Daily PubMed evidence board
Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial.
This randomized phase 3 trial tested retatrutide - a drug that activates three hormonal receptors (GIP, GLP-1, and glucagon) - as a once-weekly injection…
Signal score64Research triage score
CertaintyLow-to-moderateVerify in full text
PMID42250575Source identifier
Research triage, not medical advice
Do not use this summary, score, or benefit-cost estimate to diagnose, treat, prescribe, or change care without reviewing the full study and consulting qualified professionals.
Verify before acting
Check full-text methods, eligibility, outcomes, risk of bias, harms, conflicts, funding, replication, and applicability.
Plain-English signal
This randomized phase 3 trial tested retatrutide - a drug that activates three hormonal receptors (GIP, GLP-1, and glucagon) - as a once-weekly injection in adults with type 2 diabetes not controlled by diet and exercise. Over 40 weeks, participants given retatrutide (4 mg, 9 mg, or 12 mg) had larger average drops in blood sugar (HbA1c) and greater percent bodyweight loss than those given placebo. The most common side effects were mild-to-moderate gastrointestinal symptoms that tended to lessen over time. Two deaths occurred in the 4 mg group but were judged unrelated to the drug. The company Eli Lilly funded the trial.
Why it matters
- Addresses efficacy and safety of retatrutide - a triple GIP/GLP-1/glucagon receptor agonist - in adults with type 2 diabetes inadequately controlled with diet and exercise, a common clinical problem.
- Reports both glycaemic control (HbA1c change) and clinically relevant weight reduction, outcomes that drive diabetes morbidity, treatment selection, and health-system costs.
- Phase 3 randomized, double-blind, placebo-controlled evidence can change clinical and policy prioritization if results are robust and generalizable.
Primary outcomes
- Change in glycated haemoglobin (HbA1c) from baseline to week 40 (primary endpoint)
- Percentage change in bodyweight from baseline to week 40 (key secondary endpoint)
Effect summary
Per abstract (treatment-regimen estimand): mean HbA1c changes at week 40 were -1.69% (4 mg), -1.86% (9 mg), and -1.94% (12 mg) versus -0.81% with placebo, with differences versus placebo of -0.88% (4 mg), -1.04% (9 mg), and -1.12% (12 mg) (all p<0.0001). Mean percent bodyweight change was -11.5% (4 mg), -13.9% (9 mg), and -15.3% (12 mg) versus -2.6% with placebo. Most frequent AEs were mild-moderate gastrointestinal events; study drug discontinuation due to AEs was 2-5% for retatrutide and 0% for placebo. No severe hypoglycaemia reported. Two deaths occurred in the 4 mg group and were reported as unrelated to study drug.
Benefit-cost lens
| Quick take | This phase 3 RCT shows clinically meaningful reductions in HbA1c and bodyweight versus placebo; translating to benefit-cost conclusions requires local cost, baseline risk, and long-term outcome data. |
|---|---|
| BCR anchor | 2 |
| Time horizon | 3 |
| Discount rate | 0.03 |
| Assumptions | Assessment based on PubMed metadata and abstract only; full-text review required to confirm methods, subgroup effects, AE details, and long-term follow-up. |
Benefit-cost fields are assumptions-based unless explicitly source-derived. Treat them as prompts for deeper economic review.
Risk of bias
| Tool | rapid-abstract-screen |
|---|---|
| Verdict | Some concerns |
| Notes | Phase 3 randomized, double-blind, placebo-controlled design reduces bias risk, but assessment is limited to abstract-level information. Full-text review needed to evaluate randomization method, allocation concealment, handling of missing data, protocol deviations, and detailed adverse-event adjudication. |
Harms, equity, conflicts & implementation
| Implementation | Full-text review, cost data (drug price, delivery, monitoring), health-system capacity for injectable therapies, eligibility criteria translation to local populations, monitoring protocols for AEs, and budget-impact modelling. |
|---|---|
| Equity impact | Unclear from abstract. Equity effects depend on access, affordability, and differential safety/efficacy across subgroups; full-text subgroup data and implementation context required. |
| Harms | Abstract reports mostly mild-to-moderate gastrointestinal adverse events with 2-5% discontinuation due to AEs on retatrutide; no severe hypoglycaemia reported. Two deaths occurred (both in 4 mg arm) and were reported as unrelated; full-text needed for adjudication details. |
| Funding | Eli Lilly and Company |
| Registration | NCT06354660 |
| Replication | Unknown from abstract-level triage; replication in independent trials or longer-term studies not reported here. |
Source links — verify original
Use PubMed and full-text links to confirm methods, population, outcomes, harms, conflicts, and applicability.