Lower Risk of Cancer in Patients on Metformin in Comparison With Those on Sulfonylurea Derivatives

Abstract

OBJECTIVENumerous studies have suggested a decreased risk of cancer in patients with diabetes on metformin. Because different comparison groups were used, the effect magnitude is difficult to estimate. Therefore, the objective of this study was to further analyze whether, and to what extent, use of metformin is associated with a decreased risk of cancer in a cohort of incident users of metformin compared with users of sulfonylurea derivatives.RESEARCH DESIGN AND METHODSData for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. The association between the risk of cancer in those using metformin compared with those using sulfonylurea derivatives was analyzed using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant.RESULTSUse of metformin was associated with a lower risk of cancer in general (hazard ratio 0.90 [95% CI 0.88–0.91]) compared with use of sulfonylurea derivatives. When specific cancers were used as end points, similar estimates were found. Dosage-response relations were identified for users of metformin but not for users of sulfonylurea derivatives.CONCLUSIONSIn our study, cumulative exposure to metformin was associated with a lower risk of specific cancers and cancer in general, compared with cumulative exposure to sulfonylurea derivatives. However, whether this should indeed be seen as a decreased risk of cancer for the use of metformin or as an increased risk of cancer for the use sulfonylurea derivatives remains to be elucidated.

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

“…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).…”

“…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.…”

“…The remaining 21 articles were all full-reviewed. Bodmer et al 2012;Hsieh et al 2012;Ruiter et al 2012;Cardel et al 2014;Tsilidis et al 2014;Xu et al 2014) were enrolled in the meta-analysis. No study was included after hand-checking.…”

The Effect of Metformin on Colorectal Carcinoma in Type 2 Diabetes Mellitus Patients: A Markov Model Analysis

“…Annual mortality rate of general population(60-65 years old) 5.5% [33] Mortality of T2DM a patients without CRC b 0.154 [24] CRC morbidity 0.153% (0.068%-0.201%) [22][23][24][25]28] 0.197% (0.197%-0.242) [22,24,28] CRC specific mortality 5% (1.56%-10.248%) [26,27,33] 11.3% (4.21%-18.82%) [26,27,33] Non-CRC mortality 1.3% (0.335%-2.667%) [29,30] 3.3% (2.536%-4.397%) [26,33] growing body of evidence could back up the protective effect against CRC of metformin from in vivo and in vitro studies.…”

“…Transition probabilities between each state in this model were extracted from the included literatures published in English that investigated the therapeutic efficacy of metformin and/or other T2DM medications on CRC for T2DM patients without CRC (Table 1) [18,[22][23][24][25][26][27][28][29][30]. Literatures were retrieved from two databases of PubMed and Cochrane Library with the latest searching on September 27, 2016.…”