From the Guidelines
Metformin XR (extended-release) is the enteric coated, delayed release formulation of metformin (Glucophage). This formulation is designed to be taken once daily, typically with the evening meal, at doses ranging from 500 mg to 2000 mg per day. The enteric coating allows the medication to pass through the stomach intact and dissolve in the intestines, providing a gradual release of the active ingredient over time. This slower release mechanism helps reduce gastrointestinal side effects commonly associated with immediate-release metformin, such as nausea, diarrhea, and abdominal discomfort, as noted in the 2025 standards of care in diabetes 1. The XR formulation also improves patient adherence due to its once-daily dosing schedule compared to the immediate-release version which typically requires twice or three times daily dosing. Metformin XR works by the same mechanism as regular metformin - reducing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity - but with the advantage of more consistent blood levels throughout the day due to its controlled release properties. Patients should swallow the tablets whole and not crush or chew them, as this would destroy the delayed-release mechanism and potentially cause side effects.
Some key points to consider when prescribing metformin XR include:
- Monitoring for vitamin B12 deficiency, as metformin use is associated with an increased risk of deficiency 1
- Gradually increasing the daily dose to minimize gastrointestinal side effects
- Using the medication with caution in patients with hypoperfusion, hypoxemia, impaired hepatic function, or heart failure due to the increased risk of lactic acidosis 1
- Temporarily discontinuing metformin before procedures including imaging studies using iodinated contrast, during hospitalizations, and when acute illness may compromise renal or liver function 1
Overall, metformin XR is a safe and effective treatment option for patients with type 2 diabetes, and its enteric coated, delayed release formulation can help reduce gastrointestinal side effects and improve patient adherence.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Enteric Coated Metformin Formulations
- The enteric coated (delayed release) formulation of metformin is also known as extended-release metformin, which includes formulations such as Glucophage XR 2, Glumetza 3, 4, and metformin extended release 5, 6.
- These formulations are designed to provide a slower release of metformin, reducing gastrointestinal side effects and allowing for once-daily dosing.
- Examples of extended-release metformin formulations include:
- Glucophage XR: a once-daily tablet using the patented GelShield Diffusion System release mechanism 2.
- Glumetza: a proprietary once-a-day formulation of metformin hydrochloride developed by Depomed, available in 500mg and 1000mg doses 3, 4.
- Metformin extended release: available in multiple branded and generic formulations, including a 1500mg/day dose 6.
Characteristics of Enteric Coated Metformin
- Extended-release metformin formulations have similar bioavailability to conventional immediate-release formulations 6.
- They provide effective glycemic control with once-daily dosing, and are well tolerated with no increase in adverse events at higher doses 5, 6.
- These formulations may improve patient adherence due to a simpler dosing regimen and increased tolerability 5.