Eloralintide vs Retatrutide: Trials, Doses, Side Effects

Eloralintide, an amylin agonist in Phase 3, against retatrutide, a triple agonist nearing an FDA filing: how their trials, doses and side effects compare.

Retatrutide has the bigger numbers and far more evidence behind them. Eloralintide works through a different hormone and runs two to three years behind on trial timelines. In their 48-week Phase 2 trials, the top doses tested produced mean weight loss of 24.2% with retatrutide 12 mg and 20.1% with eloralintide 9 mg, both under an efficacy estimand. Retatrutide has since reported 25.0% at 80 weeks in Phase 3, counting everyone randomized. No trial has tested the two against each other. Neither drug is approved anywhere, and the doses named here are the ones trials tested, not recommendations.

Eloralintide vs retatrutide at a glance

How the two drugs work

Amylin is a hormone the pancreas releases along with insulin. It slows stomach emptying, holds back glucagon and helps end meals through signals in the brain, per a 2026 review. The eloralintide peptide copies that signal, and in cell assays it activated the human AMY1 receptor 12-fold more potently than the calcitonin receptor.

That selectivity is the pitch. Cagrilintide, the amylin half of Novo Nordisk's CagriSema, activates amylin and calcitonin receptors with similar potency. Lilly's researchers think selectivity, the long half-life or both may explain better tolerability than other amylin drugs, though they call that evidence indirect. Our eloralintide vs cagrilintide page tests the claim, and amylin analogs compared covers the class.

Retatrutide, often shortened to reta, is one peptide that switches on three receptors: GLP-1 and GIP, the pair tirzepatide targets, plus glucagon. GLP-1 and GIP are gut hormones that raise insulin after meals, and GLP-1 also curbs appetite. Glucagon tells the liver to release stored fuel. See retatrutide vs tirzepatide for what the third receptor adds, and our UBT251 guide for another triple agonist.

Weight loss: the best numbers and their fine print

Start with the 28.3%. It led Lilly's release, and it overstates what the average participant got. The efficacy estimand describes the result had everyone stayed on the drug. The NEJM paper's main analysis counts everyone randomized, whatever happened next, and lands at 25.0%. Both are honest; the second is closer to real life, where some people stop.

The fairest pairing here is Phase 2 against Phase 2: both 48 weeks, both efficacy estimands, and similar starting weights of 109.1 kg and 107.7 kg. Subtract each trial's placebo result from 24.2% and 20.1% and the gap shrinks from 4.1 points to 2.4 (22.1 against 19.7). That is arithmetic across two trials, not a head-to-head result.

In type 2 diabetes, eloralintide looks weaker. In the EloraTZP trial, eloralintide alone reached 8.2% to 12.3% at 48 weeks against 3.0% on placebo, on the efficacy estimand. Retatrutide reached 11.5% to 15.3% across 4 to 12 mg, against 2.6%, in TRANSCEND-T2D-1 even though that trial ran only 40 weeks and used the stricter treatment-regimen estimand. Estimands, lengths and populations all differ, so no precise gap holds.

The trials behind the numbers

The trials enrolled different people. Women made up 78% of the eloralintide trial and 48% of the retatrutide trial, mean BMI was 39.1 against 37.3, and placebo lost 0.4% in one trial and 2.1% in the other.

The evidence is lopsided too. Retatrutide's four core Phase 3 trials enrolled more than 5,800 people. Eloralintide's main monotherapy trial had 263 people, only 54 of them on 9 mg.

And we don't know eloralintide's top dose. Its main Phase 3 trials list doses only as "Dose 1" to "Dose 4", so 9 mg may not be the ceiling.

Side effects: different drugs, different problems

The two columns come from separate trials. The dropout row counts people who left the study, not those who stopped the drug and stayed in follow-up, so it understates treatment stops.

Fatigue is the surprise. In the phase 2 results posted on ClinicalTrials.gov, it affected 43% of people on eloralintide 9 mg and 46% on the 6-then-9 mg schedule, against 11% on placebo, while retatrutide's 12 mg arm sat at 10%. The Phase 1 study also logged mood-related events in four people. Three of the four were on 12 mg; all three stopped treatment and recovered within 2 to 4 days. Phase 3 should show whether that was noise.

