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ADA: Question Answered on Heart or Cancer Risk from Daily Insulin Glargine Use

Jun 14, 2012

Daily insulin glargine injections, begun during the early stages of type 2 diabetes, neither increased nor reduced the risk of heart attacks, strokes, cancer or cardiovascular-related mortality, researchers found in the largest and longest study of its kind….

The Outcome Reduction with Initial Glargine Intervention (ORIGIN) study randomized more than 12,500 people at high risk for, or in the early stages of, type 2 diabetes to either one daily injection of glargine (insulin) or standard care (no insulin), over a median of 6.2 years. Researchers found no difference among the two groups in cardiovascular outcomes or in the development of any type of cancer, suggesting that daily insulin injections to normalize glucose levels are not harmful when taken over long periods of time. Patients given insulin maintained glucose levels in the normal range (90-94 mg/dL) throughout the duration of the study. 

Some previous studies have suggested a link between insulin use and an increased risk of heart attacks, strokes and several kinds of cancer. But none have examined the long-term impacts of insulin use on serious cardiovascular outcomes and cancers in high-risk individuals, or have followed such a large study population.

Principal Investigator Hertzel Gerstein, MD, McMaster University Department of Medicine in Ontario, stated that, “People have been debating the question of whether there are adverse consequences to long-term insulin use for years.” “This study provides the clearest answer yet to that question: No, there are not.”

An analysis of data from five European countries — the largest of the three studies — found no increased risk of breast, prostate, or colorectal cancer with glargine compared with NPH, or “human” insulin, over 3 years, Peter Boyle, PhD, of the International Prevention Research Institute in Lyon, France, and colleagues reported here at the American Diabetes Association meeting.

A U.S. study similarly found no increased risk of any of those cancers among new glargine users compared with NPH insulin when they were followed for about a year, John Buse, MD, PhD, of the University of North Carolina at Chapel Hill, and colleagues reported.

But an analysis of Kaiser Permanente data, found a modest increase in breast cancer risk over 3 years among new glargine users compared with new users of other insulin (HR 1.6, 95% CI 1.0 to 2.8), Laurel Habel, PhD, of Kaiser Permanente in Oakland, Calif., and colleagues reported.

There was no increased risk of breast cancer, however, in patients in that database who’d been on insulin for a longer period of time and had switched from NPH to glargine.

“We think this may be a chance finding,” Habel said during a press briefing. “We don’t think there’s a good biological reason as to why you’d only see [cancer risk] in new users.”

Yet Habel cautioned that her study and the others didn’t follow patients long term, which would be necessary because cancers take a longer time to develop.

The study did confirm the presence of two previously known side effects of insulin – hypoglycemia and modest weight gain. However, both of these were minor, with patients gaining an average of 3.5 pounds over the duration of the study and experiencing a low rate of hypoglycemia, on average just over one episode per participant per year.

The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. The second coprimary outcomes included those above plus revascularization and hospitalization for heart failure. The researchers also looked at microvascular outcomes, incident diabetes, hyperglycemia, weight, and cancer incidence.

The Kaplan-Meier curves regarding cardiovascular events between the two arms were virtually superimposable, Gerstein said.

The only real difference was the “modest” weight gain (3 lbs. versus 1 lb.) and “modest” rate of hypoglycemia (6% versus 2%) associated with glargine during the study period.

“We now know what the risks are of taking insulin on a long-term basis, and they are low,” Gerstein said.

Practice Pearls:
  • Explain that risk of cancer in patients taking insulin glargine was not elevated in three large studies with follow-up times of about 3 years.
  • These studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • Note that one of the studies found a modest increased risk of breast cancer among new users of insulin glargine but not among those who switched from NPH to glargine.

Sturmer T, et al “Risk for cancer after initiation of insulin glargine versus NPH — A new user comparator drug cohort study” ADA2012. Habel L, et al “Insulin glargine and cancer risk: Kaiser Permanente California Cohort Study” ADA 2012.