Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals

Abstract

BackgroundMetformin protection against cancer risk in Orientals is uncertain. We examined the possible metformin effect on total, esophageal, gastric, colorectal (CRC), hepatocellular (HCC) and pancreatic cancers in a Taiwanese cohort.MethodsA representative sample of 800,000 was drawn from the Taiwanese National Health Insurance data of 2000. A cohort of 480,984 participants 20 years or older, diabetes-cancer-free on 1st January 2000 was formed and categorized as four groups by DM and metformin usage status. Eligible incident cancer events had to occur one year after the index date until the end of 2007. The Cox proportional-hazards model evaluated relative risk of cancer for treated DM patients with or without metformin. The covariates included age, gender, other oral anti-hyperglycemic medication, Charlson comorbidity index (CCI) score and metformin exposure dosage and duration.ResultsWith diabetes but no anti-hyperglycemic medication, cancer incidence density increased at least 2-fold for total, CRC and HCC. On metformin, total, CRC and HCC incidences decreased to near non-diabetic levels but to varying degrees depending on gender and cancer type (CRC in women, liver in men). Adjustment for other oral anti-hyperglycemic agents usage and CCI made the benefit of metformin more evident [hazard ratios (95% confidence intervals): total 0.12 (0.08-0.19), CRC 0.36 (0.13-0.98), liver 0.06 (0.02-0.16), pancreas 0.15 (0.03-0.79)]. There was a significant gender interaction with metformin in CRC which favored women. Metformin dosage for a significant decrease in cancer incidence was ≤500 mg/day.ConclusionsMetformin can reduce the incidences of several gastroenterological cancers in treated diabetes.

Reduced colorectal cancer incidence in type 2 diabetic patients treated with metformin: a meta-analysis

“…Finally, other factors like the different dosage of drugs may also result in the higher heterogeneity. For instance, in the study of Cardel et al (2014), the dose of the metformin use was approximately 450 DDD (defined daily dose) while it was 1000 DDD in the study of Lee et al (2011).…”

“…Table 1 shows that eight cohort studies (Oliveria et al 2008;Currie et al 2009;Libby et al 2009;Lee et al 2011;Hsieh et al 2012;Ruiter et al 2012;Tsilidis et al 2014;Xu et al 2014) including 175,432 cases and 126,967 controls, and three case-control studies (Yang et al 2004;Bodmer et al 2012;Cardel et al 2014) including 3133 cases and 15,774 controls were retrieved in the meta-analysis. Two studies were based on American (Oliveria et al 2008;Xu et al 2014), seven studies were based on European (Yang et al 2004;Currie et al 2009;Libby et al 2009;Bodmer et al 2012;Ruiter et al 2012;Cardel et al 2014;Tsilidis et al 2014), and two studies were based on Chinese (Taiwan) (Lee et al 2011;Hsieh et al 2012). All the studies were published from 2004 to 2014.…”

“…Several epidemiological studies reported significantly decreased CRC incidence among T2DM treated with metformin (Oliveria et al 2008;Currie et al 2009;Libby et al 2009;Lee et al 2011;Hsieh et al 2012;Ruiter et al 2012). However, other studies did not detect the relationship between metformin treatment and CRC risk among diabetes (Yang et al 2004;Bodmer et al 2012;Cardel et al 2014;Tsilidis et al 2014;Xu et al 2014).…”

Metformin suppresses the expression of Sonic hedgehog in gastric cancer cells

“…Metformin is a widely used anti-diabetic drug, which has been reported to exhibit potential anticancer activity (3). Previous studies have shown that metformin administration significantly reduces the incidence and mortality rates of various types of cancer, including gastric cancer (4)(5)(6).…”

Diabetes Mellitus Reduces Prostate Cancer Risk - No Function of Age at Diagnosis or Duration of Disease

“…Numerous human cancers are reported to be associated with DM. Increased risk of carcinomas of liver (Lee et al, 2011), colon (Jin, 2008), pancreas (Ben et al, 2011), kidney (Joh et al, 2011), endometrium (Weiderpass et al, 1997), esophagus (Jiang et al, 2012) and thyroid (Aschebrook-Kilfoy et al, 2011) is seen among patients with DM. Studies investigating the association between DM and prostate cancer (PCa), however, have shown a controversial result, although most of the studies revealed that DM may be associated with a lowering of the risk for PCa.…”