혈당강하제 단독요법 투여 당뇨병환자에서 암발생률 평가: 후향적 코호트 연구
Cancer Risk in Patients with Type 2 Diabetes on Antidiabetic Monotherapy: A Population Based Cohort Study Using National Insurance Health Service Database
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Diabetes is associated with cancer risk in the aging population. Observational studies have indicated the beneficial effects of metformin against breast cancer, making studies on the anticancer potential of antidiabetic drugs worthwhile. This study investigated cancer incidence in patients on antidiabetic monotherapy. Methods: Using National Health Insurance Service data (2002-2013), a retrospective cohort study that included type 2 diabetes mellitus (T2DM) patients was conducted. Study subjects were enrolled if they were ≥30 years old, on monotherapy for diabetes, and cancer-free. They were followed up for cancer occurrence or death, until December 31st, 2013. A Cox proportional hazard model analysis was conducted between metformin and sulfonylurea (including meglitinide) users, to determine cancer risk, with adjustment for age, gender, comorbidity index, dyslipidemia, hypertension, and T2DM duration. Results: The number of antidiabetic monotherapy-treated T2DM patients without a history of cancer was 9,554 (metformin, n = 5,825; sulfonylurea, n = 3,225; others, n = 504). During the follow-up period (mean, 2.04; IQR, 3.18 years), the cancer incidence rate was 5.48/100 and 5.45/100 patient-years for metformin and sulfonylurea, respectively. The hazard ratio (HR) for risk of cancer incidence in the metformin group was 0.74 (95% confidence interval [CI], 0.66-0.83; p < 0.0001), compared with sulfonylurea. Additionally, the HRs for risks of lung, liver, and stomach cancer were respectively 0.46 (95% CI, 0.31-0.66; p < 0.0001), 0.41 (95% CI, 0.31-0.54; p < 0.0001), and 0.51 (95% CI, 0.35-0.73; p = 0.0003). Conclusion: Antidiabetic therapy with metformin reduces cancer risk by 26%, specifically for lung, liver, and stomach cancer.
Abstract
Background: Diabetes is associated with cancer risk in the aging population. Observational studies have indicated the beneficial effects of metformin against breast cancer, making studies on the anticancer potential of antidiabetic drugs worthwhile. This study investigated cancer incidence in patients on antidiabetic monotherapy. Methods: Using National Health Insurance Service data (2002-2013), a retrospective cohort study that included type 2 diabetes mellitus (T2DM) patients was conducted. Study subjects were enrolled if they were ≥30 years old, on monotherapy for diabetes, and cancer-free. They were followed up for cancer occurrence or death, until December 31st, 2013. A Cox proportional hazard model analysis was conducted between metformin and sulfonylurea (including meglitinide) users, to determine cancer risk, with adjustment for age, gender, comorbidity index, dyslipidemia, hypertension, and T2DM duration. Results: The number of antidiabetic monotherapy-treated T2DM patients without a history of cancer was 9,554 (metformin, n = 5,825; sulfonylurea, n = 3,225; others, n = 504). During the follow-up period (mean, 2.04; IQR, 3.18 years), the cancer incidence rate was 5.48/100 and 5.45/100 patient-years for metformin and sulfonylurea, respectively. The hazard ratio (HR) for risk of cancer incidence in the metformin group was 0.74 (95% confidence interval [CI], 0.66-0.83; p < 0.0001), compared with sulfonylurea. Additionally, the HRs for risks of lung, liver, and stomach cancer were respectively 0.46 (95% CI, 0.31-0.66; p < 0.0001), 0.41 (95% CI, 0.31-0.54; p < 0.0001), and 0.51 (95% CI, 0.35-0.73; p = 0.0003). Conclusion: Antidiabetic therapy with metformin reduces cancer risk by 26%, specifically for lung, liver, and stomach cancer.
참고문헌 (21)
- Jee SH, "Fasting serum glucose level and cancer risk in korean men and women", JAMA, 293(2), pp.194~202 (2005)
- Vigneri P, "Diabetes and cancer", Endocr Relat Cancer, 16(4), pp.1103~1123 (2009)
- Hsu IR, "Metabolic syndrome, hyperinsulinemia, and cancer", Am J Clin Nutr, 86(3), pp.867S~871S (2007)
- Bowker SL, "Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin", Diabetes Care, 29(2), pp.254~258 (2006)
- Chen YC, "Cancer risk in patients aged 30 years and above with type 2 diabetes receiving antidiabetic monotherapy: A cohort study using metformin as the comparator", Ther Clin Risk Manag, 11, pp.1315~1323 (2015)
- Evans JM, "Metformin and reduced risk of cancer in diabetic patients", BMJ, 330(7503), pp.1304~1305 (2005)
- Libby G, "New users of metformin are at low risk of incident cancer: A cohort study among people with type 2 diabetes", Diabetes Care, 32(9), pp.1620~1625 (2009)
- Ruiter R, "Lower risk of cancer in patients on metformin in comparison with those on sulfonylurea derivatives: Results from a large population-based follow-up study", Diabetes Care, 35(1), pp.119~124 (2012)
- Thakkar B, "Metformin and sulfonylureas in relation to cancer risk in type II diabetes patients: A meta-analysis using primary data of published studies", Metab Clin Exp, 62(7), pp.922~934 (2013)
- Shaw RJ, "The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin", Science, 310(5754), pp.1642~1646 (2005)
- Rena G, "The mechanisms of action of metformin", Diabetologia, 60(9), pp.1577~1585 (2017)
- Del Barco S, "Metformin: Multifaceted protection against cancer", Oncotarget, 2(12), pp.896~917 (2011)
- Suissa S, "Metformin and the risk of cancer: Timerelated biases in observational studies", Diabetes Care, 35(12), pp.2665~2673 (2012)
- Chae YK, "Repurposing metformin for cancer treatment: Current clinical studies", Oncotarget, 7(26), pp.40767~40780 (2016)
- Eikawa S, "Immune-mediated antitumor effect by type 2 diabetes drug, metformin", Proc Natl Acad Sci USA, 112(6), pp.1809~1814 (2015)
- Bodmer M, "Metformin does not alter the risk of lung cancer: A case–control analysis", Lung Cancer, 78(2), pp.133~137 (2012)
- Zhang Z, "Reduced risk of lung cancer with metformin therapy in diabetic patients: A systematic review and meta-analysis", Am J Epidemiol, 180(1), pp.11~14 (2014)
- Zhang Z, "Metformin for liver cancer prevention in patients with type 2 diabetes: A systematic review and meta-analysis", The Journal of Clinical Endocrinology &Metabolism, 97(7), pp.2347~2353 (2012)
- Valent F, "Diabetes mellitus and cancer of the digestive organs: An italian population-based cohort study", J Diabetes Complications, 29(8), pp.1056~1061 (2015)
- Lee M, "Type 2diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in taiwanese: A representative population prospective cohort study of 800,000 individuals", BMC Cancer, 11(1), pp.20~ (2011)
- Tseng CH, "Metformin reduces gastric cancer risk in patients with type 2 diabetes mellitus", Aging (Albany NY), 8(8), pp.1636~1649 (2016)
