What is the relationship between dulaglutide (Trulicity) treatment and the development of diarrhea?

From the Guidelines

Dulaglutide treatment is associated with a risk of diarrhea, which is a common adverse effect that can be managed with hydration, over-the-counter medications, and dietary modifications, as evidenced by the 2020 expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes 1. When experiencing diarrhea while taking dulaglutide, it is essential to stay well-hydrated by drinking plenty of fluids. For mild to moderate diarrhea, over-the-counter medications like loperamide (Imodium) 2mg after each loose stool (maximum 8mg daily) can help manage symptoms. Some key points to consider when managing diarrhea associated with dulaglutide treatment include:

• Dietary modifications, such as eating smaller, more frequent meals, avoiding spicy foods, caffeine, and high-fat foods, and temporarily reducing fiber intake, can help alleviate symptoms.
• The diarrhea occurs because dulaglutide, a GLP-1 receptor agonist, slows gastric emptying and affects gut motility as part of its mechanism for blood glucose control, as noted in the study 1.
• Most patients find that gastrointestinal side effects, including diarrhea, peak within the first 2-3 weeks of treatment and gradually subside over 4-8 weeks as tolerance develops.
• If diarrhea is severe, persistent beyond 8 weeks, or accompanied by signs of dehydration (excessive thirst, dry mouth, decreased urination, dizziness), contact your healthcare provider, as dose adjustment or medication change may be necessary, considering the guidelines for dose modifications and contraindications outlined in the study 1.

From the FDA Drug Label

Table 1: Adverse Reactions in Pool of Placebo-Controlled Trials That Occurred in ≥5% of TRULICITY-Treated Adult Patients with Type 2 Diabetes Mellitus a Includes diarrhea, fecal volume increased, frequent bowel movements. ... Adverse ReactionPlacebo (N=568) %TRULICITY 0.75 mg (N=836) %TRULICITY 1. 5 mg (N=834) % ... Diarrheaa6.7 8.9 12.6

Diarrhea with dulaglutide treatment is a common adverse reaction.

• The incidence of diarrhea was 6.7% with placebo, 8.9% with TRULICITY 0.75 mg, and 12.6% with TRULICITY 1.5 mg.
• In another clinical trial, the incidence of diarrhea was 7.0% with TRULICITY 1.5 mg, 11.4% with TRULICITY 3 mg, and 10.7% with TRULICITY 4.5 mg 2.

From the Research

Diarrhoea with Dulaglutide Treatment

• Dulaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used to treat type 2 diabetes, and it has been associated with gastrointestinal-related adverse events, including diarrhea 3, 4.
• The incidence of diarrhea with dulaglutide treatment is highest soon after initiation of treatment and tends to decline over time, even with dose escalation 5.
• Most cases of diarrhea associated with dulaglutide are mild to moderate in severity, and severe cases are rare 5.
• Treatment discontinuation due to diarrhea is low, and the tolerability profile of dulaglutide is consistent across different doses 5.

Management of Diarrhoea

• Loperamide is a safe and effective antidiarrheal agent that can be used to treat acute diarrhea 6.
• In cases of refractory chemotherapy-related diarrhea, intravenous steroids may be effective in reducing symptoms 7.
• The use of non-absorbing corticosteroids, such as budesonide, may not be effective in all cases of diarrhea, and alternative treatments may be necessary 7.

Dulaglutide and Gastrointestinal Tolerability

• The AWARD-11 trial assessed the gastrointestinal tolerability of dulaglutide at once-weekly doses of 1.5,3.0, and 4.5 mg, and found that the highest incidences of nausea, vomiting, and diarrhea were primarily observed soon after initiation of treatment 5.
• The incidence of gastrointestinal adverse events declined over time, and most events were mild to moderate in severity 5.
• The tolerability profiles of dulaglutide 3.0 mg and 4.5 mg were consistent with that of the 1.5-mg dose 5.