How Much Weight Do You Lose on GLP-1s?
GLP-1–based drugs change body weight in a way that feels unusually strong and linear. Appetite falls, portions shrink, the scale moves. Underneath, 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. These are averages from large clinical trials, not guarantees for any individual.
This article translates those trial tables into plain language: how much weight people typically lose, how much comes from fat versus muscle, and how semaglutide, tirzepatide, and retatrutide compare when used as obesity drugs rather than lifestyle trims.
Medical context
- This piece is educational. It does not recommend any drug or stack.
- Numbers below 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 a specific patient and monitor for risk.
The underlying trial tables and body-composition data live in the GLP‑1 / GIP / glucagon incretin results backbone in the research notes. This article sits on top of that backbone and keeps the numbers intact while making them easier to read.
1. How These Drugs Work at a High Level
Before comparing drugs, it helps to hold the basic pattern in view. GLP‑1 drugs do three things at once: they slow how quickly food leaves the stomach, they strengthen the “enough for now” signal between gut and brain, and they keep blood sugar rises smaller and smoother. The technical label for this triad is incretin signalling, dominated by the GLP‑1 (glucagon‑like peptide‑1) pathway.
Semaglutide is a strong GLP‑1 signal on its own. Tirzepatide adds a second signal called GIP, which refines how insulin is used. Retatrutide adds a third signal through the glucagon receptor, which keeps the liver burning fat rather than letting energy expenditure fall. The result is three related but distinct metabolic postures:
- Semaglutide — strong appetite reduction, slower nutrient appearance, some drop in energy expenditure.
- Tirzepatide — similar appetite change plus more efficient insulin use and better partitioning of where calories go.
- Retatrutide — appetite and insulin improvements plus preserved glucagon signalling, keeping fat oxidation high while intake falls.
1.1 High‑level comparison at a glance
| Medication | Max Dose | Avg. Weight Loss | Fat Share of Weight Lost | Lean Share | Waist Reduction |
|---|---|---|---|---|---|
| Semaglutide | 2.4 mg | 12–15% | ~60% | ~40% | 9–11 cm |
| Tirzepatide | 15 mg | 18–22% | ~75% | ~25% | 14–17 cm |
| Retatrutide | 12 mg | 22–24% | ~70% (est.) | ~30% | 15–20 cm |
These figures are population averages from obesity trials. Individual responses are wider, but this table captures the centre of gravity for each drug when pushed to full trial doses.
The rest of this article looks at what that means in numbers: how much weight leaves, what share is fat, and how the drugs compare.
2. Semaglutide: What 12–15% Weight Loss Looks Like
Semaglutide 2.4 mg once weekly is the reference point most people now have in mind. In the STEP obesity program, patients were slowly escalated from 0.25 mg up to 2.4 mg over sixteen weeks, then held at that dose out to about a year.
By 68 weeks:
- Average weight loss settled around 12–15% of starting weight at the full 2.4 mg dose.
- About 86% of patients lost at least 5% of their weight.
- Around 50% lost at least 15%, and roughly a third crossed the 20% mark.
In practical terms, for someone starting at 100 kg, the average pattern looked like a 12–15 kg reduction over a little more than a year, with about half of patients landing in the 15 kg or higher range.
2.1 Semaglutide trial tables
Dose escalation and average weight loss (STEP program)
| Dose Stage | Weeks on Dose | Mean % Weight Loss | Notes |
|---|---|---|---|
| 0.25 mg | 0–4 | ~1% | Early titration phase |
| 0.5 mg | 4–8 | 2–3% | Appetite suppression begins |
| 1.0 mg | 8–12 | 4–6% | Noticeable weight trajectory |
| 1.7 mg | 12–16 | 7–9% | Most reach ≥5% loss |
| 2.4 mg (maintenance) | 16–68 | 12–15% | Full therapeutic effect |
How many people hit each threshold (STEP‑1, 68 weeks)
| Threshold | Percentage Achieving |
|---|---|
| ≥5% | 86% |
| ≥10% | 69% |
| ≥15% | 50% |
| ≥20% | 33% |
These numbers are drawn directly from the STEP clinical program and the STEP‑1 obesity trial, which used once‑weekly semaglutide 2.4 mg in adults with obesity or overweight plus comorbidities.
