OBJECTIVEBoth in vitro and in vivo studies indicate that metformin inhibits cancer cell growth and reduces cancer risk. Recent epidemiological studies suggest that metformin therapy may reduce the risks of cancer and overall cancer mortality among patients with type 2 diabetes. However, data on its effect on colorectal cancer are limited and inconsistent. We therefore pooled data currently available to examine the association between metformin therapy and colorectal cancer among patients with type 2 diabetes.RESEARCH DESIGN AND METHODSThe PubMed and SciVerse Scopus databases were searched to identify studies that examined the effect of metformin therapy on colorectal cancer among patients with type 2 diabetes. Summary effect estimates were derived using a random-effects meta-analysis model.RESULTSThe analysis included five studies comprising 108,161 patients with type 2 diabetes. Metformin treatment was associated with a significantly lower risk of colorectal neoplasm (relative risk [RR] 0.63 [95% CI 0.50–0.79]; P < 0.001). After exclusion of one study that investigated colorectal adenoma, the remaining four studies comprised 107,961 diabetic patients and 589 incident colorectal cancer cases during follow-up. Metformin treatment was associated with a significantly lower risk of colorectal cancer (0.63 [0.47–0.84]; P = 0.002). There was no evidence for the presence of significant heterogeneity between the five studies (Q = 4.86, P = 0.30; I2 = 18%).CONCLUSIONSFrom observational studies, metformin therapy appears to be associated with a significantly lower risk of colorectal cancer in patients with type 2 diabetes. Further investigation is warranted.
Given inconsistent trial results of sodium-glucose cotransporter 2 (SGLT2) inhibitors in addition to insulin therapy for treating type 2 diabetes mellitus (T2DM), a meta-analysis was performed to evaluate the efficacy and safety of this combination for T2DM by searching available randomized trials from PubMed, Embase, CENTRAL and ClinicalTrials.gov. Our meta-analysis included seven eligible placebo-controlled trials involving 4235 patients. Compared with placebo, SGLT2 inhibitor treatment was significantly associated with a mean reduction in HbA1c of -0.56%, fasting plasma glucose of -0.95 mmol/L, body weight of -2.63 kg and insulin dose of -8.79 IU, but an increased risk of drug-related adverse events by 36%, urinary tract infections by 29% and genital infections by 357%. No significant increase was observed in risk of overall adverse events [risk ratio (RR), 1.00], serious adverse events (RR, 0.90), adverse events leading to discontinuation (RR, 1.16), hypoglycaemia events (RR, 1.07) and severe hypoglycaemia events (RR, 1.24). No diabetic ketoacidosis events were reported. Further studies are needed to establish optimal combination type and dose.
. Meta-analysis of effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular outcomes and all-cause mortality among patients with type 2 diabetes mellitus.
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