Comparison

Retatrutide vs Tirzepatide

Reviewed 22 October 2026 · How we research

Retatrutide is often described as “the next Mounjaro”. Both come from Eli Lilly and share the GIP and GLP-1 actions; retatrutide adds glucagon-receptor activity. No head-to-head trial has been published, so comparisons rely on separate trials.

Retatrutide vs Tirzepatide at a glance

How they work

Retatrutide

Each receptor contributes something different. GLP-1 activation slows gastric emptying and reduces appetite through the brainstem and hypothalamus. GIP activation appears to enhance the GLP-1 effect on appetite and improves insulin response. Glucagon receptor activation is the new ingredient: it raises energy expenditure and promotes fat oxidation in the liver — which is why liver-fat reduction was one of the striking findings in the phase 2 sub-study.

The molecule carries a fatty-acid side chain that binds albumin in the blood, slowing clearance and giving the roughly six-day half-life that allows weekly dosing in trials.

Tirzepatide

GLP-1 receptor activation slows stomach emptying and signals fullness to the brain. GIP receptor activation was once expected to work against weight loss, but tirzepatide showed the combination produces more appetite suppression and better insulin sensitivity than GLP-1 activation alone. The peptide is built on the GIP sequence and modified with a C20 fatty-diacid chain that binds albumin, giving the five-day half-life.

Side effects compared

Retatrutide

The side-effect pattern in trials looked like other incretin drugs, mostly gastrointestinal and mostly during dose increases:

• Nausea, diarrhoea, vomiting and constipation — the most common, and dose-related.
• Higher resting heart rate, peaking around week 24 and easing later.
• Reduced appetite (the intended effect) and occasional fatigue.
• Skin sensations (dysaesthesia) were noted on higher doses in phase 3 reporting.

Starting at a lower dose and stepping up reduced GI events in the phase 2 trial — the 4 mg and 8 mg arms that began at 2 mg had fewer events than those that started higher. Long-term safety data will only come from the phase 3 programme.

Tirzepatide

• Gastrointestinal: nausea, diarrhoea, constipation, vomiting and indigestion — most common in the first weeks after each dose increase.
• Reduced appetite, burping, abdominal pain, fatigue.
• Less common but serious: gallbladder problems, pancreatitis, severe dehydration from vomiting/diarrhoea.
• The MHRA has warned that Mounjaro may reduce the effectiveness of oral contraceptives in people who are overweight, particularly after starting and after each dose increase.

Carries the class warning about thyroid C-cell tumours seen in rodents; it is not used in people with a personal or family history of medullary thyroid cancer.

Bottom line

Cross-trial numbers favour retatrutide, but different populations and durations make direct comparison unreliable. Tirzepatide is a licensed, prescribable medicine; retatrutide is not available outside trials.