Orforglipron is a copy of the gut hormone GLP-1. Tesofensine is a small molecule rather than a peptide.
GLP-1 is what your gut releases after a meal to tell your brain you have eaten.
They are aimed at different things: Orforglipron at weight loss (oral); Tesofensine at weight loss.
| Comparison | Orforglipron Foundayo · LY3502970 | Tesofensine NS2330 |
|---|---|---|
| How it works | How it works Orforglipron reaches the same receptor as semaglutide by a completely different chemical route. It is not a peptide at all, which is precisely why it can be a pill. | How it works Tesofensine is a stimulant-class small molecule, not a peptide. It was originally developed for Parkinson's disease, and the weight loss was noticed as a side effect. |
| What it is | The first GLP-1 weight-loss pill, approved in 2026 and taken any time of day. | An experimental appetite-suppressing pill with strong weight-loss numbers. |
| Status | FDA approvedFDA-approved | In trialsInvestigational |
| Typical dose | 0.8–17.2 mg per day | 0.25–0.5 mg per day |
| How often | Daily | Daily |
| Stays active | ~2-3 days | Not established |
| Dose comes from | FDA drug label | Published human study |
| Cycled? | Not cycled in the trials Clinical trial protocol | Continuous daily dosing, studied to 24 weeks Published human study |
| What it does | ||
| Drug class | Oral GLP-1 (small molecule) | Triple reuptake inhibitor (not a peptide) |
| Used for | People use it for weight loss without injections. In trials people lost roughly 12 to 15% of their body weight. | An experimental appetite-suppressing pill with strong weight-loss numbers. |
| Receptors hit | GLP-1 | — |
| Numbers | ||
| Full dose line | 0.8 up to 17.2 mg per day (six steps, 30 days apart) | 0.25 up to 0.5 mg per day |
| Why that cycle | Given continuously for the whole study period: ATTAIN-1, 72 weeks. The dose is stepped up at the start, which is a ramp rather than a cycle, and no trial in this class built in a planned break. | Given daily without breaks in the trials. The phase 2 study ran 24 weeks at up to 1 mg daily, with an extension to 48 weeks. No cycling was used or tested. |
| Weight / effect | Not measured in a trial | Not measured in a trial |
| Chain length | Not disclosed | Not disclosed |
| Common vial | — | — |
| Before you start | ||
| Route | By mouth (oral) | By mouth (oral) |
| Do not use if | A personal or family history of medullary thyroid cancer, or the genetic condition MEN 2, which is a boxed warning Taking another GLP-1 medicine at the same time Pregnancy Children, where it has not been established | Uncontrolled high blood pressure Heart rhythm problems A history of psychiatric conditions Pregnancy |
What separates them
Proof behind the dose. Orforglipron has a dose taken straight off an FDA drug label. Tesofensine has a dose from a published human study.
What doesn't differ: They are both taken the same way (by mouth) and on the same schedule (daily). Neither has a measured effect size from a published trial, so there is no number to rank them on.
What people actually report
Orforglipron
- Stomach side effects like nausea.
- It is not approved, and it is a pill rather than a peptide.
- A lump or swelling in your neck, hoarseness, or trouble swallowing
- Severe stomach pain that spreads to your back
Tesofensine
- It acts like a stimulant and can raise heart rate and blood pressure, so it carries more heart-related risk than other options.
- It is not approved, and not a peptide.
- A racing or pounding heartbeat
- Severe agitation, panic, or a marked change in mood
Side effects are what users and trials report most often, not a complete list. Anything sudden, spreading, or breathing-related is an emergency regardless of which compound caused it.
People also compare
This comparison does not cover cost, long-term safety, or how you personally will respond. Effect figures come from separate trials in different populations and are not always directly comparable to each other. Nothing here is medical advice or a recommendation to use any of these. Talk to a clinician about your own situation.