Discontinuing Metformin: The Crowdsourced View

Charles P. Vega, MD

Disclosures

June 23, 2021

Recently I posed a question about a patient, drawn from my own practice: Is It the Right Time to Deprescribe This Frail Patient's Metformin?

My patient was an 81-year-old woman with type 2 diabetes of 20 years' duration, chronic kidney disease, obesity, and mild dementia. Her family hoped to reduce the number of medications she was taking, one of which was metformin. I decided that we could accept a less stringent A1c goal, so I discontinued her metformin and monitored her glycemic control.

Readers Weigh In

Thank you for the lively discussion and strong ideas regarding the care of this patient. In a case without a clear correct response to the options (continue metformin, discontinue metformin, reduce the dose, or switch to an SGLT2 inhibitor), readers' opinions were decidedly split on the best course of action.

The most common solution was a compromise: Continue metformin, but with the once-daily, extended-release form. This would reduce her pill count and the burden on the patient and her family for medication adherence. Some evidence suggests that this intervention can be effective. In a meta-analysis of 51 studies, there was a gradual reduction in medication use with each additional daily dose. The difference in medication use comparing once-daily and twice-daily regimens was -6.7%. This result was statistically significant but not highly impactful clinically. However, there was a 13.1% difference favoring once-daily dosing vs twice-daily dosing in terms of overall regimen adherence.

Another lesson I take from the advice to reduce her dosing frequency is to think outside the managed care formulary. Our managed care plans for Medicaid and Medicare do not cover extended-release metformin, so I did not even consider this option.

Metformin and the Fountain of Youth

A couple of readers mentioned another possible reason to continue metformin for this patient: as a potential anti-aging medication. There is evidence that metformin has activity on the 5'-AMP-activated protein kinase pathway, where it can help reduce inflammation and cellular stress. Metformin supplementation in middle-aged mice was associated with a 5.8% increase in lifespan. The UK Prospective Diabetes Study found a cardiovascular benefit associated with long-term metformin use among adults with diabetes, but meta-analyses have failed to find a benefit associated with cancer for metformin. Overall, there is not enough current evidence to recommend metformin as an anti-aging medicine, but two trials are underway evaluating the effects of metformin among adults without diabetes.

Thoughtful Deprescribing

Finally, it is worth considering the point of deprescribing. Patients should not feel abandoned or that they are not worthy of certain treatments. The values and preferences of patients and their supporters are highly important in the decision to discontinue chronic medications. But it is the clinician's duty to bear these things in mind:

  • Polypharmacy is common among older adults, and it is associated with a higher risk for gait decline and falls. This is true even after adjusting for confounding by indication.

  • There are many chronic medications which are unproven among older adults. More research is necessary in this area, particularly as the population as a whole ages.

There was more than one correct answer to this clinical scenario. However, a dogmatic approach that is not patient- (and family-) centered can do more than damage the relationship between clinician and patient. It can result in more loss to follow-up, less preventive care, and higher rates of morbidity and mortality.

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