Retatrutide and Orforglipron: A Triple-Agonist Injection and a GLP-1 Pill
Retatrutide and orforglipron are among the newer compounds drawing the most attention in weight and metabolic research. Eli Lilly developed both. Otherwise they have little in common. Retatrutide is injected once a week and acts on three receptors. Orforglipron is swallowed once a day and acts on one.
They have not yet been tested against each other in a trial. This page therefore places each compound's own trial results next to the other's and describes how the two differ. The content is educational and based on published studies. Research compounds from NordPeps are sold strictly for laboratory work.
On this page
Summary table
| Retatrutide | Orforglipron | |
|---|---|---|
| Brand name | None so far (investigational) | Foundayo |
| Molecule type | Peptide | Small molecule, not a peptide |
| Receptor targets | GLP-1 + GIP + glucagon (triple) | GLP-1 (single) |
| Form used in trials | Injection, once a week | Tablet, once a day, no food or water rules |
| Pivotal obesity trial (highest dose) | TRIUMPH-1: −28.3% after 80 weeks | ATTAIN-1: −12.4% after 72 weeks |
| Discontinued due to adverse events (highest dose vs placebo) | 11.3% vs 4.9% | 10.3% vs 2.7% |
| Regulatory status (October 2026) | Investigational; no approval in the US or EU | US approval April 2026, UK approval August 2026; EU review by the EMA ongoing |
Three receptors against one
Orforglipron works as a single agonist. It engages the GLP-1 receptor and nothing else, which is also semaglutide's target.
Retatrutide works as a triple agonist, with GLP-1, GIP and glucagon receptors as its targets. The glucagon target is what it adds. Research associates it with energy expenditure and with fat metabolism in the liver. It is the principal reason retatrutide is seen as going beyond dual agonists like tirzepatide.
Tablet against injection
Nearly all GLP-1 compounds are peptides. Being amino-acid chains, they would be broken down in the digestive tract, so they are injected. Retatrutide belongs to this group, and its trials used a weekly injection.
Orforglipron breaks the pattern. As a small molecule rather than a peptide, it is not destroyed by digestion and can be given as a daily tablet. According to Lilly, it can be taken at any hour, without restrictions on food or water. Oral semaglutide (Rybelsus) is different again: it is a peptide in tablet form and must be taken on an empty stomach.
Results from each compound's trials
- Retatrutide, TRIUMPH-1 (2026): enrolled 2,339 adults without diabetes who had obesity, or overweight with a weight-related condition. On the highest dose, mean body weight dropped 28.3% over 80 weeks, against 2.2% with placebo.
- Orforglipron, ATTAIN-1 (2025): enrolled 3,127 adults with obesity and no diabetes. On the highest dose, mean body weight dropped 12.4% over 72 weeks, against 0.9% with placebo. The New England Journal of Medicine published the trial.
Both numbers were calculated the same way, using the efficacy estimand. Still, they come from two different trials with different participants and durations. They are not a head-to-head result.
Tolerability and discontinuation
The two compounds show the side-effect profile typical of the GLP-1 class, mainly gastrointestinal: nausea, diarrhoea, constipation and vomiting. At the highest dose, the proportion of trial participants who discontinued because of adverse events was:
- Retatrutide (12 mg): 11.3%, against 4.9% with placebo.
- Orforglipron (36 mg): 10.3%, against 2.7% with placebo.
Regulatory position in 2026
Orforglipron received US FDA approval on 1 April 2026 as Foundayo. The approval covers adults with obesity, or with overweight and weight-related conditions. On 10 August 2026 the UK regulator, the MHRA, authorised it for weight management and for type 2 diabetes. In the EU, the European Medicines Agency's expert committee (CHMP) recommended approval on 15 October 2026; the European Commission's decision is pending.
Retatrutide remains investigational, with no approval in the US or the EU. Lilly reported a number of Phase 3 TRIUMPH results during 2026.
Foundayo is an Eli Lilly trademark. NordPeps is not a pharmacy and has no affiliation with Eli Lilly. Its research-grade material is intended for in vitro and laboratory work alone, never for use in humans or animals.
Available from NordPeps
NordPeps offers retatrutide in 10 mg research vials for €84.95. Certificates from an independent third-party laboratory are published per batch on /certificates as they become available. Orforglipron is not stocked. Sold for laboratory research only.
Sources
- Eli Lilly: TRIUMPH-1 topline results for retatrutide, 21 May 2026
- Wharton S et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment (ATTAIN-1). N Engl J Med 2025
- Eli Lilly: ATTAIN-1 topline results for orforglipron, 16 September 2025
- Eli Lilly: FDA approval of Foundayo (orforglipron), 1 April 2026
- UK MHRA: orforglipron authorised for weight management and type 2 diabetes, 10 August 2026
- European Medicines Agency: new oral GLP-1 medicine for weight management and type 2 diabetes (CHMP opinion on Foundayo), 16 October 2026
Frequently asked questions
Does retatrutide show a larger effect than orforglipron?
They have never been compared in the same trial. In each compound's own pivotal trial, at the highest dose, mean weight fell by about 28% after 80 weeks with retatrutide and about 12% after 72 weeks with orforglipron.
What is Foundayo?
It is the brand name for orforglipron, Eli Lilly's once-a-day GLP-1 tablet. The US FDA granted approval on 1 April 2026.
Does orforglipron have European approval?
Not yet. On 15 October 2026 the EMA's expert committee (CHMP) recommended EU approval of Foundayo (orforglipron); the European Commission's decision is pending. The UK authorised it in August 2026.
Has retatrutide been approved?
No. It is still investigational and has no approval from US or EU regulators.