HbA1c at diagnosis may predict metformin failure, study finds

A model that included baseline HbA1c level, age, sex, and race/ethnicity had high discrimination for predicting failure risk, with the strongest association seen for HbA1c.

Patients with a high HbA1c level at diabetes diagnosis as well as other clinical factors may be less likely to benefit from first-line metformin therapy, according to a recent study.

Researchers performed a cohort study at three U.S. sites to identify demographic and clinical factors in the electronic health record (EHR) that could predict failure of metformin therapy, defined as either not meeting a target HbA1c level of less than 7% within 18 months of the index date or starting dual therapy. They used models to evaluate overall risk prediction performance and the relative contribution of individual factors when using EHR data to determine risk for metformin failure. The results were published Jan. 7 by the Journal of Clinical Endocrinology & Metabolism.

Overall, 22,047 patients (mean age, 57 years; 48% women) at sites in Arizona, Mississippi, and Minnesota who began taking metformin after at least one abnormal result on a diabetes screening test were included in the study. Seventy-six percent were non-Hispanic White, 9.7% were African American, 7% were Hispanic, 2% were Asian, and 4.4% were of other ethnicity or were multiracial. The overall rate of metformin failure was high at 33%. A model that included baseline HbA1c level, age, sex, and race/ethnicity had a high discrimination performance for metformin failure risk (C-index, 0.731; 95% CI, 0.722 to 0.740), with the strongest association for higher baseline HbA1c level dwarfing the other predictors. Model performance improved slightly when other clinical factors were added (C-index, 0.745 [95% CI, 0.737 to 0.754]; P<0.0001).

The researchers noted that their study was observational and that missing data could have led to bias. They concluded that metformin failure is common among patients beginning therapy for diabetes and that several clinical factors available in the EHR could help identify those at higher risk. “Our study results suggest increased monitoring with potentially earlier treatment intensification to achieve glycemic control may be appropriate in patients with clinical parameters described in this paper,” they wrote. “Further, these results call into question the ubiquitous use of metformin as the first line therapy and suggest a more individualized approach may be needed to optimize therapy.”