Does metformin (Metformin) extended release (ER) cause less diarrhea?

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DS

Dainyal Siddiqui, MD

Internal Medicine

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Manuel Jimenez, MD

Cardiology

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Franz Pierre-Louis, MD

Infectious Disease

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Last updated: May 1, 2025 • View editorial policy

From the Guidelines

Metformin extended-release (ER) is likely to cause less diarrhea compared to immediate-release metformin, as the extended-release formulation reduces gastrointestinal side effects by avoiding high peak concentrations in the intestines. According to the 2025 standards of care in diabetes, metformin is a commonly used medication for type 2 diabetes, and its principal side effects include gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea 1. However, the study notes that these side effects can be mitigated by gradual dose titration and/or using the extended-release formulation.

The extended-release formulation of metformin is designed to release the medication slowly over time, which reduces the likelihood of gastrointestinal side effects like diarrhea. If a patient is experiencing diarrhea with regular metformin, switching to metformin ER might help reduce this side effect, as seen in patients who switch from immediate-release to extended-release formulations 1. Some key points to consider when using metformin ER include:

  • Taking metformin with food can further minimize gastrointestinal issues
  • Even with the ER formulation, some patients may still experience diarrhea, especially when first starting the medication or when increasing the dose
  • If diarrhea persists despite using the ER formulation, consulting a healthcare provider about adjusting the dosage or considering alternative medications is recommended

It's essential to weigh the benefits of metformin, including its effectiveness in reducing risks of microvascular complications, cardiovascular events, and death, against the potential side effects, and to consider the extended-release formulation as a way to minimize gastrointestinal intolerance 1.

From the Research

Metformin ER and Diarrhea

  • Metformin ER (extended-release) may cause less diarrhea compared to immediate-release metformin, as suggested by a retrospective cohort study 2.
  • The study found that patients switched from immediate-release metformin to metformin ER experienced fewer gastrointestinal side effects, including diarrhea, on comparable doses of the extended-release metformin 2.
  • Another study also noted that extended-release metformin improves gastrointestinal tolerability and allows once-daily dosing, which may lead to better adherence and reduced side effects such as diarrhea 3.
  • However, it is essential to note that the frequency of individual gastrointestinal adverse events, including diarrhea, did not differ significantly between metformin ER and immediate-release metformin cohorts in the retrospective chart review 2.

Gastrointestinal Tolerability

  • Extended-release metformin is generally considered to be better tolerated than immediate-release metformin, with a lower incidence of gastrointestinal side effects such as diarrhea 3.
  • A study found that maximum plasma metformin concentrations are reached more slowly with the extended-release formulation, which may contribute to improved gastrointestinal tolerability 3.
  • Patients with a history of gastrointestinal adverse events while taking immediate-release metformin may still experience fewer side effects when switched to metformin ER 2.

Clinical Implications

  • The use of metformin ER may be beneficial for patients with type 2 diabetes who experience gastrointestinal side effects, including diarrhea, while taking immediate-release metformin 2, 3.
  • Clinicians should consider the potential benefits of metformin ER in improving gastrointestinal tolerability and reducing side effects such as diarrhea when prescribing metformin to patients with type 2 diabetes 3.

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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