Zepbound (Tirzepatide) and Constipation: When to Call Your Doctor

How Common Is Constipation on Zepbound?

The Zepbound label pools two placebo-controlled weight-management trials covering 958 people on placebo and 630, 948 and 941 people on 5, 10 and 15 mg, treated for up to 72 weeks [1]. Constipation, a category that includes hard stools, was reported by 17% at 5 mg, 14% at 10 mg and 11% at 15 mg, versus 5% on placebo [1]. The figure is highest at the lowest maintenance dose rather than rising step by step with dose.

Other digestive effects in the same pool follow a different shape. Nausea was reported by 25%, 29% and 28% versus 8% on placebo, and diarrhea by 19%, 21% and 23% versus 8% [1]. Any gastrointestinal adverse reaction was reported by 56% of people at every Zepbound dose, versus 30% on placebo, and 1.9% on 5 mg, 3.3% on 10 mg and 4.3% on 15 mg stopped treatment for a digestive reason, versus 0.5% on placebo [1]. The label states that the majority of nausea, vomiting and diarrhea events occurred during dose escalation and decreased over time [1].

Warning Signs NIDDK Lists With Constipation

NIDDK lists these symptoms as ones that call for seeing a doctor right away when constipation is also present: bleeding from the rectum, blood in the stool, constant pain in the abdomen, inability to pass gas, vomiting, fever, lower back pain, and losing weight without trying [2]. NIDDK also says to see a doctor if constipation does not go away with self-care, or if there is a family history of colon or rectal cancer [2].

What the Zepbound Label Flags

Severe gastrointestinal adverse reactions were reported by 1.7% of people on 5 mg, 2.5% on 10 mg and 3.1% on 15 mg, versus 1% on placebo, and the label states that Zepbound is not recommended in patients with severe gastroparesis [1].

The label also describes acute kidney injury from volume depletion, with most reported cases occurring in people who had nausea, vomiting or diarrhea leading to dehydration; it instructs monitoring of renal function in patients reporting reactions that could cause volume depletion, especially during starting and dose increases [1]. For pancreatitis, the label describes persistent or severe abdominal pain, sometimes radiating to the back, which may or may not come with nausea or vomiting, and says to discontinue Zepbound if pancreatitis is suspected [1].

On dose, the label says to consider treatment response and tolerability when selecting a maintenance dose, and to consider a lower maintenance dose if a maintenance dose is not tolerated [1]. It also states that the 2.5 mg starting dose is for initiation and is not approved as a maintenance dose; maintenance doses for weight reduction are 5, 10 or 15 mg once weekly [1].

What an Evaluation May Involve

NIDDK says doctors ask how often you have a bowel movement, how long symptoms have lasted, what the stools look like, whether there is blood, and about eating habits, physical activity, and medicines and supplements, and it suggests tracking bowel movements and stool appearance for several days or weeks [4]. A physical exam may check for dehydration and abdominal swelling, tenderness or masses, and tests are used when symptoms warrant them; NIDDK notes that a doctor may first try a treatment before using tests [4]. NIDDK lists calcium channel blockers, diuretics, iron supplements, narcotic pain medicines, anticholinergics and antispasmodics, anticonvulsants, and some medicines used to treat depression or Parkinson's disease among the medicines that can make constipation worse [2].

What Do the Guideline and the MiraLAX Label Say About Laxatives?

The American Gastroenterological Association and American College of Gastroenterology guideline on chronic idiopathic constipation in adults makes strong recommendations for polyethylene glycol, sodium picosulfate, linaclotide, plecanatide and prucalopride, and conditional recommendations for fiber, lactulose, senna, magnesium oxide and lubiprostone [3]. That guideline covers chronic idiopathic constipation, not constipation caused by tirzepatide [3].

The over-the-counter MiraLAX (polyethylene glycol 3350) label directs adults and children 17 and older to use 17 g once a day, stirred into 4 to 8 ounces of beverage, and limits self-use to no more than 7 days [5]. The same label lists rectal bleeding, or nausea, bloating, cramping or abdominal pain that gets worse, as possible signs of a serious condition [5].