Use of an α-Glucosidase Inhibitor and the Risk of Colorectal Cancer in Patients With Diabetes: A Nationwide, Population-Based Cohort Study

Abstract

OBJECTIVEAcarbose, an a-glucosidase inhibitor, has been shown to have antineoplastic effects on colorectal cancer in biomarker studies. We assessed the association between acarbose use in patients with diabetes and incident colorectal cancer. RESEARCH DESIGN AND METHODSWe conducted a nationwide, population-based study using a large cohort with diabetes in the Taiwan National Health Insurance Research Database. Patients with newly diagnosed diabetes (n = 1,343,484) were enrolled between 1998 and 2010. One control subject not using acarbose was randomly selected for each subject using acarbose after matching for age, sex, diabetes onset, and comorbidities. Cox proportional hazards regression with a competing risks analysis was used to calculate the hazard ratios (HRs) and 95% CIs for the association between acarbose use and incident colorectal cancer for each eligible case-control pair (n = 199,296). RESULTSThere were 1,332 incident cases of colorectal cancer in the cohort with diabetes during the follow-up period of 1,487,136 person-years. The overall incidence rate was 89.6 cases per 100,000 person-years. Patients treated with acarbose had a 27% reduction in the risk of colorectal cancer compared with control subjects. The adjusted HRs were 0.73 (95% CI 0.63-0.83), 0.69 (0.59-0.82), and 0.46 (0.37-0.58) for patients using >0 to <90, 90 to 364, and ‡365 cumulative defined daily doses of acarbose, respectively, compared with subjects who did not use acarbose (P for trend < 0.001). CONCLUSIONSAcarbose use reduced the risk of incident colorectal cancer in patients with diabetes in a dose-dependent manner.Colorectal cancer is one of the most common cancers worldwide (1), causing an estimated 694,000 deaths in 2012 or 9.2% of all cancer-related deaths (2). Fecal occult blood screening and improved treatment in recent decades have reduced the annual global mortality of colorectal cancer (3). The incidence of colorectal cancer varies widely by geographic region and by degree of development. Although

Acarbose improved survival for Apc+/Min mice

“…We found that ACA improved median survival of Apc +/Min mice by 21.4% (Figure b, p = .0002) and that the longest‐lived mouse showed a 149% increase in lifespan compared to control. Our findings are in accord with the observation that diabetic patients receiving ACA display less colon cancer (Tseng, Tsan, Chan, Sheu, & Chen, ).…”

“…Hence, a high dose of ACA could be used to suppress polyposis and tumorigenesis. Furthermore, ACA given to diabetic patients showed less colon cancer supporting the use of ACA in treating people with FAP (Tseng et al, ). ACA is well‐tolerated in patients (Hanefeld & Schaper, ) and rapamycin has a black box describing it as an immunosuppressant.…”

2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications

“…A cohort of 275, 164 T2DM patients found no evidence for altered cancer risk for repaglinide or α-glucosidase inhibitors compared to insulin-based therapies or other oral glucose-lowering drugs [216]. In other reports, acarbose was associated with reduced the risk of incident CRC in patients with diabetes in a dose-dependent manner [238, 239]. Acarbose may alter the microbiota [240] and decreased the size of gastrointestinal adenomas in Apc knockout mice [241].…”

Thiazolidinediones and reduced risk of incident bacterial abscess in adults with type 2 diabetes: A population‐based cohort study

“…Patients with incident diabetes were further selected by excluding patients diagnosed with diabetes prior to January 1, 1998. 20 Based on data availability, the current study included patients with diabetes between January 1, 2000 and December 31, 2010 for analysis. The study was approved by the National Taiwan University Hospital Research Ethics Committee.…”