Research brief · 2026-09-09
How Much Weight Do People Actually Lose Outside of Clinical Trials?
The headline numbers from the pivotal trials are well known. In STEP 1, published in the New England Journal of Medicine in 2021, 1,961 adults on weekly semaglutide lost an average of 14.9 percent of body weight over 68 weeks, against 2.4 percent on placebo. In SURMOUNT-1, published in 2022, the highest dose of tirzepatide produced 20.9 percent over 72 weeks. Both are prescription medications, and both trials came with close monitoring, structured dose escalation and strong incentives to stay enrolled.
Real-world results are consistently smaller. A 2026 narrative review by Bloomgarden in the Journal of Diabetes set seven meta-analyses covering 127 randomised trials against 26 real-world studies found through a structured search. In people with type 2 diabetes, real-world semaglutide use over six to twelve months produced roughly 4.7 to 10.5 kilograms of weight loss, below the trial estimates. The gap was not mysterious. Only 13 percent of real-world semaglutide users ever reached the 2.4 milligram dose used in the STEP trials, and only about a quarter of tirzepatide users reached the top SURMOUNT dose. On top of that, 20 to 50 percent of people discontinued within a year.
When analyses restricted themselves to people who stayed on treatment, the gap mostly closed. In the SHAPE real-world study cited by the review, persistent semaglutide users lost 14.1 percent and persistent tirzepatide users 16.5 percent, close to the trial figures. A 2026 electronic-record study by Venkatakrishnan and colleagues in PNAS Nexus matched 20,678 tirzepatide and semaglutide patients and found mean maximum weight loss over two years of 14.7 percent and 10.8 percent respectively, with tirzepatide patients about twice as likely to lose 15 percent or more in the first year.
The picture, then, is not that the drugs work less well outside trials. It is that fewer people outside trials reach the studied dose and stay on it, and population averages reflect that. Persistence also appears to be improving: a 2026 claims analysis found one-year persistence rose from about a third of people starting in 2021 to about six in ten starting in early 2024.
What the evidence cannot yet say is who will end up in the group that reaches trial-level results and who will not. Individual predictors are poorly characterised, most real-world cohorts run two years or less, and records-based studies miss anyone sourcing medication outside the tracked system. These are prescription medications, and questions about expected results for any individual belong with a physician.
Sources
- Bloomgarden Z. Real-World vs. Randomized Trial Evidence for Incretin-Based Therapies: A Narrative Review
- Journal of Diabetes 2026
- Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)
- New England Journal of Medicine 2021
- Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)
- New England Journal of Medicine 2022
- Venkatakrishnan AJ, Murugadoss K, Soundararajan V. Weight-loss dynamics with tirzepatide versus semaglutide
- PNAS Nexus 2026
Peptide Proof reports what studies found. We do not give medical advice, dosing guidance, or treatment recommendations.