Metformin and Gastrointestinal Cancer Development in Newly Diagnosed Type 2 Diabetes: A Population-Based Study in Korea

Abstract

INTRODUCTION: Clinical studies have produced conflicting results on the effects of metformin on gastrointestinal cancer development. We aimed to investigate the association between metformin use and stomach, colon, liver, and pancreatic cancer development among patients with newly diagnosed, drug-naïve type 2 diabetes. METHODS: This retrospective study evaluated propensity score-matched patients with newly diagnosed type 2 diabetes from the Korean National Health Insurance Service database. Metformin users were categorized into tertiles according to the cumulative dose or duration of metformin treatment, and the risks of gastrointestinal cancers were compared. RESULTS: Metformin users had reduced risks of developing stomach cancer (hazard ratio [HR]: 0.841, 95% confidence interval [CI]: 0.797–0.887), colon cancer (HR: 0.865, 95% CI: 0.822–0.91), and liver cancer (HR: 0.709, 95% CI: 0.675–0.746; P < 0.001). However, metformin users did not have a reduced overall risk of pancreatic cancer (HR: 1.335, 95% CI: 1.209–1.475; P < 0.001). The risks tended to decrease at higher cumulative doses and durations of metformin use, with significantly reduced risks of all 4 cancers at the highest cumulative dose (≥1,200,000 mg) and the longest duration (≥2,000 days) of metformin use. DISCUSSION: This population-based data suggest that metformin could be associated with reductions in the risks of stomach, colon, and liver cancers, as well a reduced risk of pancreatic cancer in some subgroups. Metformin has benefit as a first-line treatment for type 2 diabetes mellitus. A further role in cancer risk reduction could be studied in controlled trials.

Relationship between Changes in Blood Glucose and Blood Lipid Levels and the Risk of Thyroid Cancer in Patients with Type 2 Diabetes Mellitus

“…Serum HbAlc, TC, and TG levels were all influencing factors for thyroid cancer in patients with type 2 diabetes mellitus, while serum HDL-C level was a protective factor for thyroid cancer in patients with type 2 diabetes mellitus. This shows that serum HbAlc and blood lipid levels are related to thyroid cancer in patients with type 2 diabetes mellitus, and increased serum HbAlc, TC, and TG levels and decreased serum HDL-C levels are associated with an increased risk of thyroid cancer [ 24 , 25 ]. Regarding the clinical efficacy, Hb, MCHC, MCV, and adverse reactions and other indicators, this study did not find significant differences.…”

Effects of early medication treatment and metformin use for cancer prevention in diabetes patients: a nationwide sample cohort study in Korea using extended landmark time analysis

“…Metformin, a drug used to treat type 2 diabetes, is the most widely prescribed diabetes medication worldwide and has many beneficial effects, including anticancer effects [ 14 – 16 ]. Numerous studies have claimed that metformin could suppress the growth of cancer cells in multiple types of cancer including gastroenterological, colorectal, liver, lung, breast, and pancreatic cancer [ 17 – 24 , 46 – 48 ].…”

The relationship between the use of metformin and the risk of pancreatic cancer in patients with diabetes: A systematic review and meta-analysis

“…The results of 13 studies [13, 16, 18-24, 26, 31-33] were not statistically signi cant. Eight studies [15,17,24,25,28,29,35,36] reported that metformin signi cantly reduced the risk of pancreatic cancer, and three studies [27,30,34] reported an increase in the risk of pancreatic cancer.…”

“…Their basic characteristics are shown in Table 1. Among the 24 articles, ten were conducted in Asia (seven [17, 18, 22-24, 29, 33] in China and three [20,28,34] in South Korea), and the remaining 14 were conducted in no-Asia (six [14,16,25,27,30,35] in Britain, four [13,21,32,36] in the United States, two [15,26] in the Netherlands, 1 [31] in Italy and 1 [19] in Europe). Only two studies [22,24] are of low quality.…”