Nausea did not climb neatly with eloralintide's dose: 64% on the fixed 6 mg arm, 33% on the fixed 9 mg arm. Lilly says slower escalation lowered these events. Retatrutide's Phase 2 shows how much the first dose matters: reaching 8 mg from a 4 mg start brought nausea in 21 of 35 people, against 6 of 35 from a 2 mg start.

In Phase 3, 12.5% of TRIUMPH-1 participants on 12 mg reported dysesthesia, an unpleasant skin sensation, against 0.9% on placebo, and 11.3% stopped for adverse events against 4.9%. In TRIUMPH-4, 18.2% on 12 mg stopped treatment because of adverse events, against 4.0% on placebo. Lilly said those stops were highly correlated with starting BMI and included people who felt they had lost too much weight.

Heart rate moves in opposite directions

Retatrutide raised heart rate in Phase 2 in a dose-dependent way that peaked at 24 weeks and then eased, by up to 6.7 beats per minute. In eloralintide's Phase 1, pulse fell 14.4 beats per minute on 12 mg after 12 weeks, against 3.4 on placebo, with no symptomatic bradycardia. In Phase 2, bradycardia was logged as an adverse event in 3 of 54 people on 9 mg and none on placebo, in a trial that had excluded people with a history of it. Whether a slower pulse helps or harms needs larger trials.

Doses tested and trial schedules

Both were injected under the skin once a week. Eloralintide's half-life of about 14 days keeps blood levels relatively flat across the week, with peak-to-trough ratios of 1.28 to 1.38 in Phase 1. Retatrutide's is about 6 days.

Eloralintide's Phase 2 used fixed doses of 1, 3, 6 or 9 mg, plus two step-ups: 6 mg for 20 weeks then 9 mg, and 3 mg, then 6 mg, then 9 mg from week 9 (registry). Retatrutide's Phase 2 tested 1, 4, 8 and 12 mg, with 2 mg or 4 mg starting doses (NEJM). In TRIUMPH-1, everyone started at 2 mg and stepped up every four weeks to 4, 9 or 12 mg (Lilly).

These are trial doses, nothing more. Our eloralintide and retatrutide pages have the background on each drug.

Where each drug stands in October 2026

One wrinkle for retatrutide: the FDA has decided it is neither a protein nor a biological product, so it would need a standard drug application. Lilly is contesting that in court and still plans a biologics filing. BioSpace reported that a rejected one could delay the drug.

Eloralintide's dates are simpler: all five ENLIGHTEN trials measure weight at week 64, with primary completion between January and June 2028. Our estimate, not Lilly's: a filing in 2028 at the earliest, so approval before 2029 would be a surprise. More detail is in our Phase 2 write-up.

Eloralintide as a partner drug

Lilly's trial list suggests eloralintide's future is as a partner as much as a rival. ENLIGHTEN-6 adds it to stable incretin therapy in people who still have obesity. The EloraTZP trial paired it with tirzepatide in 367 adults with type 2 diabetes, and eloralintide 9 mg with tirzepatide 15 mg produced 23.3% weight loss against 14.8% on tirzepatide 15 mg alone at 48 weeks, on the efficacy estimand. Tolerability looked like the price: 10.8% to 27.0% of people on the combinations stopped treatment because of adverse events, against 0% to 10.8% on eloralintide alone, 2.9% on tirzepatide and, oddly, 16.7% on placebo, a reminder of how noisy small arms are.

Phase 3 trials of the pair, AMPLIFY-2 and AMPLIFY-1, are due to start in November and December 2026, with primary completion in October 2029. Our EloraTZP breakdown goes arm by arm.

ClinicalTrials.gov lists no trial of eloralintide with retatrutide. If the question is whether amylin can beat a triple agonist, eloralintide alone is probably the wrong contender. EloraTZP is the fairer test.

Sources

• Eloralintide: Lancet Phase 2, registry results, discovery paper, Phase 1 study
• Retatrutide: NEJM Phase 2, registry results, TRIUMPH-1, TRIUMPH-2 and TRANSCEND-T2D-1
• Lilly announcements: eloralintide Phase 2, TRIUMPH-4, TRIUMPH-1, TRIUMPH-2 and 3 and EloraTZP
• BioSpace on the FDA classification dispute

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