Study: Metformin Effective for Many Patients With T2D, Chronic Kidney Disease

Some consider patients with type 2 diabetes (T2D) and chronic kidney disease poor candidates for metformin monotherapy due to the risk of lactic acidosis. However, new research finds patients who can tolerate the drug can gain similar benefits with or without kidney disease.

A new study suggests metformin is a suitable treatment option for many patients with type 2 diabetes (T2D), even if they have mild or moderate chronic kidney disease (CKD).

Metformin is generally the preferred first-line therapy for patients with T2D; however, the medication comes with a risk of lactic acidosis, a problem that is more acute in patients with CKD, since the medication is primarily cleared by the kidneys. As a result, prescriptions of metformin in patients with kidney disease have been limited, as has scholarly research into metformin’s use in these patients.

In a new report in Diabetes, Obesity and Metabolism, corresponding author Elvira O. Gosmanova, MD, of Albany Medical College, and colleagues, explained that some of the limited evidence available has suggested that metformin can be safe, even in patients with CKD, and that such patients can even see benefits such as lower mortality and lower risk of cardiovascular events.

In hopes of better understanding the risks and benefits of metformin to patients with kidney disease, Gosmanova and colleagues decided to probe a Department of Veterans Affairs database to identify patients with T2D and estimated glomerular filtration rates (eGFR) of at least 30 mL/min/1.73 m2. eGFR scores between 30 and 59 mL/min/1.73 m2 qualify a patient as having stage 3 CKD (CKD3). The search produced 145,980 patients who sought care between November 1999 and July 2017. Of those, the average age was 60.7 years, 95.3% were male, 76.5% were white, and 9% had CKD3.

The investigators sought to find out whether patients with CKD3 had significantly different experiences and significantly different changes in glycated hemoglobin (HbA1c) compared with controls.

The results showed patients with CKD3 had a higher risk of discontinuing metformin (hazard ratio [HR] 1.22; 95% CI, 1.19-1.26) or adding a second hypoglycemic agent (HR, 1.26; 95% CI, 1.13-1.40). Yet, among patients who stayed on metformin monotherapy, the benefits in terms of average HbA1c were the same for patients with CKD3 compared with those without from baseline to 12 months or 24 months.

Gosmanova and colleagues noted that, while rates of discontinuation were higher in patients with CKD3, they were not able to evaluate the reasons for discontinuation, which could be related to tolerance or other factors.

“It might also be possible that in individuals with CKD3 metformin was deliberately discontinued by providers due to a lack of glycaemic efficacy,” they wrote. “The rate of addition of second hypoglycemic agents in CKD3 patients was higher compared with non-CKD T2D patients; however, HbA1c at time of second hypoglycemic agent addition was not different between the study groups.”

Still, they said the fact that patients who were able to stay on metformin had similar success regardless of kidney disease implies that patients who can tolerate the therapy could consider the drug even if they have mild or moderate kidney disease.

“These results suggest that metformin monotherapy initiation to improve glycemic control in CKD3 is feasible; however, these patients may require closer follow-up to monitor for metformin adherence, side effects, and therapeutic efficacy,” they wrote.

The authors said further study should examine why metformin monotherapy failed in CKD3, which could help give clinicians better guidance of how to approach these patients.


Gosmanov AR, Gemoets DE, Kaminsky LS, Kovesdy CP, Gosmanova EO. Efficacy of metformin monotherapy in US veterans with type 2 diabetes and preexisting chronic kidney disease stage 3 Diabetes Obes Metab. Published online April 28, 2021. doi:10.1111/dom.14414

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