Methodology · Index v1.0
GLP-1 Performance Index: how it works
One question: how much weight does a drug take off for each unit of side effects it causes? Here is every step, so you can check our work or disagree with it.
The formula
Computed from the top dose of each drug's main Phase 3 obesity trial
Each percentage point of people quitting adds one point to the burden (w = 1). That already weighs heavily: the stomach score is an average of four symptoms, so one quitter counts as much as four people each having one symptom. Most people who quit also had stomach side effects, which are already counted, so a higher weight would count them twice.
Who qualifies
- A completed Phase 3 obesity trial. Phase 2 results are too small and short to rank fairly.
- At least 3 of 4 stomach side-effect rates plus the quit rate must be published.
- A 10% efficacy floor, so a very gentle but weak drug cannot top the table.
Try a different weighting
Move the slider to change how much quitting counts. The ranking updates live.
* Small trial with dose reductions. See the note under Worked numbers.
Sensitivity check
Ranking order under four weightings. Tirzepatide leads at every setting we tested.
| Rank | w = 0 | w = 1 (default) | w = 2 | w = 3 |
|---|---|---|---|---|
| 1 | Tirzepatide | Tirzepatide | Tirzepatide | Tirzepatide |
| 2 | Retatrutide | Retatrutide | Retatrutide | Retatrutide |
| 3 | CagriSema | CagriSema | CagriSema | CagriSema |
| 4 | Oral semaglutide 25 mg* | Oral semaglutide 25 mg* | Oral semaglutide 25 mg* | Oral semaglutide 25 mg* |
| 5 | Semaglutide 2.4 mg | Semaglutide 2.4 mg | Semaglutide 2.4 mg | Semaglutide 2.4 mg |
| 6 | Orforglipron | Orforglipron | Orforglipron | Orforglipron |
Worked numbers
| Drug | Weight loss | Nausea | Vomiting | Diarrhea | Constip. | Quit | Stomach | Burden | Index | Status |
|---|---|---|---|---|---|---|---|---|---|---|
| TirzepatideSURMOUNT-1 | 22.5% | 31.0% | 12.2% | 23.0% | 11.7% | 6.2% | 19.5 | 25.7 | 8.76 | Ranked |
| RetatrutideTRIUMPH-1 | 28.3% | 42.4% | 25.3% | 32.0% | 26.1% | 11.3% | 31.5 | 42.8 | 6.62 | Ranked |
| CagriSemaREDEFINE 1 | 22.7% | 55.0% | 26.1% | n/r | 30.7% | 6.0% | 37.3 | 43.3 | 5.25 | Ranked |
| Oral semaglutide 25 mg*OASIS 4 | 16.6% | 46.6% | 30.9% | 17.6% | 20.1% | 6.9% | 28.8 | 35.7 | 4.65 | Ranked |
| Semaglutide 2.4 mgSTEP 1 | 16.9% | 44.2% | 24.8% | 31.5% | 23.4% | 7.0% | 31.0 | 38.0 | 4.45 | Ranked |
| OrforglipronATTAIN-1 | 12.4% | 33.7% | 24.0% | 23.1% | 25.4% | 10.3% | 26.6 | 36.9 | 3.36 | Ranked |
* Wegovy pill: small trial with dose reductions. OASIS 4 included 307 adults, only about 205 of them on the pill, against 1,961 in STEP 1 for the injection, so its side-effect rates are less reliable. In addition, 18.6% of participants who completed treatment ended on a lower dose than 25 mg, which probably kept some from stopping and lowered the reported 6.9% discontinuation rate. Its ranking against the injection should be treated as provisional.
Limitations we want you to know
- Separate trials. No trial tested all these drugs together. Lengths (64 to 80 weeks), populations and dose schedules differ.
- Raw rates, not placebo-adjusted. Some people on placebo also report nausea. Placebo figures are not published for every trial, so we use raw rates for everyone to stay consistent.
- Estimands. Weight loss uses the efficacy (on-treatment) estimand where reported.
- Trial size varies. Rates from small trials are less precise. Drugs whose main trial had fewer than 500 participants are marked with an asterisk (*), and the note explains any other limits of that trial, such as dose reductions.
- Severity is not captured. A mild and a severe episode of nausea count the same.
- Not medical advice. The best drug for a person depends on their health, other medicines and cost.
Data conventions
Data as of Oct 10, 2026. Each figure links to its source on the compound page. Spotted an error? Corrections are logged in the changelog.