Retatrutide Research: Trials, Data & What the Studies Show

The landmark phase 2 obesity trial

The first major trial to test whether triple hormone receptor agonism produces a meaningfully larger effect than existing single- and dual-agonist approaches.

338 adults with obesity or overweight · 48 weeks · randomised, double-blind, placebo-controlled

24.2%

Mean weight reduction (12 mg)

at 48 weeks

86%

Mean reduction in liver fat

93%

MASLD resolution (highest dose)

of patients with baseline steatosis

• Weight reduction was dose-dependent and greater than placebo at every dose tested.
• Meaningful reduction appeared within the first 12 weeks and continued to accumulate across the full 48-week period, with no clear plateau by study end.
• Alongside weight change, the trial reported reductions in systolic blood pressure and improvements in lipid parameters including LDL cholesterol and triglycerides.
• The liver findings were the surprise result: near-complete resolution of metabolic dysfunction-associated steatotic liver disease (MASLD) in most high-dose participants.

TRIUMPH-1 — general obesity and long-term extension

Long-term efficacy and safety in adults with obesity or overweight who do not have type 2 diabetes, including a prespecified extension beyond the primary endpoint.

2,339 adults without type 2 diabetes · 80 weeks, with a 104-week extension for BMI ≥ 35

28.3%

Mean weight loss (12 mg)

at 80 weeks

45.3%

Participants losing > 30% of body weight

30.3%

Mean weight loss at extension endpoint

week 104, BMI ≥ 35 cohort

• The largest reported average weight reduction for a pharmacological agent to date, in a range previously associated with bariatric surgery.
• Weight loss had not fully plateaued at 80 weeks — the extension cohort continued to lose weight through week 104.
• This is the trial that establishes the ceiling of the triple-agonist approach in a non-diabetic population.

TRIUMPH-2 — obesity with type 2 diabetes

Whether the weight effect holds up in people with type 2 diabetes, and what happens to glycaemic control at the same time.

Adults with obesity and type 2 diabetes · once-weekly dosing · 80 weeks

up to 20.8%

Mean weight reduction

at 80 weeks

Significant reduction

HbA1c

versus comparator

• As is typical in this class, weight loss in a diabetic population is smaller than in a non-diabetic one — but still substantially larger than existing options.
• Glycaemic improvement occurred alongside the weight change rather than at its expense, which matters for the dual metabolic use case.

TRIUMPH-3 — severe obesity with cardiovascular disease

A higher-risk population: people with severe obesity who already have established atherosclerotic cardiovascular disease.

Adults with severe obesity and established ASCVD · 80 weeks

22.6%

Mean weight reduction (high dose)

at 80 weeks

Broad improvement

Cardiovascular risk factors

systolic BP, triglycerides, non-HDL cholesterol

• Effect size held in the population where the metabolic burden is heaviest and comorbidity risk is highest.
• Improvements spanned several independent cardiovascular risk markers rather than a single endpoint.

TRIUMPH-4 — obesity with knee osteoarthritis

Whether large weight reduction translates into measurable mechanical and inflammatory relief in people with obesity and severe knee osteoarthritis.

Adults with obesity and severe knee osteoarthritis · 68 weeks

28.7%

Mean weight loss

75.8%

Reduction in osteoarthritis pain

WOMAC pain subscale

≈ 1 in 8

Participants reporting no pain at study end

• The pain result is larger than load reduction alone would predict, which is why the inflammatory component is being examined.
• This is the trial most relevant to musculoskeletal research questions rather than purely metabolic ones.

TRIUMPH-5 — head-to-head versus tirzepatide

A direct comparative study pitting retatrutide against tirzepatide in a diabetes population, designed to formally establish whether triple agonism outperforms dual agonism.

Active comparator, head-to-head against tirzepatide · diabetes population

• No results have been reported. Cross-trial comparisons between retatrutide and tirzepatide figures are not valid evidence — this trial exists precisely because that comparison cannot be made indirectly.
• It is the single most informative upcoming readout for anyone tracking the multi-agonist class.