From the Guidelines
Dulaglutide can cause diarrhea in approximately 15%–20% of patients, particularly those with moderate-to-severe chronic kidney disease (CKD), but this side effect is usually tolerable with dose titration and resolves over several weeks to months. According to the study published in Kidney International in 2022 1, nausea, vomiting, and diarrhea are the most common side effects of GLP-1 receptor agonists, including dulaglutide. These symptoms are more prevalent in patients with CKD stages G3 and G4.
Some key points to consider when managing diarrhea associated with dulaglutide include:
- Staying well-hydrated to prevent dehydration
- Temporary dietary modifications, such as following a bland diet (e.g., BRAT diet: bananas, rice, applesauce, toast) and avoiding spicy, high-fat, or dairy products
- Using over-the-counter medications like loperamide (Imodium) to manage symptoms if needed
- Contacting a healthcare provider if diarrhea is severe, persistent beyond 2-3 weeks, or accompanied by signs of dehydration (excessive thirst, dark urine, dizziness)
The mechanism of dulaglutide-induced diarrhea is related to its effects on slowing gastric emptying and altering gut motility, which are part of its action to regulate blood glucose levels and promote satiety. If diarrhea is severe or persistent, a healthcare provider may recommend temporarily reducing the dose of dulaglutide or switching to another GLP-1 receptor agonist. However, it is essential to weigh the benefits of dulaglutide in managing diabetes and reducing cardiovascular and kidney disease risk against the potential side effects, as evidenced by 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 Reaction Placebo (N=568) % TRULICITY 0.75 mg (N=836) % TRULICITY 1.5 mg (N=834) % Diarrhea 6.7 8.9 12.6
- Diarrhea is a common adverse reaction associated with dulaglutide, with frequencies of 6.7% in the placebo group, 8.9% in the TRULICITY 0.75 mg group, and 12.6% in the TRULICITY 1.5 mg group 2.
- Gastrointestinal adverse reactions, including diarrhea, occurred more frequently in patients treated with TRULICITY compared to placebo, with 21% of patients in the placebo group, 32% in the 0.75 mg group, and 41% in the 1.5 mg group experiencing gastrointestinal adverse reactions 2.
- The severity of gastrointestinal adverse reactions, including diarrhea, was graded as mild in 58% and 48% of cases, moderate in 35% and 42% of cases, and severe in 7% and 11% of cases for the 0.75 mg and 1.5 mg groups, respectively 2.
From the Research
Dulaglutide and Diarrhea
- Dulaglutide is a once-weekly subcutaneously administered glucagon-like peptide-1 (GLP-1) receptor agonist used to treat type 2 diabetes mellitus (T2DM) 3.
- The most frequently reported adverse events in clinical trials were gastrointestinal-related, including diarrhea 3, 4, 5.
- A post hoc analysis of the AWARD-11 phase 3 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 incidence of diarrhea (≤4%) was primarily observed soon after the initiation of dulaglutide treatment at 0.75 mg 6.
- The incidence of diarrhea then declined throughout the remainder of the study, even with dose escalation to 1.5,3.0, and 4.5 mg 6.
- Most gastrointestinal adverse events, including diarrhea, were mild to moderate in severity, with severe events occurring in ≤0.6% of patients 6.
- A systematic review and meta-analysis found that dulaglutide had a statistically higher incidence of gastrointestinal adverse events, including diarrhea, compared to insulin glargine 7.
- However, dulaglutide may serve as an effective alternative to provide improvement in glycemic control with weight loss and less hypoglycemia in patients with T2DM, despite the increased risk of gastrointestinal adverse events 7.