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作者：Becky McCall  
出處：WebMD醫學新聞

　　October 1, 2009 (奧地利維也納) — 歐洲糖尿病研究協會(EASD)第45屆年會發表的一篇流行病學研究，發現Metformin可以降低第2型糖尿病患的胰臟癌與大腸癌風險。
　　
　　研究共同作者、英國Bristol大學臨床科學系主任、糖尿病醫學部的Edwin Gale醫師表示，我們的觀察研究報告使用5年胰島素或metformin的癌症風險。我們發現，使用胰島素的病患發生大腸腫瘤的風險，是使用metformin者的2倍。胰臟癌風險差異更高：使用胰島素者的風險達4.5倍。這些是相當大的差異，認為metformin在胰臟癌這種致命率高的癌症有重要影響。
　　
　　這篇回溯世代研究，描述的是300家英國一般開業醫師的糖尿病患治療相關紀錄資訊。排除原本即有癌症的病患，且只收集2000年之後的資料。根據每年領用處方數估計使用的胰島素量(分成<7、7–10、11–15或>15)。研究者分析4,829名單用胰島素病患 (11,415病患-年)、5,035名使用胰島素加metformin (15,725病患-年)、以及30,421名單用metformin者(71,261病患-年)的資料。主要結果測量是第1個實質腫瘤的診斷。
　　
　　癌症粗發生率顯示，使用胰島素劑量最高組每1000病患-年有60件癌症，而胰島素加metformin組每1000病患-年有34件癌症。校正年紀、性別與抽菸狀態之後，胰島素加metformin組與單用胰島素組之間的比率依舊為真(5.73 vs 3.20)。
　　
　　共同作者、Cardiff大學流行病學家Craig Currie博士向Medscape Diabetes Endocrinology表示，單用胰島素組中，有明顯的劑量反應關係，劑量最高組的各種癌症比率是單用metformin者的6倍。這種劑量反應關係讓我們更瞭解因果關係，不過需要後續研究以獲得明確的答案。另一方面，metformin有可以降低癌症風險的重要性質，這些都需要進一步分析。
　　
　　會議主席、EASD現任理事長、瑞典Sahlgrenska大學醫院的Ulf Smith醫師表示，的確需要後續研究，以確認此一癌症比率關係是否因為高劑量胰島素、或是與第2型糖尿病有關的胰島素阻抗性。他表示，就胰島素本身而言，胰島素不無關係。細胞研究與動物研究的發現認為，胰島素阻抗性也可能是重要因素。此一流行病學研究顯示某種關聯，我們需要後續研究來獲得結論。
　　
　　Smith醫師表示，真正重要的結論是，metformin降低癌症風險。有關metformin的報導相當令人興奮，因為臨床研究顯示，以化療治療乳癌的病患在加入metformin時結果更好。本週另一篇令人振奮的報告顯示，metformin也可針對化療後殘存的、可能引起轉移的癌症幹細胞。我們現在開始非糖尿病患的臨床研究。
　　
　　Gale醫師表示，在未來幾年，將會有扣人心弦的研究議題出現，未來，我們需瞭解細胞代謝、細胞轉化與癌症之間的可能性，以及非糖尿病患使用metformin的可能性。瞭解更多胰島素阻抗性與癌症之間的關聯，將可朝向針對高風險族群進行篩檢的目標，可挽救數以千計的生命。
　　
　　Gale醫師、Currie醫師與Smith醫師皆宣告沒有相關財務關係。
　　
　　歐洲糖尿病研究協會(EASD)第45屆年會。發表於2009年10月1日。

Metformin Protects Against Cancer in Type 2 Diabetes

By Becky McCall
Medscape Medical News

October 1, 2009 (Vienna, Austria) — Metformin was found to reduce risk in pancreatic and colon cancers in patients with type?2 diabetes in an epidemiologic study presented here at the European Association for the Study of Diabetes (EASD) 45th Annual Meeting.

"Our observational study shows the risk of developing cancer over 5 years with insulin and with metformin. We found that patients on insulin were twice as likely to develop colon carcinomas than those on metformin. With pancreatic cancer there is a major difference between the 2 — patients on insulin alone had 4.5 times the risk. These are remarkably big differences and it suggests that metformin could play a significant role in pancreatic cancer — a particularly lethal form of cancer," said study coauthor Dr. Edwin Gale, MD, from the Department of Diabetic Medicine and head of the Department of Clinical Science at the University of Bristol in the United Kingdom.

The retrospective cohort study drew information relating to the treatment of diabetic patients from 300 British general practice records. Patients were excluded if they had had previous cancer and data were only collected from patients treated after the year 2000. Insulin exposure was estimated by the number of prescriptions filled per year (categorized as <7, 7–10, 11–15, or >15). The researchers analyzed data from 4829 patients taking insulin alone (11,415 patient-years), 5035 taking insulin plus metformin (15,725 patient-years), and 30,421 taking metformin alone (71,261 patient-years). The primary outcome measure was the diagnosis of the first solid tumor.

Crude cancer rates showed a notable 60 cancer events per 1000 patient-years in the group exposed to the highest amount of insulin alone, compared with 34 cancer events per 1000 patient-years in the insulin plus metformin group. After adjustment for age, sex, and smoking status, the same ratio was true for insulin plus metformin vs insulin alone (5.73 vs 3.20).

Craig Currie, PhD, a medical epidemiologist from Cardiff University in Wales, who coauthored the study, said: "In the insulin-only group, there was a distinct dose-response relationship, with a 6-fold increase in all forms of cancer in the highest group, compared with metformin monotherapy. This dose-response relationship brings us 1 step closer to suggesting a causal relationship, although further work needs to be done for a definitive answer. Metformin, on the other hand, does have important properties that appear to reduce cancer risk and we need to analyze these risks further," he told Medscape Diabetes Endocrinology.

Chairing the session, current EASD president Ulf Smith, MD, from Sahlgrenska University Hospital in Goteborg, Sweden, acknowledged that further research is needed to determine whether the relationship with cancer rates is due to high insulin dose or to the insulin resistance that is associated with type?2 diabetes. "There are reasons to involve insulin resistance per se. Findings at a cellular level and in animals suggest insulin resistance may be an important factor in this. This epidemiological study shows an association but we need further study to be conclusive," he said.

"A really important conclusion is that metformin reduces cancer risk," Dr. Smith said. "The story with metformin is very exciting because clinical studies show that patients treated with chemotherapy for breast cancer do considerably better when metformin is added. Another extremely exciting paper this week shows that metformin also targets cancer stem cells that remain after chemotherapy and can cause metastases. We are now starting clinical studies in nondiabetic patients."

Acknowledging the advent of an exciting research agenda over the coming years, Dr. Gale said that "in the future, we need to look at the possibility of links between cell metabolism, cell turnover, and cancer, and possibly the nondiabetic use of metformin. Understanding more about the link between insulin resistance and cancer and moving toward targeted screening of high-risk groups could save thousands of lives."

Dr. Gale, Dr. Currie, and Dr. Smith have disclosed no relevant financial relationships.

European Association for the Study of Diabetes (EASD) 45th Annual Meeting. Presented October 1, 2009.