Does metformin cause changes in bowel habits, including diarrhea?

Metformin and Bowel Changes

Yes, metformin commonly causes diarrhea and changes in bowel habits, occurring in approximately 53% of patients—making it the most frequent side effect of this medication. 1

Gastrointestinal Side Effects Profile

The FDA drug label clearly documents that diarrhea is the predominant adverse reaction with metformin:

• Diarrhea occurs in 53% of metformin-treated patients compared to only 12% with placebo, representing a more than 4-fold increase 1
• Nausea and vomiting affect 26% of patients (versus 8% with placebo) 1
• Additional GI symptoms include flatulence (12%), abdominal discomfort (6%), and indigestion (7%) 1
• The American Diabetes Association confirms these gastrointestinal effects are due to bloating, abdominal discomfort, and diarrhea 2

Timing and Duration of Symptoms

Diarrhea can occur at any point during metformin therapy, not just at initiation:

• While GI side effects typically begin early in treatment, late-onset chronic diarrhea can develop after years of stable metformin use 3, 4
• One case report documented explosive watery diarrhea with occasional incontinence occurring after several years of stable therapy 3
• Another patient experienced chronic diarrhea for six years that was misdiagnosed as irritable bowel syndrome before metformin was identified as the cause 4
• Most early-onset GI symptoms generally resolve within days to weeks of continued use 1

Clinical Significance and Severity

The diarrhea can range from mild to severe enough to cause medication discontinuation:

• Diarrhea led to discontinuation of metformin in 6% of patients in clinical trials 1
• In Japanese patients, diarrhea occurred in 26.7% but was mild in most cases and disappeared within 3 days 5
• Severe cases can involve explosive watery diarrhea with incontinence 3

Risk Factors for GI Side Effects

Six specific risk factors increase the likelihood of developing diarrhea:

• Initial dose of 750 mg (versus 500 mg) 5
• Female sex 5
• Age ≤65 years 5
• Body mass index ≥25 kg/m² 5
• Aspartate aminotransferase ≥30 IU/L 5
• Alkaline phosphatase ≥270 IU/L 5
• The incidence of diarrhea increases linearly as the number of these risk factors accumulates 5

Management Strategies

Start with gradual dose titration and consider extended-release formulations:

• Begin with low doses and titrate slowly to mitigate GI intolerance 2, 6
• Take medication with meals to reduce side effects 1
• Extended-release metformin significantly reduces GI side effects: In patients switched from immediate-release to extended-release formulations, GI adverse events decreased from 26.34% to 11.71% (p=0.0006), and diarrhea specifically dropped from 18.05% to 8.29% (p=0.0084) 7
• If side effects persist beyond a few weeks, worsen, or return after resolution, consider dose reduction or temporary discontinuation 1

Diagnostic Considerations

Before pursuing extensive workup for chronic diarrhea in metformin users, trial a drug-free interval:

• Metformin-induced diarrhea is clinically similar to diabetic diarrhea but is far more common in type 2 diabetes patients 3
• Patients deserve a trial off metformin before undergoing expensive and uncomfortable diagnostic tests, even when the dosage has been stable for years 3
• Complete resolution of symptoms upon metformin discontinuation confirms the diagnosis 3, 4

Important Caveat

You may occasionally pass a soft mass in stools that looks like the metformin tablet—this is not harmful and represents the inert tablet matrix after drug absorption 1