Is It the Right Time to Deprescribe This Frail Patient's Metformin?

Charles P. Vega, MD


May 20, 2021

My Take: Option 1, With Caveats

This is one of those fun multiple-choice questions in which a valid argument could be made for any of the options. I will choose option 1: Discontinue metformin now and monitor the patient's glycemic control.

Recommendations for the management of type 2 diabetes among older and/or more frail adults have changed in recent years, with an emphasis on patient safety and avoiding hypoglycemia. A goal A1c of < 8% is reasonable among persons with multiple comorbidities and reduced life expectancy.

But a closer look at the latest guidelines from the American Diabetes Association regarding A1c targets reveals highly pertinent information for the present case. Long-standing vs recently diagnosed type 2 diabetes should merit consideration for a less stringent A1c goal. Given the more limited benefit of intensive glycemic control on macro- vs microvascular outcomes of diabetes as well as the risk for medication adverse effects, the presence of established vascular complications also argues for a higher A1c target.

Prevention of adverse events such as hypoglycemia is of paramount importance for this patient, but as a master clinician, you have already purged her drug list of sulfonylureas and insulin. She is left only with good-old metformin. But is it helping her?

Moderate-quality evidence from retrospective cohort studies would suggest that the answer is yes. In one study focused on patients with type 2 diabetes and a history of cardiovascular disease, the use of metformin was associated with an adjusted hazard ratio for mortality of 0.76 (95% CI, 0.65-0.89). While this difference in mortality was maintained in the broad population of patients at age 65 years or older, it was not significant in an analysis limited to persons at age 80 years or more.

This finding in part explains a recommendation from a more recent meta-analysis that the discontinuation of metformin should be considered among patients at age 80 years and older, or among those with an eGFR < 60 mL/min. This latter recommendation is contradicted by data which demonstrate that metformin may improve rates of cardiovascular events and all-cause mortality among patients with stage 3 chronic kidney disease.

Would discontinuation of metformin allow the patient to stay in her target A1c range? Metformin lowers A1c by about 1%. Therefore, this patient's A1c would rise from 7.5% to approximately 8.5% following discontinuation of metformin. To me, that value would be right at the acceptable maximum A1c for this patient.

Deleting metformin and replacing it with an SGLT2 inhibitor is possible in this case. That medication class is not associated with a risk for hypoglycemia and has been demonstrated to have beneficial effects on renal and cardiovascular outcomes. However, the mean age of participants in the major cardiovascular outcomes trials of SGLT2 inhibitors was less than 65 years. SGLT2 inhibitors do seem effective in the subgroup of patients over the age of 65 years, but there are fewer data for individuals older than 80 years.

Personally, I would continue the metformin except for one major concern for this patient's ongoing health: the presence of Alzheimer's disease and the level of support she receives in managing a complex medication regimen. Simplifying her medication regimen is a priority for this patient, and some difficult choices can be anticipated as her dementia progresses and the risks for medication misuse and adverse events increase. The decision to discontinue metformin should not be taken lightly, but I think that it is in the best interest of the patient and family at this time. Regarding her diabetes control, I believe that this patient has already suffered the majority of complications associated with hyperglycemia, and I would monitor her appetite and diet closely. Appetite often declines as dementia progresses, resulting in lower blood glucose levels.

My conclusion for this patient is that the potential benefit of metformin is now outweighed by the risk for harm, either through adverse events related to metformin or the more global burden of a complicated medication regimen. What do you think? Please share your comments on this interesting and fairly common issue in primary care.


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