Clinical guidelines recommend metformin monotherapy (MM) as an initial glucose-lowering therapy for type 2 diabetes (T2D) patients [pts]. While studies have previously reported the incidence of metformin monotherapy failure, there are limited data specifically assessing the rate of “secondary” MM failure (defined as loss of control following initial achievement of glycemic control). The current study sought to characterize and evaluate factors associated with secondary failure among T2D pts on MM in a diverse U.S. population. Using the GE Centricity Electronic Medical Record database, we conducted a retrospective study of T2D pts ≥18 years initiating MM between 1/2013-5/2016 and achieving an HbA1c <7% (index date) within 6 months of initiation. Secondary MM failure was assessed at 6, 12, 18, and 24 months after index date and was defined based on HbA1c ≥7% or by treatment change (therapy switch or add-on intensification). Multivariable logistic regression was used to evaluate the factors associated with secondary MM failure. Of 4,775 pts included, 53.4% were female, the median age was 63 years and median HbA1c at index date was 6.4%. At 6 months, the proportion of pts who experienced MM failure by HbA1c ≥7% was 9.76% and by treatment change was 6.01%. At 12, 18 and 24 months, these proportions (%) were 16.20/8.00, 22.95/9.36, and 28.82/10.68, respectively. Factors positively associated with secondary MM failure (HbA1c ≥7%) at 24 months were male gender, HbA1c at index date and younger age (<65 years). These data suggest that after initially achieving an A1C <7%, a substantial proportion of pts on MM experience secondary failure within a relatively short period of time, with an increasing number experiencing failure within 2 years. Pts controlled on MM may benefit from regular HbA1c testing to ensure timely treatment modification. Further studies assessing whether initial metformin combination therapy would result in more durable glycemic control would also be of value.


T. Weiss: Employee; Self; Merck & Co., Inc. K. Iglay: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. P. Verma: None. S. Rajpathak: None. L. Yang: Employee; Self; Bristol-Myers Squibb Company, Merck & Co., Inc. L. Blonde: Consultant; Self; Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi US. Research Support; Self; Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi US. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US.

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