Aims: To assess the development of treatment failure in Chinese patients with type 2 diabetes mellitus (T2DM) initiated on metformin or sulphonylurea (SU) monotherapy, with consideration of various potential sources of biases.
Methods: A 1:1-matched new metformin and SU user cohort on immortal time and mean propensity score after multiple imputation was selected from a cohort of 5889 Chinese patients with T2DM. Treatment failure was defined as progression to (i) combination oral anti-hyperglycemia drug therapy, (ii) insulin use, or (iii) a treatment haemoglobin A1c (HbA1c) >7.5% (58 mmol/mol). Stratified Cox regression analysis on the matched pairs was employed to examine the associations between initial monotherapy and onset of treatment failure.
Results: Of 554 new metformin and 840 new SU users, 380 were matched. During a median follow-up duration of 3 years, 173 (45.6%) metformin users and 220 (57.9%) SU users experienced treatment failure (annual failure rates of 15% and 19%, respectively). The median time from monotherapy starting to treatment failure was 3.0 [inter-quartile range (IQR): 1.8-5.4] years for metformin users, versus 1.8 (IQR: 0.9-4.1) years for SU users (p<0.001). Stratified Cox regression analysis showed significantly lower risk of treatment failure for metformin users (HR [95% CI], 0.62[0.47-0.81]; p<0.001). Consistent results were found in analyses based on traditional adjustment schemes with or without imputation.
Conclusions: By systematically incorporating new-user design, multiple imputation and matching methods, we found that Chinese patients with T2DM initiated on metformin monotherapy were associated with a significant delay in the onset of treatment failure compared to SU monotherapy.
Keywords: Diabetes; Drug use bias; Metformin; Sulphonylurea; Treatment failure.
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