2.2 What Comes Off: Fat vs Muscle on Semaglutide
Body-composition scans show that the weight change is not pure fat. DXA substudy data from STEP‑1 found that fat mass fell by about 19%, while lean mass fell by 9–10%.
Body composition on semaglutide (STEP‑1 DXA substudy)
| Component | Percent Change | Share of Total Weight Lost |
|---|---|---|
| Fat mass | −19% | ~60% |
| Lean mass | −9–10% | ~40% |
Put differently:
- Roughly 60% of the weight lost was fat mass.
- Roughly 40% of the weight lost was lean mass, which includes muscle, organ tissue, and water inside those compartments.
That 40% share is not unique to semaglutide. It is a common pattern when large deficits are created quickly, whether by medication, surgery, or extreme dieting. The drug lowers intake; the body defends itself by drawing from both fat and lean tissue unless the environment is actively biased toward muscle preservation through resistance training and adequate protein.
3. Tirzepatide: Pushing into the 20% Range
Tirzepatide combines GLP‑1 signalling with GIP in a single molecule. In the SURMOUNT‑1 trial, participants were escalated to 5 mg, 10 mg, or 15 mg once weekly and followed for 72 weeks.
Average outcomes:
- ~15% weight loss at 5 mg.
- ~19.5% weight loss at 10 mg.
- ~21% weight loss at 15 mg.
3.1 Tirzepatide trial tables
Dose‑dependent average weight loss (SURMOUNT‑1, 72 weeks)
| Dose | Mean % Weight Loss | Notes |
|---|---|---|
| 5 mg | ~15% | Entry therapeutic dose |
| 10 mg | ~19.5% | Strong effect |
| 15 mg | ~21% | Maximal studied dose |
Response rates at the highest dose were striking:
- More than 95% of people lost at least 5% of their weight.
- About 91% crossed the 10% threshold.
- Around 83% lost at least 15%.
- 57% reached 20% or more weight loss, and over a third crossed 25%.
How many people reached each threshold (SURMOUNT‑1)
| Threshold | 15 mg Dose | 10 mg Dose | 5 mg Dose |
|---|---|---|---|
| ≥5% | >95% | >90% | ~85% |
| ≥10% | 91% | ~85% | ~70% |
| ≥15% | 83% | ~75% | ~55% |
| ≥20% | ~57% | ~40% | ~25% |
| ≥25% | ~36% | ~20% | <10% |
Compared to semaglutide, tirzepatide pushes more of the population into higher loss bands, and a larger share of participants experience “bariatric‑like” changes in the 20–25% range.
3.2 Tirzepatide and Body Composition
DXA substudy data from SURMOUNT‑1 show that tirzepatide is more selective for fat than semaglutide:
- Fat mass fell by about 33–34%.
- Lean mass fell by about 8–10%.
Body composition on tirzepatide (SURMOUNT‑1 DXA substudy)
| Component | Percent Change | Share of Total Weight Lost |
|---|---|---|
| Fat mass | −33–34% | ~75% |
| Lean mass | −8–10% | ~25% |
When expressed as a share of weight lost:
- Roughly 75% of the weight lost was fat mass.
- Roughly 25% was lean mass.
The difference is not that muscle loss disappears; it is that more of the deficit is routed into fat depots, and less is paid for by lean tissue.
4. Retatrutide: The Current Upper End of Trial Data
Retatrutide layers glucagon signalling on top of GLP‑1 and GIP. In the phase 2 obesity trial published in 2023, weekly doses ranged from 1 mg up to 12 mg over 48 weeks.
At 1 mg, weight loss was modest (~8–9%). At higher doses:
- ~17% average weight loss at 4 mg.
- ~22.8% average weight loss at 8 mg.
