Zepbound® and constipation

Hard stools count, and so does placebo

A footnote under Table 1, repeated in Canada’s Table 2, says the constipation row combines two reported terms: constipation and hard feces ^[1][3]. Anyone who noted either at least once during the 72-week trials is counted, however briefly. The pooled trials are SURMOUNT-1 (no diabetes) and SURMOUNT-2 (type 2 diabetes) ^[1].

The placebo column is not a group living as usual. Everyone in these trials, on Zepbound® or placebo, was counselled to eat about 500 kcal a day less than they needed and to aim for at least 150 minutes of activity a week ^[1]. A 5% placebo rate therefore reflects people given the same diet advice, and the extra constipation on Zepbound® sits on top of that.

A dose line that runs backwards

Nausea, diarrhea, vomiting, abdominal pain and indigestion all hold steady or rise from 5 mg to 15 mg in Table 1. Constipation goes the other way: the 5 mg group reported it most and the 15 mg group least, although every dose stayed well above placebo ^[1]. At 5 mg, constipation (17%) and diarrhea (19%) were reported at almost the same rate; at 15 mg, diarrhea (23%) was about twice as common as constipation (11%) ^[1].

The label offers no explanation, and the columns were not built from the same people. SURMOUNT-2 had no 5 mg arm, so that column holds only SURMOUNT-1 participants without diabetes, while the 10 mg and 15 mg columns mix both trials; Canada marks the 5 mg column “SURMOUNT-1 only” ^[1][3]. The pattern belongs to these trial groups. It is not a forecast of what a dose change will do for one person, and no source suggests changing dose to influence it.

Timing and stopping: what the label leaves out

For nausea, vomiting and diarrhea, the label says most events came during dose escalation and eased later ^[1]. Constipation is not named in that sentence, and no separate timing is given, so assuming it follows the same early pattern would be guesswork. There is no stopping rate for constipation alone either; stomach and bowel reactions together led 1.9% to 4.3% of people on Zepbound® to stop, against 0.5% on placebo ^[1].

Canada’s overview of three placebo-controlled weight trials lists constipation among the most frequent reactions, alongside nausea, diarrhea and vomiting, and describes these as generally mild or moderate ^[3].

If you use Zepbound® for sleep apnea

Zepbound®’s second US use is obstructive sleep apnea (moderate or severe) in adults living with obesity, with 10 mg or 15 mg as the maintenance dose ^[1]. The two sleep apnea trials, with 467 adults, did not get their own row in the US table; the label says their reactions were similar to the weight trials ^[1]. The published report of those 52-week trials found stomach and bowel events to be the most common, mostly mild to moderate ^[6].

The European information is more specific: its frequency footnote for constipation places the sleep apnoea trials, together with the weight-management trials, in the very common band, meaning more than 1 in 10 people ^[4]. If you started Zepbound® for sleep apnea, constipation is therefore an expected possibility rather than a sign that something unusual is happening.

How tirzepatide could hold things up

Label-backed: the stomach empties more slowly on tirzepatide, especially after the first injection, and people eat less ^[1]. Neither effect is tied to constipation in the label itself ^[1].

What reviewers propose: a 2025 review that looked at constipation among other stomach symptoms of obesity treatment attributes these effects mainly to altered motility and hormone-driven changes in appetite, and lists slow dose titration, dietary counselling and supportive medicines as common strategies ^[7]. It summarises other studies and did not measure bowel transit on tirzepatide.

General background: NIDDK lists slow movement of stool through the colon, changes in how much and what you eat, too little fluid, too little physical activity and conditions such as diabetes among causes of constipation, and notes that several can act at once ^[8].

Impaction, ileus and blockage

Section 6.2 of the US label collects reports made after approval: severe constipation including fecal impaction, ileus and intestinal obstruction ^[1]. Canada lists ileus among its post-market reactions, and its patient information describes ileus as a loss of muscle contraction in the intestine, with bloating, abdominal pain and cramping, gas, nausea, vomiting, constipation and loss of appetite ^[3]. Separately, section 5.2 reports severe stomach and bowel reactions in 1.7%, 2.5% and 3.1% on the three doses, against 1% on placebo ^[1].

MedlinePlus describes fecal impaction as a large lump of dry, hard stool stuck in the rectum, usually after a long spell of constipation ^[11]. Its signs include cramping and bloating, straining, small semi-formed stools, rectal bleeding and, confusingly, leakage of liquid stool or sudden watery diarrhea in someone who has been constipated ^[11]. Bowel obstruction brings a swollen, full abdomen, cramping pain, nausea and vomiting and an inability to pass gas or stool ^[12].

Other things that slow the bowel

NIDDK names medicines and supplements that can make constipation worse, among them antacids containing aluminium or calcium, anticholinergic and antispasmodic drugs, anticonvulsants, Parkinson’s medicines and some antidepressants ^[8]. MedlinePlus adds that anti-diarrhea medicines taken too often slow the passage of stool, as do narcotic painkillers ^[11]. Routine changes count as well: ignoring the urge to go, switching medicines or changing how much and what you eat ^[8].

Some causes need a doctor rather than self-care. NIDDK advises prompt review for constipation with bleeding from the rectum, constant abdominal pain or weight loss you were not trying for, and a check-up for symptoms that do not respond to self-care or for a family history of colon or rectal cancer ^[8]. Conditions such as an underactive thyroid can also cause constipation ^[8].

What general guidance suggests

The Zepbound® documents give no self-care advice for constipation, so the steps below come from NIDDK and MedlinePlus. Talk them through with your prescriber, especially if you have kidney disease or a fluid limit.

• Bring in fibre-rich foods such as berries, apples with the skin on, oranges, pears, carrots, broccoli, peas and nuts, and cut back on low-fibre prepared and processed foods ^[10].
• Drink water and other liquids, such as clear soups, so the fibre works better; ask a health professional how much is right for you ^[10].
• Keep active, give yourself time on the toilet, go when you feel the urge, and try resting your feet on a footstool ^[9].
• A health professional may suggest a short course of a laxative and will say which type: fibre supplements, osmotic agents, stool softeners, lubricants or, if constipation is severe, stimulants ^[9]. Because Zepbound® slows stomach emptying and can affect tablet absorption, ask a pharmacist before adding one ^[1].
• Do not stop a prescribed medicine you suspect is contributing without speaking to the person who prescribed it ^[9].

Zepbound® and Mounjaro® are registered trademarks of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Eli Lilly and Company.