Eloralintide vs Retatrutide: Amylin or Three Incretin Receptors

Eloralintide and retatrutide are both investigational once-weekly injections from Eli Lilly for obesity, but they act on different hormone systems. Eloralintide is a selective amylin receptor agonist. Retatrutide activates three receptors from the incretin and glucagon family: GIP, GLP-1 and glucagon. Neither is approved anywhere, and no trial has compared them.

They are less rivals than two separate bets on how to reduce food intake. Eloralintide copies a pancreatic hormone, amylin, that is released alongside insulin; retatrutide extends the GLP-1 approach that semaglutide and tirzepatide made familiar.

What each one is

• Eloralintide (LY3841136) is a long-acting amylin analogue. In cell assays it preferentially activated the human amylin 1 receptor, about 12-fold over the calcitonin receptor and 11-fold over the amylin 3 receptor, and its pharmacokinetics support once-weekly dosing (Briere 2025). Peptide Library has no profile for it yet; this article cites its trials directly.

• Retatrutide (LY3437943) is a single peptide that is an agonist at the GIP, GLP-1 and glucagon receptors, given once weekly (Jastreboff 2023). See the retatrutide profile or the plain-language introduction.

The closest approved relatives make the split clearer. Pramlintide is an older, short-acting amylin analogue; tirzepatide is a GIP and GLP-1 agonist, and retatrutide adds glucagon to it. The eloralintide vs cagrilintide comparison covers how eloralintide differs from the other long-acting amylin analogue.

What the published trials measured

The two programmes are at different points and have studied different groups, so each is described on its own. We have deliberately not copied weight-loss percentages from the two programmes into this article: placed side by side, figures from trials with different populations, lengths and analysis methods invite exactly the cross-trial ranking the evidence cannot support. Each paper reports its own results against its own placebo group.

Eloralintide

• Single doses, phase 1. 48 healthy participants received single doses from 0.04 to 12 mg or placebo. Body weight fell after single 4 mg and 12 mg doses compared with placebo over four weeks, and most adverse events were mild (Briere 2025).

• Repeated doses, phase 1. 100 participants with obesity or overweight received once-weekly eloralintide or placebo for 12 weeks in five ascending-dose cohorts, without dose escalation. The most common adverse events were decreased appetite (19%), headache (12%) and fatigue (11%); diarrhoea (10%), nausea (8%) and vomiting (4%) were less frequent (Bhattachar 2026).

• Phase 2. 263 adults with obesity, or overweight with a weight-related condition and without type 2 diabetes, were randomised to placebo or eloralintide 1, 3, 6 or 9 mg once weekly, or to two escalation schemes (6 then 9 mg, or 3 then 9 mg), for 48 weeks. Weight fell in a dose-dependent way compared with placebo. The most common adverse events were nausea and fatigue, with rates that varied by dose arm (Billings 2025).

• Phase 3. Lilly has registered several phase 3 trials, including NCT07321886 (about 1,980 adults with obesity or overweight without type 2 diabetes, four eloralintide doses against placebo, weight change at week 64). None has reported results.

Retatrutide

• Phase 2. 338 adults with obesity, or overweight with a weight-related condition, received 1, 4, 8 or 12 mg once weekly or placebo for 48 weeks, with lower starting doses in some arms. The most common adverse events were gastrointestinal, dose-related and partly reduced by a lower starting dose; heart rate rose in a dose-dependent way, peaking at 24 weeks (Jastreboff 2023).

• TRIUMPH-1, phase 3. 2,339 adults with obesity without diabetes received 4, 9 or 12 mg once weekly or placebo for 80 weeks, including subgroups with knee osteoarthritis and obstructive sleep apnoea. Body weight fell compared with placebo at every dose, and pain and sleep apnoea measures improved in the subgroups; gastrointestinal events were the most common adverse events (Jastreboff 2026).

• TRIUMPH-2, phase 3. 1,152 adults with obesity and type 2 diabetes received 4, 9 or 12 mg or placebo for 80 weeks. Diarrhoea and nausea were more common than with placebo, as were hypotension and dysaesthesia (Bellido 2026).

• TRANSCEND-T2D-1, phase 3. 537 adults with type 2 diabetes managed by diet and exercise received 4, 9 or 12 mg or placebo for 40 weeks, with HbA1c as the primary outcome (Bajaj 2026).

The retatrutide dosage chart sets out each arm against its source, and the retatrutide side effects guide covers the adverse-event reporting.

Where they differ beyond the mechanism

• Tolerability profile. Retatrutide's adverse events are dominated by gastrointestinal effects, as with other GLP-1-based drugs. In eloralintide's trials, fatigue and decreased appetite feature alongside nausea, and gastrointestinal events were infrequent in the 12-week phase 1 study. Different trial designs make these rates impossible to line up directly.

• Heart rate. Retatrutide raised heart rate in a dose-dependent way in phase 2. A 2026 review of eloralintide's early studies reported reductions in pulse rate, in contrast with GLP-1 receptor agonists, while noting that the evidence comes from small, short phase 1 and 2 studies (Sigalov 2026).

• How far along the evidence is. Retatrutide has published phase 3 results in thousands of participants. Eloralintide's published human data come from fewer than 500 participants across three studies.

• Combination plans. Lilly is testing eloralintide with tirzepatide as a combination called EloraTZP, in a phase 3 trial that compares it with each drug alone and with placebo over 100 weeks (NCT07881432). We found no registered trial combining eloralintide with retatrutide (ClinicalTrials.gov search, November 2026).

What the evidence does not show

• Which one causes more weight loss. No trial has randomised people to eloralintide versus retatrutide. Any percentage comparing them is arithmetic across separate trials with different populations, durations and analysis methods.

• Long-term safety of eloralintide. Its longest published trial lasted 48 weeks.

• Cardiovascular outcomes. Neither drug has reported a cardiovascular outcomes trial.

Frequently asked questions

Is eloralintide a GLP-1 drug?

No. It is an amylin receptor agonist. Amylin is a different hormone, released by the pancreas alongside insulin.

Is eloralintide stronger than retatrutide?

There is no way to say from the evidence. No trial has compared them, and their trials differ in population, length and design.

Are eloralintide and retatrutide approved?

No. Both are investigational drugs in Lilly's clinical programme. Retatrutide has published phase 3 results; eloralintide's phase 3 trials are registered but have not reported.

Can eloralintide and retatrutide be combined?

No published or registered trial has tested them together. Lilly's registered combination for eloralintide is with tirzepatide (EloraTZP).