From the Guidelines
Metformin is typically not given in TDS (three times daily) dosing, and the standard dosing for metformin is usually once or twice daily. The most common dosing regimens for metformin are:
- Once daily: Usually taken with the evening meal, often at 500 mg or 850 mg
- Twice daily: Usually taken with breakfast and dinner, often at 500 mg or 850 mg each time For immediate-release metformin, the maximum recommended daily dose is generally 2550 mg, divided into 2 doses, as stated in the 2009 consensus algorithm for the initiation and adjustment of therapy 1. For extended-release formulations, once-daily dosing is common, as mentioned in the 2025 standards of care in diabetes 1.
The reason for avoiding TDS dosing is to improve patient compliance and reduce gastrointestinal side effects. Metformin has a relatively long half-life, allowing for less frequent dosing. Additionally, taking the medication with meals helps to minimize gastrointestinal disturbances, which are common side effects of metformin. When initiating metformin therapy, it's usually recommended to start at a low dose and gradually increase to the target dose over several weeks to further minimize gastrointestinal side effects and improve tolerability, as suggested by the 2009 consensus algorithm 1.
According to the 2025 standards of care in diabetes, metformin is a commonly used medication that historically has been the first-line treatment for type 2 diabetes, and it is available in an immediate-release form for twice-daily dosing or as an extended-release form that can be given once daily 1. The principal side effects of metformin are gastrointestinal intolerance, which can be mitigated by gradual dose titration and/or using extended-release formulation, as mentioned in the 2025 standards of care in diabetes 1.
Therefore, the recommended dosing regimen for metformin is once or twice daily, rather than three times daily, to minimize gastrointestinal side effects and improve patient compliance, as supported by the 2009 consensus algorithm 1 and the 2025 standards of care in diabetes 1.
From the FDA Drug Label
The recommended starting dose of metformin hydrochloride tablets are 500 mg orally twice a day or 850 mg once a day, given with meals. Increase the dose in increments of 500 mg weekly or 850 mg every 2 weeks on the basis of glycemic control and tolerability, up to a maximum dose of 2550 mg per day, given in divided doses. Doses above 2000 mg may be better tolerated given 3 times a day with meals.
Metformin is not typically administered three times a day (TDS) as the standard dosing, but doses above 2000 mg may be given three times a day with meals for better tolerability 2.
From the Research
Metformin Administration Frequency
- The administration frequency of metformin can vary depending on the formulation, with immediate-release (IR) metformin typically administered twice or thrice daily, and extended-release (XR) metformin administered once daily 3, 4, 5.
- Studies have shown that metformin XR can be administered once daily, with comparable efficacy and safety to metformin IR administered twice daily 4, 5.
- One study found that patients with type 2 diabetes who had been receiving thrice-daily metformin IR achieved comparable glycemic control when therapy was switched to once- or twice-daily metformin XR at the same total daily dose 3.
- Another study compared the efficacy and safety of metformin XR and IR in patients with type 2 diabetes, and found that metformin XR demonstrated efficacy and safety similar to that of metformin IR over 24 weeks, with the advantage of once-daily dosing 5.
Specific Administration Frequencies
- Metformin IR is typically administered twice or thrice daily, with a total daily dose of 1-2 g/day 3, 6.
- Metformin XR is typically administered once daily, with a total daily dose of 1-2 g/day 4, 5.
- There is no evidence to suggest that metformin is typically administered three times a day (TDS) in clinical practice, although it may be administered thrice daily in some cases 3.