Can tirzepatide (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist) cause acid indigestion?

Tirzepatide and Acid Indigestion

Yes, tirzepatide commonly causes acid indigestion (dyspepsia) as a gastrointestinal side effect. Dyspepsia is a well-documented adverse effect of tirzepatide, with clinical evidence showing significantly higher rates compared to placebo and insulin therapies 1.

Gastrointestinal Side Effects of Tirzepatide

Tirzepatide, a dual GIP/GLP-1 receptor co-agonist, affects the gastrointestinal system through several mechanisms:

1. Delayed gastric emptying: Tirzepatide slows gastric emptying by inhibiting gastric peristalsis while increasing pyloric tone 2. This mechanism is primarily mediated through vagal nerve pathways.

2. Reduced gastric acid secretion: The drug reduces gastric acid secretion, which can paradoxically lead to symptoms of indigestion in some patients 2.

3. Altered gastrointestinal motility: Tirzepatide affects the entire GI tract, potentially causing various digestive symptoms 2.

Incidence of Dyspepsia with Tirzepatide

Meta-analysis data shows:

• The incidence rate of dyspepsia in patients receiving tirzepatide was 7.13%, compared to 3.31% in control groups 1
• Tirzepatide significantly increases the risk of dyspepsia compared to placebo and insulin (RR, 2.52; 95% CI, 1.58 to 4.01; P ≤ 0.0001) 1
• Higher doses of tirzepatide (15mg) are associated with increased risk of dyspepsia compared to lower doses 3

Other Related Gastrointestinal Side Effects

Tirzepatide is also associated with other GI side effects that may contribute to or be confused with acid indigestion:

• Nausea: 20.43% incidence (vs. 10.47% in comparators) 1
• Vomiting: 9.05% incidence (vs. 4.86% in comparators) 1
• Decreased appetite: 9.64% incidence (vs. 2.88% in comparators) 1
• Diarrhea: 16.24% incidence (vs. 8.63% in comparators) 1
• Constipation: 2.54% incidence (vs. 0.856% in comparators) 1

Clinical Implications

1. Dose-dependent relationship: The incidence of GI adverse events, including dyspepsia, is positively correlated with tirzepatide dose 3.

2. Time-dependent improvement: GI side effects of tirzepatide tend to decrease gradually over time, suggesting that long-term steady medication may reduce these effects 3.

3. Medication absorption: The American Diabetes Association notes that tirzepatide may affect the absorption of oral medications, particularly those with narrow therapeutic indices or those dependent on threshold concentrations 2.

Management Strategies

For patients experiencing acid indigestion with tirzepatide:

1. Dose titration: Start with lower doses and gradually increase to minimize GI side effects
2. Meal timing: Take with or after meals to reduce GI symptoms
3. Hydration: Maintain adequate fluid intake
4. Monitor: Watch for signs of more severe GI complications, such as severe constipation or small bowel obstruction/ileus progression 2

Conclusion

Acid indigestion is a recognized side effect of tirzepatide therapy, occurring in approximately 7% of patients. The effect appears to be dose-dependent and tends to improve over time with continued use. While uncomfortable, this side effect rarely requires discontinuation of therapy unless severe or persistent.