Constipation on Zepbound (tirzepatide): Week-by-Week Timeline of What to Expect

What the label reports about constipation

In the pooled weight-management trials (adults with obesity or overweight, with or without type 2 diabetes, up to 72 weeks), constipation including hard stools was reported by 5% on placebo, 17% at 5 mg, 14% at 10 mg and 11% at 15 mg [1]. Each figure is the proportion of that dose group reporting the event at some point during the trial [1].

The dose schedule is not a symptom schedule

Weeks 1 to 4 are the 2.5 mg starting period and 5 mg begins at week 5, with later increases of 2.5 mg after at least 4 weeks on the current dose [1]. Maintenance doses for weight reduction are 5, 10 or 15 mg; 2.5 mg is for initiation only [1]. The label says to consider treatment response and tolerability when selecting the maintenance dose, and a lower one if a maintenance dose is not tolerated [1].

What the label does say about timing

Tirzepatide delays gastric emptying, and the delay is largest after the first dose and diminishes over time [1]. The majority of nausea, vomiting and diarrhea events occurred during dose escalation and decreased over time; constipation is not named in that sentence [1].

The label reports severe gastrointestinal adverse reactions in 1.7% at 5 mg, 2.5% at 10 mg and 3.1% at 15 mg versus 1% on placebo, and says Zepbound is not recommended in patients with severe gastroparesis [1]. It also warns of acute pancreatitis, which may include persistent or severe abdominal pain sometimes radiating to the back [1].

What NIDDK suggests tracking

The NIDDK suggests tracking bowel movements and stool appearance for several days or weeks, and lists symptoms that include fewer than three bowel movements a week, hard or lumpy stools, difficult or painful passage, and a feeling that not all stool has passed [2][3]. It also notes that iron supplements, calcium channel blockers, diuretics, antacids containing aluminum or calcium, and narcotic pain medicines can worsen constipation [3].