Three Glargine Studies Find No Link to Cancer

On June 6, 2009, four articles about a possible link between the drug and incident cancer were simultaneously published. Although the authors were somewhat temperate in their conclusions, the lay press took this up with the screaming headline, "Insulin Treatment Causes Cancer!"

The public deemed insulin harmful to people with diabetes. And immediately, database scrutiny attempted to address this question.

Dr. James Meigs

Researchers want to know what we can learn about the usefulness of pharmacosurveillance databases for safety signals. And clinicians want to know if it’s safe to prescribe glargine.

If there is one take-home message from this group of studies, presented at the American Diabetes Association’s 2012 meeting – it’s "Yes. Glargine is safe and the benefits clearly outweigh the risks."

The other question is not so easy to answer.

Administrative databases can only tell us so much about patients and their experiences. Confounding is a crucial factor that often jeopardizes theses analyses. Missing data are the worst problem here. For instance, smoking status is typically missing in registry data. And yet smoking is common in diabetes and a huge risk factor for cancer. But missing smoking data do not equate to nonsmoking status. You can’t control for confounders that aren’t even measured.

Nor do these databases tell us much about exposure. Exposure time is easy enough to see in patients new to glargine. But we know nothing about prior exposure in those who switched to glargine. To accurately assess outcomes, we need to follow exposure with enough time to allow disease to develop in accordance with its natural history – which brings up another problem. Cancer has a very long latency. Its development can precede an exposure by years, creating the illusion that there is a relationship – when it was really present subclinically all along.

And finally – association does not imply causation. An association is just that – an association – until proven otherwise.

The punchline is this: It’s really hard to do these studies correctly. Cavalier publications of this or that exposure and risk are irresponsible and even harmful – particularly in the case of the glargine-cancer connection.

Insulin is lifesaving. We need it to treat diabetes. And we don’t want to limit our treatment options by prematurely worrying about signals coming up in poorly constructed studies.

Dr. James Meigs is director of the Massachusetts General Hospital’s clinical disease management research unit, in Boston. These remarks are taken from his presentation on the clinical implications of the findings presented by Dr. Boyle, Dr. Habel, and Dr. Stürmer. He had no financial disclosures.