- ~24.2% average weight loss at 12 mg, with no clear plateau at the end of the study window.
For context, that 22–24% range in 48 weeks is similar to, or exceeds, what many people see after bariatric surgery, though the mechanisms and patient selection differ.
Response rates at higher doses:
- At 8–12 mg, almost everyone reached at least 5% loss.
- Around 75–83% reached at least 15% loss by week 48.
- In the 12 mg group, about a quarter of participants reached 30% or more weight loss.
4.1 Retatrutide trial tables
Dose‑dependent average weight loss (NEJM phase 2, 48 weeks)
| Dose | Mean % Weight Loss (48 weeks) | Least-Squares Mean Change | Notes |
|---|---|---|---|
| 1 mg | −8.7% | −9.4 kg | Modest response |
| 4 mg | −17.1% | −17.3 to −19.1 kg | Similar to full semaglutide |
| 8 mg | −22.8% | −23.5 to −25.9 kg | Large effect |
| 12 mg | −24.2% | −26.2 kg | Strongest response; no plateau reached |
How many people reached each threshold (NEJM 2023, 48 weeks)
| Dose | ≥5% | ≥10% | ≥15% |
|---|---|---|---|
| 4 mg | 92% | 75% | 60% |
| 8 mg | 100% | 91% | 75% |
| 12 mg | 100% | 93% | 83% |
At the top dose, roughly a quarter of participants also crossed the 30% weight‑loss mark by week 48.
Retatrutide remains investigational. These figures describe what has been observed under trial conditions and should not be treated as reachable targets in routine clinical practice without careful supervision.
4.2 Retatrutide, Waist, and Body Composition
Waist measurements and DXA scans provide a clearer picture of how that weight change is distributed.
- Waist circumference shrank by roughly 15–20 cm at the higher doses, a signal of deep visceral fat loss.
- In a separate DXA substudy in type 2 diabetes:
- Fat mass fell by 15–26% depending on dose.
- Lean mass loss as a share of total weight change sat in a similar 25–35% range to semaglutide and tirzepatide.
Waist circumference reductions (NEJM 2023 trial)
| Dose | Change (cm) |
|---|---|
| 4 mg | −14.6 to −14.9 cm |
| 8 mg | −18.5 cm |
| 12 mg | −19.6 cm |
Body composition on retatrutide (Lancet Diabetes & Endocrinology DXA substudy)
| Dose | Fat Mass Change (%) | Notes |
|---|---|---|
| 0.5 mg | −4.9% | Minimal effect |
| 4 mg | −15.2% | Significant fat reduction |
| 8 mg | −26.1% | Largest fat loss |
| 12 mg | −23.2% | Near-maximal |
The pattern is similar to tirzepatide: most weight lost is fat, but a non‑trivial share remains lean tissue. Raising efficacy does not remove the need to protect muscle; it makes that work more important.
For a deeper mechanistic discussion of retatrutide’s triple‑agonist design and its role as a metabolic foundation, see the retatrutide peptide card in the content library.
5. How Much of the Weight Is Fat vs Muscle?
Across these three drugs, the common signal is that most of the lost weight is fat, but a meaningful fraction is lean mass:
- Semaglutide: about 60% fat / 40% lean share of weight lost.
- Tirzepatide: about 75% fat / 25% lean.
- Retatrutide: estimated 70% fat / 30% lean, based on trial and substudy statements.
Clinical reviews of GLP‑1–based therapies more broadly report that roughly 25–40% of weight lost in these settings often comes from lean mass. That variability depends on baseline muscle, age, sex, training status, and diet.
Lean mass loss has direct consequences: lower strength, reduced metabolic flexibility, and a smaller buffer for future metabolic load. The numbers above are not arguments against GLP‑1s; they are the context in which resistance training, adequate protein intake, and adjuncts that support lean tissue become non‑optional for patients who care about body composition, not just the scale.
6. Waist, Shape, and Where the Fat Leaves
Scale weight is crude. Waist and regional fat tell more of the story.
