回顧許多既有的胰島素類似物，包括glargine和癌症風險的資料之後，他結論表示，分析廣泛的臨床試驗資料後顯示，使用胰島素glargine的各種癌症及乳癌風險並沒有比較高。無控制組的試驗則是支持包括乳癌等各種癌症的風險，並未因使用胰島素glargine而比美國流行病監督及最終結果資料庫(Surveillance, Epidemiology and End Results，SEER)的預估比率增加 。一篇大型長期隨機控制試驗顯示，沒有癌症顧慮。
Association but No Causality Between Insulin Glargine and Cancer Risk
By Becky McCall
Medscape Medical News
October 2, 2009 (Vienna, Austria) — Experts agree that there is an association but no established causal link between insulin analogues and cancer risk. Studies also show that insulin glargine (Lantus, Sanofi-Aventis) has no special risk over other insulin-based products.
Presenting at a symposium entitled Diabetes Therapy and Cancer, here at the European Association for the Study of Diabetes (EASD) 45th Annual Meeting, 6 experts commented on the potential link between insulin and insulin analogues (specifically insulin glargine) and cancer. Current president of the EASD, Ulf Smith, MD, from Sahlgrenska University Hospital in Goteborg, Sweden, said that he would not alter his clinical practice at the moment because the link between insulin analogues and cancer is too weak.
"An association is not causal," Dr. Smith said. "It shows a link between high insulin dose and increased cancer risk. This is a very new and complicated area and we have yet to answer all the questions."
He drew attention to the need for further research to understand the mechanism driving the association. "At the core of the matter is this: Is this due to high circulating insulin or is it the basic defect associated with both obesity and type?2 diabetes, that is, insulin resistance? Basic science evidence at the cellular level and in animals suggests that insulin resistance may be a very important factor. This cannot be determined from epidemiological studies," Dr. Smith observed.
After controversy surrounding the publication of German observational studies published earlier this year in the journal of the EASD, Diabetologia (2009; 52:1732-1744), 3 more studies were conducted on the basis of data derived from Sweden, Scotland, and the United Kingdom. The Swedish study showed a statistically significant link between insulin glargine and breast cancer (Diabetologia. 2009;52:1745-1754), the Scottish study found a nonsignificant link with breast cancer (Diabetologia. 2009;52:1755-1765), and the British study found no link with any type of cancer (Diabetologia. 2009;52:1766-1777).
Following these studies, the US Food and Drug Administration announced the launch of a safety review. Recently, Sanofi-Aventis also announced that they will begin a series of epidemiologic studies across Europe and the United States to expand the evidence base. Furthermore, the European Foundation for the Study of Diabetes, the research arm of the EASD, announced that it would provide €3?million ($4.4?million) to the EASD stand-alone research program aimed at funding new studies on the relation between diabetes and cancer over the next 3 years.
Craig Currie, PhD, medical epidemiologist from Cardiff University, Wales, and 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, highlighted a new study, which showed that diabetic patients treated with insulin were twice as likely to develop colon carcinomas as those taking metformin, and patients taking insulin alone had 4.5 times the risk for pancreatic cancer as those taking insulin plus metformin.
A Canadian study cited at the meeting but reported earlier in the year at the American Diabetes Association (Simpson SH et al. 69th Scientific Sessions, June 5-9, 2009; New Orleans, LA: abstract 1013-P) showed that patients receiving sulfonylureas, compared with those receiving metformin alone, had a 30% greater risk of being diagnosed with cancer. The same analysis showed that patients receiving insulin had a significant 67% increase in the likelihood of a cancer diagnosis, relative to those receiving sulfonylurea alone, and cancer risk was directly proportional to the increasing number of insulin prescriptions.
Jay Skyler, MD, professor of medicine, pediatrics and psychology at the University of Miami in Florida, referred to a list of studies on the cancer risk associated with various insulins. "In every case except for the German database, the hazard ratios span 1 and are therefore not statistically significant. If anything, the German database statistically suggests a decrease of cancer risk with glargine versus other insulins."
After reviewing the large volume of available data on cancer risks and insulin analogues, including glargine, he concluded that the analysis of extensive clinical trial data indicated that the risks for all cancers and breast cancers were not higher with insulin glargine than with comparators. "Uncontrolled trials provided supporting evidence that the risk of all cancers, including breast cancers, with insulin glargine was not increased, compared with expected rates from the US Surveillance, Epidemiology and End Results (SEER) database. A large long-term [randomized controlled trial] showed there was no cause for concern," he added.
"So my conclusion is that insulin glargine does not cause cancer and that newspaper headlines that accompanied the first appearance of the Diabetologia article were incorrect," Dr. Skyler asserted.
Dr. Smith, Dr. Currie, Dr. Gale have disclosed no relevant financial relationships.
European Association for the Study of Diabetes (EASD) 45th Annual Meeting: Symposium S14. Presented October 1, 2009.
