Fatigue rates by source
The Canadian monograph is the only Mounjaro® label that gives dose-by-dose fatigue rates against placebo. Its Table 2 lists reactions seen in at least 1% of adults with type 2 diabetes, drawn from the same two placebo-controlled trials the US label uses and from all seven phase 3 trials [4]. In the US label, the main table counts only reactions reaching 5%, which fatigue did not, so it appears in the text instead: in SURPASS-CVOT, 10% of people on Mounjaro® reported it [1].
SURPASS-CVOT enrolled 13,299 adults with type 2 diabetes and established heart or blood vessel disease, compared Mounjaro® up to 15 mg with dulaglutide 1.5 mg, and followed them for a median of 210 weeks [1]. The participants were older (mean age 64) and many took insulin, sulfonylureas, beta blockers and other heart medicines [1], which matters when reading the higher figure.
The European label groups fatigue, asthenia (weakness), malaise and lethargy under one term. It rates the group as very common (more than 1 in 10) in SURPASS-CVOT and common (up to 1 in 10) in the diabetes, weight-management, sleep apnea and heart failure trials [3]. The same molecule’s US weight-reduction label reports fatigue in 5% to 7% on tirzepatide against 3% on placebo [5].
| Trial pool | Placebo | 5 mg | 10 mg | 15 mg |
|---|---|---|---|---|
| Placebo-controlled diabetes trials (Canada) | 0% | 3.0% | 2.5% | 4.1% |
| All seven phase 3 diabetes trials (Canada) | — | 3.3% | 3.9% | 6.1% |
Studies that look at energy from another angle
Not every study points towards more tiredness. In SURMOUNT-OSA, two 52-week trials of tirzepatide in adults with obstructive sleep apnea and obesity, people who felt fatigued at the start reported larger gains in vitality and daily activity on tirzepatide than on placebo [6]. That is a different population from most Mounjaro® users, and it measured how people felt overall, not fatigue as a side effect.
At the serious end, a 2026 case report described a man whose fatigue, muscle aches and dark urine worsened over two weeks after he had recently started tirzepatide; he was diagnosed with rhabdomyolysis, a breakdown of muscle tissue [7]. A single case cannot show how often this happens or prove the medicine caused it, but it is a reminder that tiredness with those companions should not be ignored.
Why Mounjaro® can leave you tired
Supported by the labels: decreased appetite affected 5% to 11% of people on Mounjaro® in the US trials against 1% on placebo, and 17% in SURPASS-CVOT [1]. Eating much less than usual can lower energy. Vomiting, diarrhea and drinking less can lead to dehydration, which the labels link to kidney injury [1][3]; listlessness is among the signs of more severe dehydration [10].
Also documented: with insulin or a sulfonylurea, Mounjaro® raises the risk of low blood sugar [1]. Weakness, drowsiness and confusion are listed among its signs [2], and MedlinePlus adds tiredness [9].
Plausible but not measured: the US label says most nausea, vomiting and diarrhea happened during dose escalation and then eased [1]. If tiredness follows the same arc, it may be most noticeable in the weeks after each dose step, but no study has charted fatigue against dose steps for Mounjaro®.
Other reasons to feel worn out
MedlinePlus lists many causes of fatigue: anemia or low iron, depression, persistent pain, sleep disorders such as insomnia or sleep apnea, an underactive or overactive thyroid, diabetes, heart failure, kidney or liver disease, infections and malnutrition [8]. Medicines can contribute, including blood pressure medicines, diuretics, sleeping pills, antihistamines and steroids [8].
That list overlaps heavily with type 2 diabetes care, so a new or deepening tiredness on Mounjaro® is worth reviewing as a whole rather than blamed on one medicine.
What tends to help
MedlinePlus suggests getting enough sleep, eating a balanced diet and drinking water through the day, regular exercise, relaxation techniques, a manageable schedule, and avoiding alcohol and nicotine [8]. It notes that caffeine and other stimulants are not an effective fix and can make fatigue worse when stopped, and suggests asking your clinician whether a vitamin might help rather than starting one alone [8].
With Mounjaro®, small regular meals are often easier when appetite is low, and your prescriber or a dietitian can help if eating enough is hard. If you use insulin or a sulfonylurea, checking blood sugar when you feel unusually tired or weak tells you whether a low is involved [9].
Do not change your Mounjaro® dose or skip injections because of tiredness without talking to your prescriber; any adjustment is their call.
Mounjaro® and Zepbound® are registered trademarks of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Eli Lilly and Company.
When to get help
| Sign | Who to contact | How fast | Source |
|---|---|---|---|
| Tiredness with confusion, dizziness, blurred vision or very little urine | Your clinician right away; emergency care if severe | Today | MedlinePlus [8] |
| Weak, drowsy, sweaty or shaky while on insulin or a sulfonylurea, and not better after sugar | Emergency services | Emergency | Medication Guide [2]; MedlinePlus [9] |
| Exhaustion with muscle aches and dark or cola-coloured urine | Your clinician the same day | Today | Case report [7]; MedlinePlus [8] |
| Fatigue together with vomiting or diarrhea that will not stop | Your prescriber | Today | Medication Guide [2] |
| Unexplained tiredness with fever, weight loss you did not expect, regular sweats or low mood | Your clinician | At your next appointment | MedlinePlus [8] |
