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당뇨 환자의 메트포민 복용과 암 발생 억제 효과: 불멸의 시간 편향 통제를 중심으로

Effect of Immortal Time Bias Controlled Metformin for Cancer Development in Diabetic Patients

서화정
대한임상건강증진학회 (Korean Society For Health Promotion And Disease Prevention)|2022.03|Korean Journal of Health Promotion|제22권 제1호|pp. 40-47

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당뇨병암Cohort studies코호트연구Diabetes mellitusNeoplasmsMedication adherenceSelection bias표본선택편의약물 순응도
주제분류기타자연과학

초록

당뇨 환자의 메트포민 복용과 암 발생 억제 효과: 불멸의 시간편연구배경: 본 연구는 국민건강보험공단에서 제공한 표본코호트를 기반으로 당뇨 환자들에게 가장 먼저 고려되는 경구혈당강하제인 메트포민의 암 발생 억제 효과를 확인하고, 시간에 따른 편향이 암에 미치는 영향을 확인하는 것을 목적으로 하였다. 방법: 메트포민 순응군, 비순응군과 비복용군의 암 발생기간 비교를 위해 t-test를 실시하였다. 메트포민 복용에 따른 암 발생 위험도를 예측하는 변인들의 상대적 영향력을측정하기 위해 로지스틱 회귀모형을 수행하였다. 암 발생까지의 기간에 대한 메트포민 복용 효과의 분석을 위해 콕스회귀분석을 수행하였다. 결과: 메트포민 복용군이 비복용군에 비하여 평균적으로320일 늦게 발생하였다. 메트포민 비복용군(n=6,997)이 메트포민 순응군(n=16,132)보다 암 발생 오즈비가 1.11배(P=0.092) 측정되었다. 연령, 성별, 체질량지수, 콜레스테롤, 흡연 및고혈압을 보정한 모델 3의 위험비는 0.86이었다. 결론: 본 연구는 불멸의 시간 편향을 통제함으로서 최소복용 기간을 엄격하게 적용함에 따라 메트포민이 암 자체를억제하는 것보다 암 위험이 있는 환자의 암 발병을 지연시키는 데 효과적임을 확인하였다. 암 발생 위험인자들(고령, 남성)을 고려해야 하며, 메트포민 비복용군, 높은 콜레스테롤 등 암 발생 기간에 대한 위험이 높은 환자들에게 약제에대한 순응도 관리가 필요하다향 통제를 중심으로

Abstract

Background: This study aimed to determine the effectiveness of metformin as first line oral hypoglycemic agent in diabetes patients in inhibiting cancer incidence, on the basis of the sample cohort supplied by the National Health Insurance Service, and to ascertain the effects of time-related bias on the results. Methods: A t-test was performed to compare the time taken for cancer development between the compliant and non-compliant metformin users and the non-metformin users. Survival analyses for cancer patients, regarding the period time until cancer incidence, were performed according to metformin use through three models: model 1 adjusted for age and sex; model 2 further adjusted for body mass index, cholesterol, and smoking status; and model 3 further adjusted for hypertension. Results: The odds ratio for cancer development was 1.11 times higher for the non-metformin users (6,997) than for the metformin compliant users (16,132), which was significant at the 0.1 significance level. The age, sex, body mass index, cholesterol, smoking status, and hypertension-adjusted hazard ratio was 0.86. Conclusions: This study has confirmed that metformin is effective in delaying cancer development for patients at risk of cancer rather than in inhibiting cancer incidence itself, by strict application of metformin exposure, with which immortal time biases are controlled. It is therefore necessary to manage compliance with an agent, as well as to prescribe metformin for patients at high risk of cancer, giving consideration to the risk factors for cancer development (old age, being male) instead of focusing on metformin prescription, with the objective of inhibiting cancer development.

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