title: Association between use of oral-antidiabetic drugs and the risk of aortic aneurysm: a nested case-control analysis.
abstract: Pleiotropic effects on cardiovascular protection have been suggested in several oral antidiabetic drugs (OAD). The impacts of OADs on aortic aneurysm (AA) growth have been found in animal studies, but the evidence of their beneficial effects for AA protection in human are lacking. We investigated the relationship between OAD therapy and the risk of developing AA.
  
  
  
  We conducted a nested case-control analysis using the database extracted from Taiwan's National Health Insurance Research Database. The database consists of 1.2 million diabetic patients representing the majority of the type 2 diabetes population in Taiwan from 2000 to 2013. Cases were identified as those with either inpatient or outpatient diagnosis code of AA. One control was selected for each case matching on duration of follow-up, age, sex, urbanization, monthly income, severity of diabetes, and risk factor for AA. We identified variable classes of OADs, including metformin, sulfonylureas, thiazolidinedione (TZD), alpha-glucosidase inhibitors, meglitinide, dipeptidyl peptidase-4 (DPP-4) inhibitors prior to the development of AA.
  
  
  
  A total of 4468 cases diagnosed with AA and 4468 matched controls were identified. Metformin use, sulfonylurea use, and TZD were associated with lower risk of developing AA, odds ratio [OR] 0.72 (95 % confidence interval [CI] 0.64-0.80), 0.82 (95 % CI 0.74-0.92), and 0.82 (95 % CI 0.69-0.98), respectively. The effects of metformin and sulfonylurea on AA were dose responsive. Neither alpha-glucosidase inhibitors (OR 0.95; 95 % CI 0.81-1.11) nor DPP-4 inhibitors (OR 0.85; 95 % CI 0.68-1.07) was significantly associated with AA events.
  
  
  
  Metformin, sulfonylurea, and TZD treated patients were associated with lower risks of AA development, but not DPP-4 inhibitors or alpha-glucosidase inhibitor. The protective effects of hypoglycemic agents are further confirmed by the dose responsive relations in metformin and sulfonylurea groups.
authors: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.|Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
authors: Chien-Yi
authors: CY
authors: Hsu
authors: Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors: Yu-Wen
authors: YW
authors: Su
authors: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Medicine, Taipei City Hospital, Heping Fuyou Branch, Taipei, Taiwan.
authors: Yung-Tai
authors: YT
authors: Chen
authors: Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, No.325, Sec.2, Cheng-Kung Road, Taipei, Taiwan. tsaishihung@yahoo.com.tw.
authors: Shih-Hung
authors: SH
authors: Tsai
authors: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.|Taipei Veterans General Hospital, Taoyuan Branch, Taoyuan, Taiwan.
authors: Chun-Chin
authors: CC
authors: Chang
authors: Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Szu-Yuan
authors: SY
authors: Li
authors: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors: Po-Hsun
authors: PH
authors: Huang
authors: Department of Medical Research, Taipei Veterans General Hospital, 112, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan.|Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors: Jaw-Wen
authors: JW
authors: Chen
authors: Department of Medical Research, Taipei Veterans General Hospital, 112, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan. sjlin@vghtpe.gov.tw.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. sjlin@vghtpe.gov.tw.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan. sjlin@vghtpe.gov.tw.|Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. sjlin@vghtpe.gov.tw.
authors: Shing-Jong
authors: SJ
authors: Lin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001014:Aortic Aneurysm / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage; D005260:Female; D065089:Glycoside Hydrolase Inhibitors / Q000008:administration & dosage; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents
keywords: Aortic aneurysm; Diabetes mellitus; Oral antidiabetic drugs