GLP-1 Weight Loss Calculator,
based on clinical trial data.

Clinical trial guide

GLP-1 weight loss: what the STEP and SURMOUNT trials actually showed

What are GLP-1 receptor agonists?

GLP-1 (glucagon-like peptide-1) receptor agonists are a class of injectable medications originally developed for type 2 diabetes management. They work by mimicking a naturally occurring gut hormone that regulates blood sugar and appetite. When bound to GLP-1 receptors in the pancreas, brain, and gut, they slow gastric emptying, reduce appetite, and increase feelings of satiety — leading to significant weight reduction in clinical trials.

Two GLP-1 medications have received FDA approval specifically for chronic weight management (obesity):

• Semaglutide (Wegovy): a weekly subcutaneous injection at 2.4 mg. Ozempic is the same molecule at lower doses (0.5–2 mg) for diabetes, and is sometimes prescribed off-label for weight loss.
• Tirzepatide (Zepbound): a weekly subcutaneous injection that is a dual GIP/GLP-1 receptor agonist. Mounjaro is the same molecule at lower doses for diabetes.

The STEP 1 trial: semaglutide 2.4 mg vs. placebo

The STEP 1 trial (NCT03548935) was a 68-week randomized, double-blind, placebo-controlled trial published in the New England Journal of Medicine in 2021 (Wilding et al.). 1,961 adults with a BMI ≥ 30 (or ≥ 27 with at least one weight-related condition) were randomized to weekly subcutaneous semaglutide 2.4 mg or placebo, alongside lifestyle intervention.

Key findings:

• Mean weight loss: 14.9% of body weight in the semaglutide group vs. 2.4% with placebo — a net difference of 12.4 percentage points.
• Responder rates: 86.4% of semaglutide participants lost ≥ 5% body weight; 69.1% lost ≥ 10%; 50.5% lost ≥ 15%.
• Timeline: Maximum weight loss was approached by approximately week 60–68, with the steepest reduction occurring in the first 24 weeks.
• Side effects: Nausea (44%), diarrhea (30%), vomiting (25%), and constipation (24%) were the most common. Most gastrointestinal effects were transient, occurring during dose escalation.

The SURMOUNT-1 trial: tirzepatide vs. placebo

The SURMOUNT-1 trial (NCT04184622) was a 72-week randomized, double-blind, placebo-controlled trial published in the New England Journal of Medicine in 2022 (Jastreboff et al.). 2,539 adults with BMI ≥ 30 (or ≥ 27 with a weight-related condition) were randomized to tirzepatide (5 mg, 10 mg, or 15 mg) or placebo weekly.

Key findings for the 15 mg (highest) dose:

• Mean weight loss: 20.9% of body weight vs. 3.1% with placebo — a net difference of 17.8 percentage points. This is substantially greater than semaglutide's effect.
• Responder rates (15 mg): 91% lost ≥ 5%; 79% lost ≥ 10%; 57% lost ≥ 20% of body weight.
• The dual-agonist advantage: Tirzepatide binds both GIP and GLP-1 receptors, which may explain its greater weight-loss efficacy. GIP additionally promotes fat cell metabolism and may reduce the nausea associated with pure GLP-1 activation.
• Side effects: Similar profile to semaglutide — nausea, diarrhea, vomiting, and constipation — with comparable rates.

How this calculator models weight loss curves

The projected weight curves are derived from the published mean weight loss data points at each scheduled visit (approximately every 4 weeks) in the STEP 1 and SURMOUNT-1 trials. Between these data points, the calculator uses linear interpolation to estimate intermediate values.

The weight loss trajectory follows a characteristic pattern across both medications:

• Rapid initial phase (weeks 0–24): Weight loss is steepest as appetite suppression is at its peak and patients adapt to the medication.
• Slower mid-phase (weeks 24–52): The rate of weight loss decelerates as the body adapts metabolically and caloric intake stabilizes at a new set point.
• Plateau (weeks 52–68/72): Weight loss approaches its maximum and stabilizes. Some patients continue to lose slowly; others maintain rather than continue declining.

Factors that affect individual outcomes

Clinical trial averages represent the mean of a large and diverse population. Individual results vary substantially based on:

• Dose reached: Many patients cannot tolerate the maximum dose due to gastrointestinal side effects. Lower doses produce proportionally less weight loss (approximately 8–12% for semaglutide 1 mg; 14–17% for tirzepatide 10 mg).
• Dietary adherence: GLP-1s suppress appetite but do not eliminate caloric consumption. Concurrent dietary changes significantly amplify results.
• Physical activity: Exercise preserves lean muscle mass during weight loss, improving body composition outcomes.
• Baseline metabolic health: Individuals with insulin resistance, PCOS, or metabolic syndrome may respond differently than those without.
• Genetic variability: Emerging pharmacogenomic research suggests that GLP-1 receptor gene variants affect medication response.

Weight maintenance after stopping GLP-1 medications

A critical finding from extension studies (including the STEP 4 trial) is that most patients regain a significant portion of lost weight after discontinuing GLP-1 therapy. In STEP 4, patients who stopped semaglutide regained approximately two-thirds of their lost weight within one year.

This reflects the chronic nature of obesity as a metabolic condition — not a failure of willpower or medication. Most clinical guidelines now classify GLP-1 therapy for obesity as a long-term or indefinite treatment, similar to antihypertensive or cholesterol-lowering medications.