Annals of Internal Medicine published an updated systematic review on 1 September 2026 covering GLP-1 receptor agonists and co-agonists for weight loss in adults without diabetes. Thirty-eight randomised trials, 25,816 participants, fourteen trials newer than the previous version.
The number that will travel is the one for retatrutide: 22.1 percent placebo-subtracted weight loss.
The sentence that will not travel is in the limitations, and it changes how the whole table should be read.
A framing note. These are investigational and approved medicines and this is a review of trials in patients. Peptra Labs supplies Retatrutide as a reference material for laboratory research only, and nothing below is guidance about human use or about weight loss.
What the review found
The authors searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials from 5 October 2024 through 25 March 2026, including randomised controlled trials with treatment duration of at least sixteen weeks. Two reviewers extracted data independently. The update added fourteen new trials and eleven thousand participants to the prior review.
| Compound | Placebo-subtracted weight loss |
|---|---|
| Liraglutide | -5.8 percent, CI -8.0 to -3.6 |
| Orforglipron | -12.4 percent, CI -15.1 to -9.7 |
| Oral semaglutide | -14.3 percent, CI -17.2 to -11.4 |
| Subcutaneous semaglutide | -14.8 percent, CI -16.2 to -13.4 |
| Tirzepatide | -19.0 percent, CI -21.6 to -16.4 |
| Retatrutide | -22.1 percent, CI -24.9 to -19.3 |
| Amycretin | -23.9 percent, CI -29.3 to -18.5 |
The authors group the first five as commercially available therapies and describe the last two as emerging multiagonists showing numerically greater reductions.
On safety, gastrointestinal adverse events were common, 76.0 percent against 40.1 percent with placebo. Discontinuation due to adverse events was 10.7 percent against 3.4 percent, described as generally low but numerically higher with some oral agents. Serious adverse events were 6.5 percent against 5.2 percent and deaths 0.1 percent against 0.0 percent, with the authors reporting no new safety signals.
The limitation that reorders everything above
Under limitations the authors write that heterogeneity precluded quantitative synthesis.
That single clause means the table is not a ranking. Each figure comes from that compound’s own trials, measured against that trial’s own placebo group, in that trial’s own population, with its own duration and its own definition of who was eligible. The numbers were placed in one list. They were never compared with each other.
Two entries can differ by four percentage points because one drug works better, or because one enrolled heavier participants, or ran longer, or had a placebo group that lost more, or used a different analysis population. A systematic review that declines to pool is telling you it could not distinguish those explanations.
The authors’ own word for the multiagonist results is “numerically greater”, which is precise and deliberately weaker than “greater”. Coverage that reports a league table has removed the adjective.
Where retatrutide sits in the table
Retatrutide is not commercially available anywhere. It sits in the review as an emerging multiagonist, with a confidence interval running from -19.3 to -24.9 percent.
That interval is worth reading on its own terms. The lower bound of the retatrutide interval is roughly where the tirzepatide point estimate sits, and the two intervals overlap across a wide span. On the evidence assembled here, a claim that retatrutide beats tirzepatide is not supported, and the review does not make one.
Amycretin’s interval is wider still, from -18.5 to -29.3 percent, which is what a smaller evidence base looks like. Interval width is doing as much work in this table as the point estimates are, and it is the part that gets dropped first in secondary coverage.
How this fits with the last few days
Three days ago we covered ten meta-analyses resting on one shared set of trials, where apparent agreement came from a common evidence base rather than from replication. Two days ago we covered a trial that met non-inferiority and missed superiority by one hundredth on a prespecified confidence bound.
This is the third variety of the same reading problem, and it is the most common of the three. A table invites comparison by its layout. The authors say in the text that comparison is not what the table supports.
It also connects to a post hoc analysis of composite endpoints we covered earlier, since the SURMOUNT programme is part of the evidence feeding this review. Head-to-head data exist for some pairs, and the authors report them separately: greater weight loss with semaglutide than liraglutide, and greater weight loss with tirzepatide and with cagrilintide-semaglutide than with semaglutide. Those are genuine direct comparisons, and they are the only comparative statements in the abstract.
Note which compound is absent from that list. There is no head-to-head trial reported here putting retatrutide against anything.
What this means for a laboratory
Retatrutide is not approved anywhere and has no head-to-head trial, which places it at a specific stage of evidence, and the useful thing is to name that stage precisely.
Retatrutide now has a placebo-subtracted effect size published in a general medical journal with a confidence interval attached. That is more than it had a year ago and considerably less than a comparative claim. Laboratories working with retatrutide as reference material are working ahead of the clinical record, which is normal for research chemistry and worth stating rather than blurring.
Tirzepatide is the useful contrast. It appears in this review, in a cardiovascular outcomes trial, in sleep apnoea trials and in post-marketing databases. The gap between the two catalogues of evidence is years, not months.
Our retatrutide research guide covers the receptor pharmacology, our European research buyer guide covers procurement and documentation, and everything is supplied on a research use only basis.
References
- Moiz A, Filion KB, Samuels AE, Tsoukas MA, Yu OHY, Peters TM, Eisenberg MJ. Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes: An Updated Systematic Review. Annals of Internal Medicine, 1 September 2026. doi 10.7326/ANNALS-25-05519. PROSPERO CRD42024505558
- Kow CS, Thiruchelvam K, Ramachandram DS, Zaihan AF. Weight Regain Trajectories After Discontinuation of Semaglutide or Tirzepatide: A Reconstructed Aggregate-Data Bayesian Longitudinal Meta-Analysis. Endocrinology, Diabetes and Metabolism, September 2026, 9(5):e70325
- Ramzy D, Isshak R, Patel D, et al. Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide, and Atrial Fibrillation: An Umbrella Review With Methodological Appraisal of Overlapping Meta-Analyses. Cureus, 30 July 2026, 18(7):e113641
The products referenced on this site are supplied for laboratory research use only. They are not medicines and are not intended for human or veterinary use. This article summarises published research for informational purposes and is not medical advice. Statements about third-party studies belong to their authors.
