Prescription patterns and therapeutic effects of second-line drugs in Japanese patients with type 2 diabetes mellitus: Analysis of claims data for metformin and dipeptidyl peptidase-4 inhibitors as the first-line hypoglycemic agents.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP4is) and metformin are the most frequently prescribed first-line drugs for Japanese patients with type 2 diabetes (T2D). We investigated the risk of cardiovascular events by second-line treatment type in these patients. RESEARCH DESIGN AND METHODS: Patients with T2D, prescribed either metformin or DPP4i as a first-line drug, were identified in claims data from Japanese acute care hospitals. The primary and secondary outcomes were cumulative risks of MI or stroke and of death, respectively, from second-line treatment initiation. RESULTS: Patients prescribed first-line metformin or DPP4i was 16,736 and 74,464, respectively. In patients receiving first-line DPP4i, the death incidence was lower in those receiving second-line metformin than in those receiving second-line sulfonylurea (p < 0.001), whereas the primary outcome was not significantly different. No significant differences were observed for either outcome when DPP4is and metformin were used as first- and second-line drugs or vice versa. CONCLUSIONS: Metformin was suggested to have larger effect to reduce death than sulfonylurea in patients receiving first-line DPP4i. The order of first- and second-line for the DPP4i and metformin combination did not affect the outcomes. Given the nature of the study design, certain limitations, including potential under-adjustment for confounders, should be considered.

Comparison of the effects on cardiovascular events between use of metformin and dipeptidyl peptidase-4 inhibitors as the first-line hypoglycaemic agents in Japanese patients with type 2 diabetes mellitus: a claims database analysis.

OBJECTIVES: To compare the risk of cardiovascular events from the initiation of therapy between metformin and dipeptidyl peptidase-4 inhibitors (DPP-4i) as first-line therapy. DESIGN: Retrospective cohort study using two claims databases. SETTING: The MDV database (provided by Medical Data Vision) comprised data from acute care hospitals, and the JMDC database (provided by JMDC) comprised data from individuals covered by health insurance societies. PARTICIPANTS: Those who were diagnosed with type 2 diabetes at ≥18 years, prescribed metformin or DPP-4i as the first-line hypoglycaemic agent, had medical records of ≥6 months before the index prescription and had available glycated haemoglobin (HbA1c) data for the period, including the index date and 30 days before it (defined as the baseline) were included. Those diagnosed with type 1 diabetes and/or a history of myocardial infarction (MI) or cerebrovascular diseases were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcomes were cumulative risks from Kaplan-Meier curves or HRs of patients prescribed metformin compared with DPP-4i. The primary endpoint was the diagnosis of MI or stroke associated with hospitalisation. Patient demographics, prescribed drugs and laboratory test values of HbA1c and estimated glomerular filtration rate at baseline were adjusted. The study period starting from the index included treatment after initial monotherapy. RESULTS: Overall, 2089 and 6686 patients in the MDV database and 1506 and 3635 in the JMDC database were prescribed metformin and DPP-4i, respectively. The HR of the primary endpoint was 0.879 with no statistical significance (95% CI 0.534 to 1.448, p=0.613) in the MDV database, while it was significantly lower, 0.398 (95% CI 0.213 to 0.742, 0.004) in the JMDC database. CONCLUSIONS: Patients who received metformin as first-line therapy may have reduced cardiovascular events than those receiving DPP-4i. This study conforms to previous Japanese database studies, despite the consideration of its limitation being an observational design.

Comparative Effects of Metformin and Dipeptidyl Peptidase-4 Inhibitors in Japanese Obese Patients with Type 2 Diabetes: A Claims Database Study.

INTRODUCTION: Metformin has demonstrated favorable effects on glycemic control in patients with type 2 diabetes (T2D), regardless of the body mass index (BMI). On the contrary, dipeptidyl peptidase-4 inhibitors (DPP-4is) are reportedly less effective in patients having high BMI values (≥ 25 or ≥ 30). The aim of this study was to compare metformin and DPP-4is as first-line treatment for their effects on glycemic control and improvement of other health outcomes among obese and non-obese Japanese patients with T2D. METHODS: A Japanese health insurance claims database that also included annual medical checkup data was used. This database included data on company employees who were members of health insurance societies and their family members. Most patients were aged < 65 years and most were men. Inclusion criteria were: (1) a first T2D diagnosis between May 2010 and June 2017; (2) either metformin or a DPP-4i prescribed as the first-line antidiabetic therapy; and (3) glycated hemoglobin (HbA1c) and BMI data available for the 3-month period immediately preceding the initiation of antidiabetic treatment (baseline). The reduction rate in excessive HbA1c (> 6.5%; primary outcome) and changes in fasting plasma glucose, BMI, triglyceride, cholesterol, and abdominal circumference (secondary outcomes) at 12 months from baseline were compared between treatments. RESULTS: When evaluated relative to the baseline BMI, the mean reduction rate in excessive HbA1c tended to be higher in the metformin group than in the DPP-4i group, especially in patients with BMI ≥ 25. Similarly, significant improvement was observed in most outcomes in obese patients prescribed metformin compared to those prescribed a DPP-4i. In contrast, in patients with BMI < 25, HbA1c reduction was greater in patients prescribed DPP-4i and fewer outcomes showed significant improvement in patients prescribed metformin. CONCLUSION: In obese Japanese patients with T2D, greater improvements in glycemic control and other outcomes were seen with metformin as first-line treatment for T2D compared with DPP-4is, although some limitations regarding the database information should be considered.