Summary: In a SURMOUNT-1 post-hoc analysis, most people who lost less than 5% of body weight on tirzepatide by week 12 still reached that threshold with continued treatment, with 90% achieving at least 5% loss by week 72, supporting extending therapy well beyond an early checkpoint.
PICO Summary
| Element | Detail |
|---|---|
| Population | 1545 tirzepatide-treated SURMOUNT-1 participants with obesity/overweight; 278 (18%) late responders, 1267 (82%) early responders. |
| Intervention | Continued tirzepatide (5, 10, or 15 mg) beyond the 12-week response checkpoint, assessed to weeks 24 and 72. |
| Comparison | Late responders (<5% loss at week 12) versus early responders (≥5% at week 12). |
| Outcome | Among late responders, 70% reached ≥5% weight loss by week 24 and 90% by week 72; mean time to 5% loss was 24.8±12.7 weeks. Higher doses gave higher proportions reaching weight thresholds. Late responders were more often male with higher baseline weight, BMI, and waist. |
Expert Commentary
This is a clinically useful analysis that speaks directly to a decision I face in practice: what to do when a patient has not hit the conventional early weight-loss milestone. The traditional stopping rules for appetite-suppressant therapy, often a 5% loss by three months, were derived from older, less effective agents, and this post-hoc work suggests they may be the wrong yardstick for the incretin class. The striking number is that 90% of so-called late responders eventually reached at least 5% loss by week 72, with the average late responder simply taking about 25 weeks rather than 12 to get there. That argues for patience and continued titration rather than early abandonment. The honest caveats: this is a secondary analysis, 5% is itself a modest threshold, and late responders started heavier, so some of the delayed trajectory reflects baseline differences. Can I use this with my patients? Yes, concretely. It supports not discontinuing tirzepatide at 12 weeks for a patient who is tolerating it and trending in the right direction, and instead optimising the dose and reassessing later, while still applying judgement about genuine non-response and side-effect burden.
References
Ard J, Lee CJ, Gudzune K, et al. Weight reduction over time in tirzepatide-treated participants by early weight loss response: post hoc analysis in SURMOUNT-1. Diabetes Obes Metab. 2025;27(9):5064–5071. doi:10.1111/dom.16554