Effects of early medication treatment and metformin use for cancer prevention in diabetes patients: a nationwide sample cohort study in Korea using extended landmark time analysis

Abstract

Objectives: This study investigated the effectiveness of early medication treatment and metformin use for cancer prevention in type 2 diabetes patients.

Methods: Population-based cohort data were used from the Korean National Health Insurance Service-National Sample Cohort database (KNHIS-NSC) for 2002-2013. Patient-specific medication prescription status was defined by the landmark time (LMT; a fixed time after cohort entry), considering both pre- and post-LMT prescriptions to control methodological biases in observational research. The LMT was set to 2 years. Logistic regression analysis with multivariable adjustment was conducted to analyze cancer incidence by patient-specific medication prescription status.

Results: Only 33.4% of the subjects were prescribed medication early (before the LMT) with compliance. Cancer incidence in individuals with early prescription and compliance was 25% lower (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.67 to 0.84) than in those without. As early-prescribed medications, metformin monotherapy and metformin combination therapy were associated with 34% (OR, 0.66; 95% CI, 0.51 to 0.83) and 25% (OR, 0.75; 95% CI, 0.64 to 0.88) lower cancer risk than non-use, respectively. Patients who were prescribed late (post-LMT) but did not comply with the prescription had a 24% (OR, 1.24; 95% CI, 0.97 to 1.58) higher cancer incidence than non-users. Among patients who started monotherapy early without changes throughout the entire follow-up period, those who started on metformin had a 37% (OR, 0.63; 95% CI, 0.41 to 0.99) lower risk of cancer than non-metformin users.

Conclusions: Doctors must prescribe antidiabetic medication early, and patient compliance is required, regardless of the prescription time, to prevent cancer. Metformin monotherapy or combination therapy is recommended as an early prescription.

Keywords: Anticancer agents; Drug prescription; Medication compliance; Metformin; Type 2 diabetes mellitus.

Figure 1

Flowchart of the sampling procedure.

Figure 2

Medication prescription status; (A) early prescription with compliance, (B) early prescription with poor compliance, (C) late prescription with compliance, (D) late prescription with poor compliance, and (E) no prescription ever. TPD, total prescription days; LMT, landmark time.