- Semaglutide reduced waist circumference by roughly 9–11 cm at full trial doses.
- Tirzepatide narrowed waists by about 14–17 cm at higher doses.
- Retatrutide tended to reduce waist by 15–20 cm, reflecting deeper visceral fat clearance.
These are ballpark figures from the major obesity trials. The pattern is that stronger therapies drive larger waist reductions, signalling more aggressive removal of fat from the visceral compartment, the liver, and surrounding organs. This is a major contributor to improvements in insulin resistance, blood pressure, and inflammatory tone seen in the same studies.
7. Why Some People Feel Worse Even as the Numbers Improve
Patients often describe a mismatch: charts look better, but energy feels worse. The system is lighter, yet training feels harder and day‑to‑day resilience declines.
Part of that mismatch is the composition of the weight loss. When 25–40% of the change comes from lean mass, the body sheds not just excess fat but also muscle fibres that were previously helping carry metabolic load. The result can be a more fragile system: lower strength, slower recovery, and a narrower margin for error when life becomes stressful or sedentary.
Another part is how the deficit is created. GLP‑1 monotherapies suppress intake and slow gastric emptying. They create pressure but do not, by themselves, specify which tissue should pay the bill. Unless the environment is biased toward preserving muscle — through training, protein, and sometimes adjunct therapies — the body chooses the convenient combination of fat and lean tissue.
More advanced architectures, such as dual‑axis recomposition stacks, try to route that pressure differently by aligning appetite control with preserved fat oxidation and anabolic support. Those belong in protocol and stack notes. Here, the point is simpler: the more strongly a drug lowers intake, the more deliberate the plan has to be for maintaining muscle and performance.
8. Who These Numbers Apply To — And Who They Do Not
The trials behind these numbers have specific inclusion criteria: BMI thresholds, comorbidities, prior treatment history, and exclusion rules for organ disease and other risks. People taking GLP‑1s in everyday practice often differ from those trial cohorts in age, training status, ethnicity, and background metabolic architecture.
A few practical boundaries:
- Severe obesity and high-risk cardiometabolic profiles were the primary settings for these studies; translating outcomes to lower‑BMI, highly trained, or sarcopenic individuals is not straightforward.
- Time frame matters. Most headline percentages are 48–72 week endpoints; shorter runs will show smaller changes, and extended runs may change the curve again.
- Maintenance is its own problem. Many studies include structured lifestyle support and close follow‑up; discontinuation and weight regain patterns depend heavily on what happens after the drug is stopped or tapered.
For clinicians, the trial figures are reference points, not promises. For patients, they are a way to calibrate expectations and understand why two people on the same drug can land in very different places.
9. Safety, Monitoring, and Where to Go Next
This article has focused on efficacy. The risk architecture — gastrointestinal load, gallbladder risk, pancreatitis concerns, retinopathy flares in rapid glucose improvement, and lean-mass decline — is equally important.
Monitoring frameworks for GLP‑1 therapy typically track:
- Lean mass and strength over time.
- Glycaemic markers, lipids, liver enzymes, and renal function.
- Symptoms that signal over‑rapid loss or intolerance (persistent nausea, dehydration, visual changes, severe fatigue).
Those monitoring details, red‑flag domains, and the evidence behind them are developed in the GLP‑1 cases and clinical monitoring notes in the research section. Protocol‑level architectures, including dual‑axis recomposition stacks that use retatrutide and support layers to prioritise body composition, are discussed separately.
For this article, the key points are straightforward:
- GLP‑1–based drugs reliably produce double‑digit percentage weight loss in trial settings.
- Semaglutide sits around 12–15%, tirzepatide around 18–22%, and retatrutide around 22–24% at higher doses.
- Most of that change is fat, but 25–40% is lean mass unless deliberate countermeasures are in place.
- Waist and visceral fat reduction are large contributors to risk reduction.
- None of these numbers replace clinical judgement or the need to protect muscle, function, and long‑term metabolic capacity.