Tiredness is one of the listed side effects of tirzepatide, the drug sold as Zepbound for weight and as Mounjaro for type 2 diabetes. The patient information for Zepbound names “feeling tired” among its most common side effects [1]. The trial numbers show how often that happened, and how much of it the placebo group also reported.
This page covers the rates, the labeled problems that can feel like fatigue, and the trial data that point the other way. The full list of reactions is in tirzepatide side effects.
How often people reported fatigue
The Zepbound label pools two placebo-controlled weight trials of up to 72 weeks [1]. Its table lists reactions seen in at least 2% of people on the drug and more often than on placebo. Fatigue is on it.
- Placebo (n = 958)3%
- Zepbound 5 mg (n = 630)5%
- Zepbound 10 mg (n = 948)6%
- Zepbound 15 mg (n = 941)7%
So about 2 to 4 extra people in 100 reported it on the drug, and the rate rose a little with each dose. A footnote matters here. The label’s “fatigue” row groups asthenia (weakness), fatigue, lethargy and malaise into one figure [1].
The Mounjaro label tells a different story for diabetes. Its table of reactions seen in at least 5% of patients in placebo-controlled trials has no fatigue row [2]. In a large heart outcomes trial that compared Mounjaro with another weekly injection, dulaglutide, fatigue was reported by 10% of people on Mounjaro. That trial had no placebo arm, so it cannot say how much of the 10% the drug caused.
What the other weight trials posted
Three more weight trials have posted adverse event tables on ClinicalTrials.gov. Each lists any event reported by at least 5% of a group, which makes the figures below direct counts rather than label summaries.
| Trial and phase | Tirzepatide | Comparator |
|---|---|---|
| SURMOUNT-3, after a lifestyle program, to week 76 | 7.0% (20 of 287) | Placebo 3.1% (9 of 292) |
| SURMOUNT-4, open-label start, weeks 0 to 36 | 6.8% (53 of 782) | None, all on the drug |
| SURMOUNT-4, randomized, weeks 36 to 92 | 2.7% (9 of 335) | Placebo 0.6% (2 of 335) |
| SURMOUNT-5, head-to-head, 72 weeks | 10.4% (39 of 374) | Semaglutide 12.2% (46 of 376) |
SURMOUNT-3 roughly doubled the placebo rate [3]. SURMOUNT-4 is the most useful for timing [4]. Everyone took tirzepatide for the first 36 weeks, and 6.8% reported fatigue. Among those then randomized to stay on it for 56 more weeks, 2.7% reported fatigue in that later stretch.
That pattern fits a side effect concentrated in the early months, though the trial was not designed to test that. In SURMOUNT-5, fatigue was slightly less common on tirzepatide than on semaglutide [5].
Labeled problems that can feel like tiredness
The labels do not explain why tirzepatide causes fatigue. They do describe three problems whose symptoms overlap with it.
Low blood sugar. The Zepbound patient information lists drowsiness and weakness among its signs [1]. In the trial of people with type 2 diabetes, it occurred in 4.2% on Zepbound against 1.3% on placebo. The rate was 10.3% in those also taking a sulfonylurea, against 2.1% in those who were not. In the trial of people without diabetes, the label reports a glucose below 54 mg/dL in 0.3%. More on the topic is in GLP-1 drugs and low blood sugar.
Low blood pressure. Hypotension occurred in 1.6% on Zepbound against 0.1% on placebo [1]. It was more common in people taking blood pressure medicine, 2.2% against 1.2%, and it also appeared alongside stomach upset and dehydration. Dizziness was reported by 4% to 5% on the drug against 2% on placebo.
Dehydration. Both labels warn that nausea, vomiting and diarrhea can cause fluid loss, and that kidney injury has been reported after it [1] [2]. The same concern for semaglutide is covered in does Ozempic cause dehydration.
Where energy improved instead
Some trial data run the other way. SURMOUNT-OSA tested tirzepatide in people with obesity and moderate to severe sleep apnea. A post-hoc analysis split them by how fatigued they felt at the start [6].
In the study of people not using a breathing machine, the fatigued group on tirzepatide improved on the SF-36 vitality scale by 8.5 points more than placebo. The non-fatigued group improved by 1.0 point more. The authors call these differences numerical, and a post-hoc split is a weaker design than a planned comparison. The sleep apnea results themselves are in Zepbound for sleep apnea.
In SURMOUNT-5, all SF-36 domains improved on both tirzepatide and semaglutide over 72 weeks [7]. Greater weight loss went with greater gains in vitality, among other domains, in the two drugs pooled.
Putting it together
Tirzepatide does cause fatigue in a minority of people: about 2 to 4 more in 100 than placebo in the main weight trials, rising with dose. The heavier reports cluster early, and the labels point to low blood sugar, low blood pressure and dehydration as overlapping problems worth ruling out.
For many people, especially those with sleep apnea, energy scores improved over a year. The dose steps that coincide with most early side effects are in tirzepatide dosage, and sleep effects of the related drug are in semaglutide insomnia. To compare prescribers, see the compounded tirzepatide rankings.