Sex Disparities in Treatment Patterns After Metformin Initiation Among Patients with Type 2 Diabetes Mellitus

Background: Although guidelines for diabetes recommend the same stepwise treatment for men and women, some disparities in prescribed medication have been observed. This study aims to assess sex differences among type 2 diabetes mellitus (T2D) patients in treatment transitions after metformin initiation, and HbA1c level at treatment initiation and intensification.

Methods: A cohort study was conducted using the Groningen Initiative to ANalyze Type 2 diabetes Treatment (GIANTT) database which contains electronic medical records from a dynamic cohort of T2D patients from the north of the Netherlands. Patients aged ≥18 years who initiated metformin in the period 2004-2012, and had follow-up data of 2-5 years were included. Markov modeling was conducted to estimate treatment transition rates. Transitions included dose changes, switching, discontinuation, addition of another oral hypoglycemic agent (OHA) to metformin, or initiation of insulin. Adjusted hazard ratios (aHR) for all transition rates were calculated, including sex, age and Hba1c level at baseline as covariates. HbA1c levels at initiation and intensification were compared between the sexes using Mann-Whitney U tests.

Results: In total, 12,672 metformin initiators were identified (50.4% women). The most common transition after metformin initiation was a dose increase in both sexes (probability women 0.52, men 0.59: aHR 0.94; 95%CI 0.88-1.00). After having metformin discontinued, most of the patients reinitiated metformin (probability women: 0.81, men 0.84; aHR 0.94; 95%CI 0.83-1.08). Women were more likely switch to another OHA after metformin initiation than men (aHR: 1.70; 95%CI 1.34-2.15). Men had slightly higher HbA1c levels than women at metformin initiation (mean HbA1c 7.3% vs 7.2%, p<0.001) and treatment intensification (7.7% vs 7.5%, p<0.001).

Conclusions: Sex disparities were observed in the treatment transitions among T2D patients after metformin initiation. Women more often switch metformin to other OHA, which suggests they have more tolerance problems for metformin than men. Men initiate and intensify treatment on higher HbA1c levels, indicative of less timely treatment.