Sleep in the Zepbound® documents
The main US safety data for Zepbound® come from SURMOUNT-1 and SURMOUNT-2, two 72-week trials in adults with obesity or overweight. Their pooled table lists reactions reported by at least 2% of people on Zepbound® and more often than on placebo; insomnia, trouble falling asleep and sleep disturbance are not among them. [1] The Canadian monograph lowers the threshold to 1% for the same trials and still does not list insomnia. [3] In the EU there is no Zepbound® product; tirzepatide for weight and sleep apnea is sold as Mounjaro®, and its adverse reaction table does not include insomnia either. [4]
What the labels do contain is sleep data from the other direction. In the US label’s section 14.2, the two sleep apnea trials (published as SURMOUNT-OSA) enrolled 469 adults with obesity and moderate to severe sleep apnea, and Zepbound® improved sleep-related impairment on a standard questionnaire compared with placebo. [1] The Canadian monograph adds that sleep disturbance scores also improved at week 52. [3]
| Source | Insomnia as a side effect | Sleep findings |
|---|---|---|
| US label, Table 1, SURMOUNT-1 and -2 [1] | Not listed | Fatigue (includes lethargy, malaise) 5 / 6 / 7% on 5 / 10 / 15 mg vs 3% on placebo |
| US label, SURMOUNT-OSA trials [1] | Reactions similar to weight trials | Sleep-related impairment improved vs placebo; mean Epworth sleepiness score at entry about 10 |
| Canadian monograph [3] | Not listed (≥1% table) | Sleep-related impairment and sleep disturbance improved vs placebo at week 52 |
| EU, tirzepatide sold as Mounjaro® [4] | Not listed | Sleep apnea trial results described in section 5.1 |
| NEJM report of SURMOUNT-OSA [5] | Gastrointestinal events most frequent, mostly mild to moderate | Apnea-hypopnea index fell by 25.3 and 29.3 events/hour vs about 5 on placebo |
Trials and records studies
A detailed analysis of the SURMOUNT-OSA questionnaires found that, after 52 weeks, people on tirzepatide reported better scores than placebo for sleep-related impairment, sleep disturbance, daily functioning and quality of life; in the trial without breathing machines, daytime sleepiness scores also improved. [6] These were people with sleep apnea, for whom better breathing at night is expected to help sleep, so the finding does not automatically carry over to everyone using Zepbound® for weight.
Real-world records give a less tidy picture. In a US electronic health record network, adults without type 2 diabetes who started tirzepatide had a slightly higher hazard of an insomnia diagnosis than those starting semaglutide (hazard ratio 1.13). [7] The authors note that their results remain subject to confounding and misclassified diagnoses. In adolescents with obesity, a separate records study found no significant difference in insomnia between incretin medicines, including tirzepatide, and lifestyle treatment. [8] Zepbound® is not approved for children, and neither study was a randomised trial.
What might be waking you
The label gives no mechanism for insomnia, because it does not describe insomnia. It does describe several things that can break up a night.
- Reflux and indigestion. Both were more frequent on Zepbound® than on placebo, [1] and MedlinePlus notes that reflux symptoms can be worse after eating, when lying down and at night. [12]
- Nausea and stomach upset during dose steps. Most nausea, vomiting and diarrhea occurred while the dose was being raised, then eased. [1] Each step comes after at least 4 weeks on the previous dose. [1]
- Low blood sugar. In people with type 2 diabetes, especially those also taking a sulfonylurea or insulin, Zepbound® can cause low blood sugar, [1] and MedlinePlus lists trouble sleeping among its symptoms. [13]
- Sleep apnea that is not yet controlled. The National Heart, Lung, and Blood Institute lists insomnia among sleep apnea symptoms, along with waking to urinate and morning headache. [9]
Causes that have nothing to do with the injection
MedlinePlus describes short-term insomnia as common and usually triggered by stress, family pressure or a difficult event. Ongoing insomnia is often a symptom of something else: medical conditions, medicines, other sleep disorders, or caffeine, tobacco and alcohol. [10] Depression, night or shift work and long-distance travel across time zones all raise the risk. [10]
Starting a weight treatment can bring several of these together: new routines, a changed meal pattern, more evening exercise, or worry about side effects. It is also worth reviewing any other medicine, supplement or diet product you take, which MedlinePlus specifically suggests asking about. [11]
Practical steps from general sources
The Zepbound® Medication Guide has no sleep-specific advice. It does allow the injection at any time of day and lets you shift your injection day provided 72 hours or more separate two doses, [2] which can help if the first day after a dose is your hardest; plan any change with your prescriber.
MedlinePlus’s sleep-habit guidance includes going to bed and getting up at about the same times, avoiding caffeine and alcohol in the evening, skipping heavy meals for at least 2 hours before bed, keeping the bedroom quiet and dark, and getting up to do something quiet if you cannot fall asleep within 30 minutes. [11] For night-time reflux it adds raising the head of the bed and eating dinner 2 to 3 hours before sleep. [12] Cognitive behavioural therapy is a recognised treatment for ongoing insomnia. [10] If you use a positive airway pressure machine, keep using it as prescribed: the Canadian patient information says Zepbound® does not replace it and that changes are your clinician’s call. [3]
Zepbound® and Mounjaro® 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 |
|---|---|---|---|
| Night sweats, shakiness, confusion or a pounding heart that wake you, especially on insulin or a sulfonylurea | Treat as possible low blood sugar; tell your prescriber | Today | Medication Guide [2]; MedlinePlus [13] |
| Severe stomach pain at night that will not go away, sometimes reaching the back | Stop Zepbound® and call your prescriber right away | Today | Medication Guide [2] |
| Feeling sad or depressed, or pain or discomfort keeping you awake | Contact your health care provider | At your next appointment | MedlinePlus [11] |
| Loud snoring, gasping, morning headaches or daytime sleepiness despite treatment | Discuss sleep apnea control with your clinician | At your next appointment | NHLBI [9] |
| Insomnia lasting a month or longer, or using sleep medicines without advice | Raise at your next visit | At your next appointment | MedlinePlus [10][11] |
