In the SURMOUNT-1 trial (New England Journal of Medicine, 2022), adults without diabetes who took tirzepatide 15mg alongside diet and activity advice lost an average of 20.9% of their body weight over 72 weeks, compared with 3.1% on placebo, counting everyone who started treatment. Among people who stayed on treatment, the average was 22.5%. On 15mg, 91% lost at least 5% of their weight, compared with 35% on placebo. Individual results vary. But "working" doesn't mean losing weight every single week. If the scale has stopped moving, there's almost always an identifiable reason. Here are the real ones, roughly in order of how often they turn out to be the answer.
1. You haven't reached an effective dose yet
The most common explanation. 2.5mg is a starting dose designed for tolerance, not a treatment dose. In the SURMOUNT-1 trial (New England Journal of Medicine, 2022), 2,539 adults without diabetes lost an average of 15.0% of their body weight on tirzepatide 5mg, 19.5% on 10mg and 20.9% on 15mg over 72 weeks, compared with 3.1% on placebo, counting everyone who started treatment. Among people who stayed on treatment, the averages were 16.0%, 21.4% and 22.5%. Individual results vary. If you're early in titration you may simply not be there yet.
2. A genuine plateau, which is normal
Weight loss is not linear. As you lose weight, your body needs fewer calories, so the deficit that was working shrinks. Plateaus are common and don't mean the medicine has stopped working.
3. Protein and muscle
Losing muscle alongside fat lowers resting metabolic rate and makes further loss harder. If intake has dropped sharply without protein being prioritised, this is likely contributing. Weight on the scale is also a poor measure here. You can lose fat and gain muscle with little scale movement.
4. What you're eating when appetite returns
Appetite suppression fades toward the end of the weekly cycle for some people, and intake in those days can quietly offset the rest of the week.
5. Fluid retention and measurement noise
Salt, carbohydrate intake, menstrual cycle and exercise all shift water weight by several pounds. Weigh under consistent conditions and judge the trend over weeks, not days.
6. Sleep, stress and alcohol
All three affect appetite regulation and adherence. Alcohol also adds significant calories and worsens GI side effects.
7. Other medicines and medical causes
Some medicines promote weight gain, and undiagnosed hypothyroidism and other endocrine causes exist. If loss has genuinely stalled at an adequate dose with good adherence, this deserves review.
What to do about it
- Track measurements and how clothes fit rather than weight alone.
- Prioritise protein at every meal.
- Add resistance training to protect muscle.
- Discuss a dose review with your prescriber before assuming it's not working.
- Give any change at least four weeks before judging it.
In practice, "Mounjaro isn't working" almost always turns out to be either an under-dosed patient or a genuine plateau being read too soon. In the SURMOUNT-1 trial (New England Journal of Medicine, 2022), adults without diabetes who took tirzepatide 15mg alongside diet and activity advice lost an average of 20.9% of their body weight over 72 weeks, compared with 3.1% on placebo, counting everyone who started treatment. Among people who stayed on treatment, the average was 22.5%. On 15mg, 91% lost at least 5% of their weight, compared with 35% on placebo. Individual results vary.
See also Mounjaro weight loss by week, what to eat on Mounjaro and Mounjaro vs Wegovy.