Tirzepatide and Retatrutide: What the Trials Found

Two compounds, three hormones

Both of these copy hormones your gut releases after eating. Those hormones tell the brain you have had enough and tell the pancreas to handle glucose. The compounds are longer-lasting versions of the same signals.

The difference between them is how many of those signals they carry.

Tirzepatide works on two receptors: GLP-1 and GIP, both gut hormones involved in appetite and blood sugar. Retatrutide works on three — the same two, plus glucagon, a hormone that increases the rate at which the body burns energy.

That third receptor is the whole argument for retatrutide. In theory, the first two reduce how much is eaten while the third increases how much is spent.

What the tirzepatide trial found

The main study is SURMOUNT-1, published in the *New England Journal of Medicine* in 2022.

Participants started at an average body weight of 104.8 kg, with an average BMI of 38. After 72 weeks, average weight change was:

• −15.0% on 5 mg weekly
• −19.5% on 10 mg weekly
• −20.9% on 15 mg weekly
• −3.1% on placebo

At the top dose that is roughly 22 kg from a 105 kg starting point. Between 85% and 91% of participants lost at least 5% of their body weight, against 35% on placebo.

Those are unusually large numbers for a drug trial. They are also from a 72-week study in people with obesity, run with medical supervision — not a fitness intervention in healthy adults.

What the retatrutide trial found

Retatrutide is earlier in development. The phase 2 trial, published in the same journal in 2023, enrolled 338 adults and ran for 48 weeks.

Average weight change at 48 weeks:

• −8.7% on 1 mg
• −17.1% on 4 mg
• −22.8% on 8 mg
• −24.2% on 12 mg
• −2.1% on placebo

At 48 weeks, 92% of participants had lost at least 5% of body weight, 75% had lost at least 10%, and 60% had lost at least 15%.

Read the timeframes before comparing the two sets of numbers. Retatrutide reached −24.2% in 48 weeks; tirzepatide reached −20.9% in 72. That looks favourable for retatrutide, but a phase 2 trial with 338 people is not the same evidence as a phase 3 trial with thousands, and later trials frequently produce smaller effects than earlier ones.

What the trials do not tell you

Retatrutide is not approved anywhere. It has not completed phase 3. Tirzepatide is an approved medicine in many countries, prescribed and monitored by doctors — which is a different situation entirely from a research compound.

Some of the loss is not fat. Rapid weight loss of this size takes lean tissue with it. The trials measured total body weight; body composition substudies are still emerging. This is the single most common reason people research growth hormone secretagogues such as CJC-1295 + Ipamorelin alongside them.

Side effects were mostly digestive, and mostly during dose escalation — nausea, diarrhoea, constipation, vomiting. They were the main reason participants dropped out.

Weight returns when the compound stops. Follow-up work on this drug class consistently shows regain after discontinuation. These trials measured what happens during treatment, not after it.

Where they sit alongside other research

Both are studied in combination with compounds addressing what the appetite signal alone does not: MOTS-c for glucose handling and mitochondrial function, and growth hormone secretagogues for lean tissue. The Body Recomposition protocol is built around exactly that combination.

Everything described here is supplied for laboratory research only. It is not medical advice, and it is not for human or veterinary use.