% | 50% |
| ≥20% | 33% |
Body Composition on Semaglutide
DXA substudy data from STEP-1:
| Component | Change | Share of Weight Lost |
|---|---|---|
| Fat mass | −19% | ~60% |
| Lean mass | −9–10% | ~40% |
Roughly 60% of the weight lost was fat, and 40% was lean mass (muscle, organ tissue, water). This pattern is common when large deficits are created quickly—the body draws from both unless the environment is biased toward muscle preservation through training and adequate protein.
Tirzepatide: 18–22% Weight Loss
Tirzepatide combines GLP-1 with GIP signalling. In SURMOUNT-1, participants escalated to 5, 10, or 15 mg once weekly over 72 weeks.
Average outcomes:
- ~15% at 5 mg
- ~19.5% at 10 mg
- ~21% at 15 mg
Dose-Dependent Loss (SURMOUNT-1, 72 weeks)
| Dose | Mean % Loss | Notes |
|---|---|---|
| 5 mg | ~15% | Entry therapeutic dose |
| 10 mg | ~19.5% | Strong effect |
| 15 mg | ~21% | Maximal studied dose |
Threshold Achievement (SURMOUNT-1)
| Threshold | 15 mg | 10 mg | 5 mg |
|---|---|---|---|
| ≥5% | >95% | >90% | ~85% |
| ≥10% | 91% | ~85% | ~70% |
| ≥15% | 83% | ~75% | ~55% |
| ≥20% | ~57% | ~40% | ~25% |
| ≥25% | ~36% | ~20% | <10% |
Body Composition on Tirzepatide
DXA substudy from SURMOUNT-1:
| Component | Change | Share of Weight Lost |
|---|---|---|
| Fat mass | −33–34% | ~75% |
| Lean mass | −8–10% | ~25% |
Tirzepatide is more selective for fat: 75% of weight lost was fat, 25% was lean mass. The GIP receptor appears to improve partitioning—more of the deficit is routed into fat depots.
Retatrutide: 22–24% Weight Loss
Retatrutide layers glucagon signalling on top of GLP-1 and GIP. In the phase 2 trial (NEJM 2023), doses ranged from 1 mg to 12 mg over 48 weeks.
At higher doses:
- ~17% at 4 mg
- ~22.8% at 8 mg
- ~24.2% at 12 mg, with no plateau at week 48
The 22–24% range in 48 weeks approaches bariatric surgery outcomes.
Dose-Dependent Loss (NEJM Phase 2, 48 weeks)
| Dose | Mean % Loss | Absolute Change | Notes |
|---|---|---|---|
| 1 mg | −8.7% | −9.4 kg | Modest response |
| 4 mg | −17.1% | −17 to −19 kg | Similar to full semaglutide |
| 8 mg | −22.8% | −24 to −26 kg | Large effect |
| 12 mg | −24.2% | −26 kg | Strongest; no plateau |
Threshold Achievement (NEJM 2023, 48 weeks)
| Dose | ≥5% | ≥10% | ≥15% |
|---|---|---|---|
| 4 mg | 92% | 75% | 60% |
| 8 mg | 100% | 91% | 75% |
| 12 mg | 100% | 93% | 83% |
At 12 mg, about a quarter of participants reached ≥30% weight loss.
Waist and Composition on Retatrutide
| Dose | Waist Reduction |
|---|---|
| 4 mg | −14.6 to −14.9 cm |
| 8 mg | −18.5 cm |
| 12 mg | −19.6 cm |
In DXA substudy (Lancet Diabetes & Endocrinology):
| Dose | Fat Mass Change |
|---|---|
| 0.5 mg | −4.9% |
| 4 mg | −15.2% |
| 8 mg | −26.1% |
| 12 mg | −23.2% |
Lean mass loss as a share of total sits in a similar 25–35% range to other GLP-1s. Higher efficacy doesn't eliminate the need to protect muscle.
The Lean Mass Problem
Body composition ratios vary by drug and population:
| Drug | Study | Population | Fat:Lean |
|---|---|---|---|
| Semaglutide 2.4mg | STEP-1 DXA | Obesity | 60:40 |
| Tirzepatide 15mg | SURMOUNT-1 DXA | Obesity | 75:25 |
| Retatrutide 8-12mg | Lancet Phase 2 | T2D | 63:37 |
Population matters: Tirzepatide shows 75:25 in non-diabetic obesity, but in T2D head-to-head studies (Clamp Study, 28 weeks), tirzepatide and semaglutide show nearly identical ratios (~87:13 vs 86:14). The GIP pathway is impaired in T2D.
Retatrutide caveat: No non-diabetic body composition data exists. The 63:37 ratio is from T2D trials only.
The numbers are not arguments against GLP-1s—they're context for why resistance training, adequate protein, and support strategies become non-optional for patients who care about body composition.
Why Lean Mass Drops
- Appetite suppression lowers protein intake unless you plan around it
- Lower energy and sedentary time dampen training volume and anabolic signals
- Multi-agonists drive high fat flux — if mitochondrial capacity lags, muscle becomes collateral
Why Some People Feel Worse as Numbers Improve
Patients often describe a mismatch: charts look better, but energy feels worse. Lighter, but exhausted.
Part of the mismatch is composition. When 25–40% of loss comes from lean mass, you shed muscle that was carrying metabolic load. The result is a more fragile system.
Another part is how the deficit is created. GLP-1s suppress intake but don't specify which tissue pays the bill. Unless the environment is biased toward preserving muscle — through training, protein, and sometimes support compounds — the body chooses the convenient combination of fat and lean.
What These Numbers Don't Tell You
The trials have specific inclusion criteria: BMI thresholds, comorbidities, exclusion rules. People taking GLP-1s in practice often differ in age, training status, ethnicity, and metabolic architecture.
A few boundaries:
- Severe obesity and high-risk cardiometabolic profiles were the primary settings — translating to lower-BMI or highly trained individuals isn't straightforward
- Time frame matters — most percentages are 48–72 week endpoints
- Maintenance is its own problem — many studies include structured support; discontinuation patterns depend on what happens after
Protecting Lean Mass
Three levers consistently show up:
- Protein first — at least 1.6 g/kg daily, distributed across meals
- Minimum-effective resistance training — 2–3 full-body sessions weekly with challenging loads
- Support strategies — in clinical settings, teams often pair GLP-1s with compounds that protect lean tissue and support energy
For protocol-level detail, see:
Summary
- GLP-1 drugs reliably produce double-digit weight loss in trial settings
- Semaglutide: 12–15%, tirzepatide: 18–22%, retatrutide: 22–24% at higher doses
- Most of that change is fat, but 25–40% is lean mass without countermeasures
- Waist and visceral fat reduction are large contributors to metabolic improvement
- None of these numbers replace clinical judgment or the need to protect muscle
Related Guides
- Complete GLP-1 Comparison — mechanism and side-effect comparison
- Semaglutide Guide — detailed semaglutide overview
- Tirzepatide Guide — detailed tirzepatide overview
- Retatrutide Guide — investigational triple-agonist
References
- Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). NEJM 2021. https://doi.org/10.1056/NEJMoa2032183
- Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). NEJM 2022. https://doi.org/10.1056/NEJMoa2206038
- Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity. NEJM 2023. https://doi.org/10.1056/NEJMoa2301972
Medical Disclaimer
The content in this GLP-1 results guide is for informational purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider before beginning any new protocol, supplement, or medication.