Comparative Effectiveness of Metformin Dosage Uptitration Versus Adding Another Antihyperglycemic Medication on Glycemic Control in Type 2 Diabetes Patients Failing Initial Metformin Monotherapy: A Retrospective Cohort Study.

Metformin is recommended as first-line treatment for type 2 diabetes (T2D). A disadvantage of metformin is the possibility of gastrointestinal adverse effects in some patients. Many T2D patients are not able to achieve/maintain glycemic control from initial metformin treatment and receive treatment intensification by means of metformin dosage uptitration or addition of a T2D drug. This retrospective study evaluated the comparative effectiveness of these 2 treatment intensification strategies. The study cohort included T2D patients at a US integrated health care system who: were initiated on metformin monotherapy (MM) during January 2009 - September 2013; had an uncontrolled HbA1c (≥7%) after at least 90 days of MM; and received metformin dosage uptitration or an additional T2D medication within 6 months of the uncontrolled HbA1c reading. Statistical techniques included Kaplan-Meier curves and Cox proportional hazards regression. The study cohort included 1167 patients, 52.4% male and 65.1% white, with a mean age of 55.3 (±11.9) years. Of these, 49.1% received metformin dosage uptitration and 50.9% received an additional T2D medication. Metformin dosage uptitration was as effective as adding another T2D medication with the probability of not achieving glycemic control (P = 0.599) and rate of glycemic control (adjusted hazard ratio = 1.28, 95% confidence interval = 0.98-1.68) within 6 months of intensification not significantly different between the 2 groups. Metformin dosage uptitration could be a preferable initial intensification strategy in patients failing initial MM unless there is a concern for gastrointestinal adverse effects, in which case adding a T2D medication might be preferable.