二甲双胍似乎与结直肠癌风险降低有关

奥兰多——在消化疾病周(DDW)上发表的一项Meta分析显示，二甲双胍可能与2型糖尿病患者的结直肠癌(CRC)风险降低有关。

罗切斯特梅奥医院的Siddharth Singh医生报告称，磺酰脲类和胰岛素均与CRC风险降低无关，反而显示出风险增加的不显著趋势。未观察到CRC与噻唑烷二酮(TZD)类药物之间有关。

Siddharth Singh医生

糖尿病是明确的CRC危险因素，而且临床前和观察性研究已显示，抗糖尿病药物可能影响CRC风险。但不同降糖药物对CRC风险影响的差异并不明确。

Singh医生及其同事对15项评估降糖药物与CRC风险关联的研究进行了系统综述和Meta分析。各项研究之间存在明显异质性。具体包括5项病例对照研究、8项队列研究和2项随机对照试验，共涉及841,000例糖尿病患者中发生的近14,000例CRC。

分析结果显示，接受二甲双胍治疗者的CRC发病率降低了10%[10项研究；校正比值比(AOR)，0.90；95%置信区间(CI)，0.82~0.99；P=0.02]。即使仅分析高质量的观察性研究(7项研究；AOR，0.88；95%CI，0.79~0.98)，仍然得出一致的结果。

使用磺酰脲类(8项研究；AOR，1.12；95%CI，0.99~1.26；P=0.07)或胰岛素(10项研究；AOR，1.25；95%CI，0.91~1.71；P=0.17)的患者具有较高的CRC风险，不过均不具有统计学意义。

TZD与CRC风险无关(6项研究；AOR，0.95；95%CI，0.87~1.03；P=0.24)。

Singh医生认为，值得开展前瞻性队列研究或随机对照试验来评估二甲双胍对于成年2型糖尿病患者的化学预防效应。

这项Meta分析的主要局限性在于，具有显著性的结果仅见于观察性研究，而未见于随机对照试验的事后分析。而且存在多项残余混杂因素，包括没有校正肥胖、糖尿病指征和严重程度等。

Singh医生无利益冲突披露。

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By: NASEEM S. MILLER, Clinical Endocrinology News Digital Network

ORLANDO – Metformin may be associated with a reduced risk of colorectal cancer in patients with type 2 diabetes, according to a meta-analysis that included mostly observational studies.

Sulfonylurea and insulin were not associated with a reduced risk and showed a nonsignificant trend toward a higher risk for colorectal cancer (CRC). No association was noted between CRC and thiazolidinedione (TZD), Dr. Siddharth Singh reported at the annual Digestive Disease Week.

CRC incidence was reduced by 10% among patients who were on metformin (n = 10 studies; adjusted odds ratio [AOR], 0.90; 95% confidence interval, 0.82-0.99; P = .02). The results were stable when the analysis was restricted to high-quality observational studies (n = 7 studies; AOR, 0.88; 95% CI, 0.79-0.98).

CRC risk was higher in patients on a sulfonylurea (n = 8 studies; AOR 1.12; 95% CI 0.99-1.26; P = .07) or on insulin (n = 10 studies; AOR, 1.25; 95% CI, 0.91-1.71; P = 0.17). Neither result was statistically significant, however.

Dr. Singh said that the findings warrant prospective cohort studies or randomized controlled trials of the chemopreventive effect of metformin in adults with type 2 diabetes.

Diabetes is an established risk factor for colorectal cancer, and preclinical and observational studies have shown that antidiabetes drugs may affect CRC risk. The relative affect of various antidiabetes drugs on CRC risk is unclear, said Dr. Singh of the Mayo Clinic in Rochester, Minn.

Dr. Singh and his colleagues conducted a systematic review and meta-analysis of 15 studies evaluating the effects of metformin, TZDs, sulfonylureas, and insulin on colorectal cancer risk. There was considerable heterogeneity across the studies, which may be explained by study design, location, and whether the study accounted for the effects of other antidiabetic drugs, Dr. Singh said.

Five case-control studies, eight cohort studies, and two randomized controlled trials with a total of nearly 14,000 CRC cases in 841,000 diabetes patients were included in the meta-analysis.

TZD was not associated with CRC risk (n = 6 studies; AOR, 0.95; 95% CI, 0.87-1.03; P = .24).

One of the main limitations of the unpublished study was that the significant results were seen only in observational studies and not in post-hoc analysis of the randomized controlled trials. Also, there are residual confounding factors, including failure to adjust for obesity, and confounding by indication and severity of diabetes, Dr. Singh said.

"Before we take part in any proactive treatment regimen, we have to have well-designed, randomized controlled trials," said Dr. N. Jewel Samadder, assistant professor of medicine at the University of Utah, Salt Lake City. "However, the observational studies, and the meta-analysis that [follow], are certainly hypothesis driving. Diabetes itself is a risk factor [for CRC], and some of the medications may alter that risk," said Dr. Samadder, who was not involved in the study.

Dr. Singh had no disclosures. Dr. Samadder has received speaking and teaching honoraria from Cook.