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Hwa Jeong Seo 1 Article
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
Hwa Jeong Seo, Hyun Sook Oh
Epidemiol Health. 2021;43:e2021103.   Published online December 17, 2021
DOI: https://doi.org/10.4178/epih.e2021103
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AbstractAbstract AbstractSummary PDFSupplementary Material
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.
Summary
Korean summary
당뇨 환자는 암 발병 위험이 높으며 암은 주요 사망 원인이다. 당뇨환자의 암발생 예방을 위한 관리로서, 당뇨병 진단 후 약물 치료 시기에 대한 연구는 부족하다. 또한, 전 세계적으로 가장 흔히 처방되는 당뇨병 치료제인 메트포민은 암 예방 효과가 있다고 알려져 왔으나 관측연구에서 발생하는 선택 편향의 문제가 제기되었고, 최근 일부 연구에서 기존의 암 예방 효과와 상충되는 결과가 나오고 있어 논쟁이 이어지고 있다. 본 연구는 선택 편향을 통제한 코호트 연구에서 조기 약물 치료와 메트포민 사용이 당뇨환자의 암 예방에 효과적임을 밝혔다. 따라서 의사들은 처음 당뇨 진단을 받은 환자에게 조기에 약물 처방을 하고, 환자들은 처방에 잘 따라야 한다. 조기 처방 약물로서 메트포민이 권장된다.
Key Message
Diabetic patients have a high risk of developing cancer, and cancer is the leading cause of death. There are few studies on the timing of medication treatment after diagnosis of diabetes. In addition, metformin, the most commonly prescribed diabetes treatment worldwide, is known to have cancer-preventive effects, but the problem of selection bias that occurs in observational studies has been raised, and some studies have recently been contradicting the existing cancer-preventing effects of metformin. This study, in a cohort study controlled for selection bias, demonstrated that early medication treatment and metformin use were effective in preventing cancer in diabetic patients.

Epidemiol Health : Epidemiology and Health