Research Library

RT vs TZ: What the Trial Data Shows

RT adds glucagon receptor agonism to the GIP/GLP-1 dual mechanism of TZ.

Summary

RT adds glucagon receptor agonism to the GIP/GLP-1 dual mechanism of TZ.

Last reviewed 2026-09-01

What it is

A comparison of two multi-receptor incretin agonists: TZ, a GIP/GLP-1 dual agonist with completed phase 3 programmes, and RT, an investigational GIP/GLP-1/glucagon triple agonist.

TZ's phase 3 programmes reported from 2021. RT phase 2 obesity results were published in 2023; phase 3 trials are ongoing.

Both are synthetic multi-agonist peptides developed from incretin pharmacology.

The comparison tests whether adding a third receptor — glucagon, which raises energy expenditure — produces additive benefit or additive burden.

How it works

In plain terms

Both mimic gut hormones that reduce appetite and slow stomach emptying. RT adds a third signal that increases how much energy the body burns, rather than only reducing how much is eaten.

Technical detail

TZ is a GIP receptor and GLP-1 receptor dual agonist, biased toward GIP receptor affinity. RT adds glucagon receptor agonism. The balance between the three activities is the central design problem.

Pathways involved

GLP-1R: satiety, delayed gastric emptying, glucose-dependent insulin release
GIPR: insulin secretion and adipose tissue effects
GCGR (RT only): hepatic lipolysis and energy expenditure

Current research

Laboratory research

Receptor selectivity and potency profiles are published for both molecules.

Animal research

Outcome details are reported in the cited peer-reviewed literature.

Human research

RT's phase 2 obesity trial reported approximately 24.2% at 48 weeks on the highest dose. These figures come from different trial phases, populations, durations and titration schedules, so the difference cannot be treated as a measured head-to-head result. Gastrointestinal adverse events were dose-related in both; RT phase 2 also reported dose-dependent heart rate increases.

Ongoing research

The Phase 3 trials for RT are the first data that will support firmer conclusions.

What is being investigated

Whether glucagon receptor addition improves weight outcomes beyond dual agonism
Energy expenditure contribution versus appetite suppression
Heart rate and hepatic glucose effects of triple agonism
Tolerability at matched titration schedules

These are research directions reported in the literature, not established effects or recommendations.

Risks, limitations and unknowns

Read this section before the rest

Cross-trial comparison of phase 2 and phase 3 results is not valid evidence of superiority
RT has no completed phase 3 safety data and is not approved anywhere
Glucagon receptor agonism raises hepatic glucose output and has shown dose-dependent heart rate increases
Gastrointestinal adverse events are common with both mechanisms
Outcome details are reported in the cited peer-reviewed literature.

Evidence ratings

TZ human data

Strong

Completed phase 3 programmes with large populations.

RT human data

Preliminary

Phase 2 only; phase 3 ongoing.

Head-to-head comparison

None

No direct comparative trial has been conducted.

Comparisons

TZ vs SM

The one comparison with direct trial data.

Cagrilintide vs SM

A different mechanism class.

References

[1]RT phase 2 obesity trial — PubMed / NEJM, 2023
[2]The pivotal 72-week obesity trial TZ obesity trial — PubMed / NEJM, 2022
[3]The RT phase 3 programme — ClinicalTrials.gov, ongoing
Reference links open searches and records on PubMed and ClinicalTrials.gov so that every statement above can be traced to primary literature.

Frequently asked questions

Is RT stronger than TZ?+

Phase 2 RT figures are numerically larger, but no head-to-head trial exists and phase 2 results are not comparable to phase 3 results.

What is the mechanistic difference?+

TZ targets GIP and GLP-1 receptors; RT adds glucagon receptor agonism, which raises energy expenditure.

Is RT approved?+

No. It remains investigational, with phase 3 trials ongoing.

Do both cause gastrointestinal side effects?+

Yes. Nausea, vomiting, diarrhoea and constipation are dose-related and common across incretin agonists.

When will a fair comparison be possible?+

Only after RT phase 3 results are published, and strictly speaking only with a direct head-to-head trial.

Continue your research

RT research

TZ research

Incretin mechanisms