How to explain to a patient that metformin (a biguanide oral hypoglycemic agent) is being excreted unchanged in her stool?

From the Guidelines

The patient should be reassured that the metformin is still working effectively, even if they see what appears to be the medication in their stool, as the active ingredient is absorbed in the digestive tract while the inert shell is eliminated. This is a common occurrence with extended-release formulations, such as metformin, which are designed to slowly release the medication throughout the day 1. The outer shell of the tablet is not absorbed and is passed through the digestive system, which can be mistaken for the medication itself not being absorbed. However, the active medication is absorbed in the digestive tract, allowing it to work continuously to help control blood sugar levels over a longer period.

The benefits of extended-release metformin include fewer pills and more consistent blood sugar control, which is crucial for managing type 2 diabetes and reducing the risk of microvascular complications, cardiovascular events, and death 1. If the patient remains concerned, they could be advised to speak with their pharmacist about switching to immediate-release metformin tablets, which dissolve completely, though these typically need to be taken multiple times per day rather than once daily. Some key points to consider when discussing metformin with the patient include:

• The medication is effective and safe, and reduces risks of microvascular complications, cardiovascular events, and death 1
• The principal side effects of metformin are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea, which can be mitigated by gradual dose titration and/or using extended-release formulation 1
• Metformin may be safely used in people with estimated glomerular filtration rate ≥30 mL/min/1.73 m², but very high circulating levels have been associated with lactic acidosis, although this is very rare 1.

From the FDA Drug Label

Metformin is negligibly bound to plasma proteins. Metformin partitions into erythrocytes, most likely as a function of time Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours.

The patient is seeing metformin in her stool because approximately 40-50% of the drug is not absorbed from the gastrointestinal tract, as indicated by the absolute bioavailability of 50% to 60%. This unabsorbed portion of the drug is then excreted in the feces. It is essential to explain to the patient that this does not affect the efficacy of the medication, as the absorbed portion is still effective in lowering blood glucose levels. The patient should be reassured that this is a normal phenomenon and not a cause for concern 2.

• Key points to emphasize:
  • The drug is not being absorbed completely, which is normal
  • The unabsorbed portion is excreted in the stool
  • The absorbed portion is still effective in lowering blood glucose levels
  • This does not affect the efficacy of the medication

From the Research

Explaining Long-Acting Metformin to a Patient

• Metformin is a commonly used medication for managing type 2 diabetes, and it works by reducing glucose production in the liver, decreasing insulin resistance, and increasing insulin sensitivity 3.
• When explaining long-acting metformin to a patient, it's essential to discuss how the medication is absorbed and utilized by the body.
• The patient's concern about seeing metformin in their stool can be addressed by explaining that metformin is not completely absorbed by the body and a significant portion of it is excreted in the feces 3.
• It's crucial to reassure the patient that this does not affect the medication's efficacy in managing their diabetes.

Mechanism of Action and Efficacy

• Metformin has been shown to be effective in lowering blood glucose levels without increasing the risk of hypoglycemia 3, 4.
• The medication has been used for the treatment of obesity, gestational diabetes, and polycystic ovary syndrome, in addition to type 2 diabetes 3.
• Studies have demonstrated that metformin can be used as a first-line agent in the management of diabetes, although newer agents may be preferred in certain cases 3, 5, 6.

Adherence and Patient Education

• Long-term metformin adherence is crucial for effective diabetes management, and predictors of adherence include early adherence, lower depression scores, and planned strategies to improve adherence 7.
• Patient education and counseling can play a significant role in promoting adherence and supporting patients in managing their diabetes 7.
• By addressing the patient's concerns and providing clear explanations about metformin, healthcare providers can help improve adherence and overall diabetes management.