Metformin and kidney function: at what GFR to stop or reduce the dose?
Metformin in reduced kidney function: maximum daily dose per GFR band from the EU product information, contraindication below 30 mL/min, monitoring, contrast and surgery.
By Medelix EditorialPublished: 3 min read
"At what GFR should metformin be stopped?" is one of the most common kidney-function questions. The short answer: below a GFR of 30 mL/min metformin is contraindicated. Between 30 and 59 mL/min it can be continued, with a lower maximum dose. These rules have applied across the EU since a European Medicines Agency (EMA) referral in 2016 [1].
Key points
- GFR < 30 mL/min: metformin is contraindicated [1, 2].
- GFR 30–59 mL/min: use is possible with a reduced maximum dose; the starting dose is at most half of the maximum dose [1, 2].
- Monitoring: GFR before starting and at least annually thereafter; more often, e.g. every 3–6 months, in people at risk of progression and in older people [1, 2].
- Pause: in conditions that can acutely worsen kidney function, before iodinated contrast, and for surgery under general, spinal or epidural anaesthesia [2].
Calculate directly: eGFR calculator (CKD-EPI), eGFR by EKFC and Cockcroft-Gault creatinine clearance.
Maximum dose per GFR band
Since 2016, the product information of metformin medicines in the EU contains a dosing table by GFR [2]:
| GFR (mL/min) | Total maximum daily dose (divided into 2–3 doses) | Notes from the product information |
|---|---|---|
| 60–89 | 3,000 mg | Consider dose reduction as kidney function declines |
| 45–59 | 2,000 mg | Review lactic-acidosis risk factors before starting; starting dose at most half of the maximum |
| 30–44 | 1,000 mg | as for 45–59 |
| < 30 | – | contraindicated |
The 60–89 mL/min maximum is not identical in every product information: products whose general maximum is lower (some prolonged-release forms, for example) list a lower figure. The product information of the prescribed medicine always takes precedence.
Why the limit is 30 mL/min
Metformin is excreted unchanged by the kidneys. When kidney function falls, plasma concentrations rise, and with them the risk of lactic acidosis, a rare but life-threatening complication [2]. Before 2016 many product informations already contraindicated metformin below a creatinine clearance of 60 mL/min. After reviewing the data, the EMA concluded that patients with moderately reduced kidney function (GFR 30–59 mL/min) can use metformin at adjusted doses; the contraindication below 30 mL/min remained [1].
The KDIGO guideline on diabetes in chronic kidney disease likewise recommends metformin for people with type 2 diabetes and an eGFR of 30 mL/min/1.73 m² or more, with dose adjustment as eGFR falls [3].
When metformin must be paused
The product information lists situations in which metformin is temporarily stopped [2]:
- Acute conditions that can worsen kidney function, such as dehydration (vomiting, diarrhoea, fever), severe infection or shock.
- Iodinated contrast: stop before or at the time of the procedure and restart no earlier than 48 hours afterwards, once kidney function has been re-checked and is stable.
- Surgery under general, spinal or epidural anaesthesia: stop at the time of surgery; restart no earlier than 48 hours after surgery or after oral nutrition has resumed, provided kidney function is stable.
Which GFR is meant?
The product information refers to GFR. In practice the lab report usually shows eGFR by CKD-EPI, indexed to 1.73 m² body surface area. In very small or very large people the non-indexed GFR can differ considerably, and the product information of some other medicines specifies Cockcroft-Gault creatinine clearance instead. Our article Interpreting eGFR explains how the equations differ.
Checklist
- Measure GFR before starting; no metformin below 30 mL/min.
- At 30–59 mL/min: maximum dose per the table, starting dose at most half of it.
- Re-check at least annually, every 3–6 months in older people and those at risk of progression.
- Pause during acute illness with dehydration, before contrast and before surgery.
- When in doubt, read the product information of the specific medicine.
This article describes the authorised conditions of use. It replaces neither the product information nor the clinical decision for an individual patient.
Sources
- European Medicines Agency. Metformin and metformin-containing medicines – Article 31 referral. CHMP opinion of 13 October 2016, Commission decision of 12 December 2016. ema.europa.eu
- Summary of Product Characteristics of metformin-containing medicines, sections 4.2, 4.3 and 4.4, e.g. Metformin 500 mg tablets. medicines.org.uk
- Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022;102(5S):S1–S127. doi:10.1016/j.kint.2022.06.008