Lantus and Cancer

Everyone seems to be talking about the recent report that insulin glargine (Lantus) might increase cancer rates. Needless to say, this is very upsetting news to a lot of people, although Lantus has been linked with cancer in the past.

But like most news stories, the facts aren't as simple as the summaries would indicate. If you like reading all the details, they're available here in full text, free.

The method of publishing these papers was interesting. Apparently the first study was submitted to the journal Diabetolgia last year. But the editors decided not to publish it without further evidence. So they commissioned three additional studies to see if the results could be reproduced. Those plus the original article are the four articles available at the journal’s Web site.

Was this irresponsible or responsible? Not publishing results suggesting some bad side effect of a drug might mean that people were harmed because they didn’t know about it. On the other hand, publishing preliminary results suggesting some bad side effect of a drug might mean that people were harmed because the huge publicity in the popular press that usually follows such news would scare patients who could be helped by the drug so they’d stop taking it.

This happened with the drug rosiglitazone (Avandia) last year. One analysis suggested that it caused heart disease, there was a huge glut of articles and blogposts saying Avandia could kill you, and a lot of people stopped taking it. Their A1cs then increased, and high A1cs also increase the risk of heart disease.

So it’s sort of a damned if you do and damned if you don’t situation.

Most patients don’t have the statistical skills to analyze research articles, especially meta-analyses, which try to combine results of numerous trials to see if they can come to overall conclusions. Because the patient populations, time frames, and endpoints being studied in different studies differ, this is difficult to do, and it’s easy to disagree with the results of a meta-analysis.

But regardless of whether or not we approve of the journal’s method of dealing with the Lantus-cancer articles, there are some things patients should understand.

In the editorial accompanying the articles, the authors make a few interesting points:

1. Type 2 diabetes is associated with increased rates of cancer of the colon, breast, and pancreas. People with type 2 diabetes have insulin resistance and hence need more insulin, either produced by their own beta cells or injected.

2. Cancers of the colon, breast, and pancreas have been associated with increased circulating levels of insulin in nondiabetic people. Obviously they wouldn’t be injecting insulin. They’re probably insulin resistant.

3. Metformin reduces the rates of cancer of the colon and pancreas but not cancer of the breast and prostate. (Metformin also seems to reduce the pancreatitis that can result from sitagliptin [Januvia].)

4. Insulin is a growth factor for both healthy cells and cancer cells in cell culture.

5. Evidence suggests that insulin doesn’t cause cancer, but it may increase the rate of growth of cancer cells that have been caused by something else.

6. Most elderly people have some early cancer cells. For example, 90% of men older than 90 years have prostate cancer cells. (The body often keeps these cells in check, or even destroys them.)

7. One early insulin analogue, B10Asp, was found to increase cancer growth in rodents and was never marketed. But "B10Asp would have passed the carcinogenicty testing to which insulin glargine was subjected and would now be in clinical use."

8. Lantus increases mitogenic potency (mitogenic means it causes cell division or transformation into another cell type, for example, a malignant one) six to eight times. The short-acting insulins (e.g., Novolog and Humalog) have little effect. Detemir (Levemir) seems to reduce the mitogenic potency in vitro, but the authors say that because of technical difficulties, this was difficult to measure.

There were all kinds of confusing factors in the four studies published by Diabetologia. For instance, they classified everyone diagnosed when older than 30 as type 2. We know that a lot of type 1s and LADAs aren’t diagnosed until later in life.

In the German study, the patients receiving regular insulin were taking larger doses than the patients taking insulin analogues. In another study, those taking only Lantus were older than those taking Lantus plus a bolus insulin. The ones taking only a basal insulin were most likely type 2s, who would need large doses of insulin, and we know that cancer rates increase with age among all groups.

In their editorial, the authors conclude that

1. “There is no evidence that insulin, however formulated, causes cancer.”

2. But “the growth of some tumor cells lines is clearly enhanced by insulin.”

3. “Circulating levels of endogenous insulin appear to be associated with cancer risk in obesity and other insulin-resistant conditions, including type 2 diabetes.”

4. “There is no evidence of harm in type 1 diabetes, or in males, or in premenopausal breast cancer.”

5. “On current evidence, the short-acting analogues do not appear to present a potential problem.”

In other words, there is evidence that very high levels of insulin, no matter what the source, may increase the growth of pre-existing cancers. People with insulin resistance (metabolic syndrome or type 2 diabetes) are at increased risk whether or not they inject insulin of any kind.

Hence, for us, the best approach would be to do whatever we can to reduce the amount of insulin that we need. Reducing our insulin resistance through exercise and, if possible, weight loss should help.

Another approach, available to everyone regardless of ability to exercise or lose weight, is to reduce the amount of carbohydrate we eat.

The less carbohydrate you eat, the less insulin you need. The less insulin you need (either your own or injected), the lower your risks of encouraging the growth of cancer cells. It seems me this is pretty easy to understand.

But some people don't seem to be able to grasp this. How long will it be before the American Diabetes Association stops telling people with type 2 diabetes to eat more carbohydrate and “Make starch the star”?