New Studies 'Close the Loop' on Cancer/Insulin Link

Jim Kling

June 12, 2012

June 12, 2012 (Philadelphia, Pennsylvania) — The use of insulin glargine (Lantus, sanofi-aventis) in patients with type 2 diabetes is not associated with an increased risk for cancer, according to results from 3 epidemiologic studies presented here at the American Diabetes Association (ADA) 72nd Scientific Sessions.

Insulin is a growth factor, so there has been some worry that its use could affect cancer rates.

The 3 studies — the Northern European Database Study, the Kaiser Permanente Collaboration, and the MedAssurant Database — comprise the largest observational program conducted to detect an association between cancer risk and glargine, according to Sanofi, which sponsored the studies.

The Northern European Database Study, conducted in Denmark, Finland, Norway, Sweden, and Scotland, involved 447,821 patients using insulin and more than 1.5 million person-years of observation.

The average follow-up time was 3.1 years for patients on glargine and 3.5 years for those on other insulins. There was no evidence of an increased risk for breast cancer in women using glargine, compared with women using other insulins (HR, 1.12; 95% confidence interval [CI], 0.99 to 1.27). There was also no evidence of an increased risk for prostate cancer in men (HR, 1.11; 95% CI, 1.00 to 1.24) or of an increased risk for colorectal cancer in men and women (HR, 0.86, 95% CI: 0.76 to 0.98).

In addition, there was no evidence of an increased risk for any form of cancer combined or lung or pancreatic cancer.

In a press release, Peter Boyle, PhD, president of the International Prevention Research Institute in Lyon, France, stated that "these findings provide further evidence that insulin glargine does not increase the risk of cancer. The results of this study are reassuring from a patient and physician perspective."

The Kaiser-Permanente Collaboration was an American database study that used the Northern and Southern California Kaiser Permanente diabetes registries. It involved 115,000 patients with a median of 1.2 years of glargine use or 1.4 years of neutral protamine Hagedorn (NPH) insulin use.

There was no association between glargine and increased risk for breast cancer (HR, 1.0; 95% CI, 0.9 to 1.3), prostate cancer (HR, 0.7; 95% CI, 0.6 to 0.9), colorectal cancer (HR, 1.0; 95% CI, 0.8 to 1.2), or all cancers combined (HR, 0.9; 95% CI, 0.9 to 1.0).

A counting-of-dose subanalysis suggested a small increase in breast cancer in patients with 2 or more years of glargine use, but a counting-of-prescription subanalysis showed no such association. In a press release, lead study author Laurel Habel, PhD, a research scientist at Kaiser Permanente Northern California in Oakland, noted that results from this study should be viewed with caution because of the relatively short duration of glargine use, the low number of events, and the large number of associations examined.

The MedAssurant Database study — another American database study — relied on the MedAssurant healthcare database and involved 43,306 patients on glargine and 9147 on NPH. The mean duration of treatment was 1.2 years in the glargine group and 1.1 years in the NPH group. The study found no increased risk for breast cancer.

"This robust analysis of high-quality data from the United States shows that there is no association with an increased risk of cancer in users of insulin glargine," John Buse, MD, PhD, lead author of the 2 American studies, former president of the ADA, and director of the Diabetes Care Center at the University of North Carolina, in Durham, said in a press release.

Medscape Medical News spoke with Robert Ratner, MD, chief scientific and medical officer at the ADA, who found these large epidemiologic studies convincing. "We need to be very cautious with small epidemiological trials or trials that don't have adequate denominators. That's been a problem in the past," Dr. Ratner said, but with these new studies, "the controversy about insulin and cancer, I hope, is now coming to a close."

These 3 epidemiologic studies are particularly convincing when combined with the results of the Outcome Reduction With an Initial Glargine Intervention (ORIGIN) trial, a prospective randomized controlled trial also presented at the meeting. It showed no increased risk for cancer in 12,537 patients taking insulin glargine or receiving standard care.

This is "a full set of very large epidemiological trials using reliable methodologies to really assess the potential risk of cancer with insulin use. At least epidemiologically, there doesn't appear to be a relation between insulin therapy and cancer. More important, in a prospective randomized controlled trial setting, the ORIGIN trial, you have 7 years of follow-up with absolutely no signal of any effect on cancer. This is a closed circle," said Dr. Ratner.

The 3 epidemiologic studies were sponsored by Sanofi. Dr. Ratner reports consulting for Amylin, AstraZeneca, Novo Nordisk, sanofi-aventis, and Bayhill Therapeutics; receiving research support from Genentech, GlaxoSmithKline, Novo Nordisk, Roche Pharmaceuticals, sanofi-aventis, VeraLight, and Abbott Diabetes Care; and being a shareholder in Johnson & Johnson and Merck.

American Diabetes Association (ADA) 72nd Scientific Sessions: Symposium CT-SY13. Presented June 11, 2012.