By Dr. Geoffrey Modest
The FDA is revising its warnings about the risks of metformin in those with chronic kidney disease (CKD) — See http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm494829.htm , or http://www.fda.gov/downloads/Drugs/DrugSafety/UCM494140.pdf for more info), “Requiring manufacturers to revise labeling of metformin-containing drugs to indicate that these products may be safely used in patients with mild to moderate renal impairment”. Although I have sent out many blogs on metformin, I think it is such an important drug that I am sending out this as yet another one. The new FDA labeling recommendations:
- Before starting metformin, check eGFR
- Metformin is contraindicated in patients with an eGFR <30
- Starting metformin in those with eGFR 30-45 is NOT recommended
- Obtain eGFR at least annually, more frequently if increased risk of renal dysfunction (e.g., elderly)
- If a patient is on metformin and the eGFR falls to below 45, assess the benefits and risks of continuing treatment [not further defined…]. Discontinue metformin if eGFR falls to <30
- Discontinue metformin at time, or before, an iodinated contrast imaging procedure in patients with eGFR 30-60, in those with a history of liver disease, alcoholism, or heart failure; and in those getting intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the procedure and restart metformin if renal function is stable.
So, a few comments:
- It’s about time….. See a few of my many blogs below on metformin, which highlight its incredible importance in diabetics, its current use in the US in those with CKD despite prior strict precautions, its general use in Europe where regulatory agencies suggest using it with decreasing doses depending on the degree of CKD, and even a blog which refers to its effects on the microbiome (and suggesting that these effects may be extremely important in metformin’s mechanism of action).
- One concern with the above is that they suggest following eGFR more closely in the elderly. This is difficult, since (at least in our lab), eGFR is not reported in those >70: “eGFR values may not be accurate on patients greater than 70 years of age and are not calculated”. My approach is to continue with metformin in the elderly (even those in their 90s) if their creatinine seems “reasonable” — not easy to quantitate, but if their creatinine is below 1.5 or so, and throwing in some gestalt about their likely muscle mass… But, bottom line, I have been doing this for years on a pretty large patient base and without any adverse effects. Though I often only use 500 mg/d (occasionally 250 mg/d), I find patients still get a huge effect from the med. And, by the way, given some issues with metformin tolerance (mostly GI), I often leave younger people on 500 mg once or twice a day, with really good effect (i.e., I rarely crank it up to the 1000 bid dosage, since my sense from the not-so-great literature, and my experience, is that 500-1000 mg total per day gives about 75-85% of the efficacy of the maximal dose)
https://stg-blogs.bmj.com/bmjebmspotlight/2015/07/23/primary-care-corner-with-geoffrey-modest-md-metformin-ckd-and-death/ which looked at 813 metformin users with severe CKD (creatinine >6 mg/dL) who did NOT have increased mortality if the dose of metformin was low (<= 500 mg/d)
https://stg-blogs.bmj.com/bmjebmspotlight/2015/01/23/primary-care-corner-with-geoffrey-modest-md-metformin-in-renal-failure/ is a more systematic review of metformin use in those with less severe CKD, suggesting an algorithm for metformin dose adjustment
https://stg-blogs.bmj.com/bmjebmspotlight/2015/01/28/primary-care-corner-with-geoffrey-modest-md-heart-failure-microbiome/ looked at the effect of red meat on the microbiome (increasing TMAO levels, which are strongly pro-atherogenic) and also highlighting that metformin induces positive changes in the microbiome which decrease insulin resistance