Anne L. Peters, MD, CDE


December 26, 2012

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Hi. I am Dr. Anne Peters from the University of Southern California. Today I want to talk about preventing diabetes, but I want to discuss it in a somewhat different way from how we are used to thinking about it. First, we know that diabetes prevention is best addressed through lifestyle changes -- weight loss of 7% of body weight, maintaining that weight loss, and increasing physical activity -- but that does not always work for everyone. We know that some patients do not necessarily adhere to those changes, but other patients may not fit the typical paradigm.

I want to discuss a patient of mine. He is a man in his 50s. He is not overweight, although he has a family history of type 2 diabetes. His body mass index is about 23, which is not bad. One caveat, though, is that his son, who was about 12 years old when I first saw the patient, has type 1 diabetes.

When this patient came to see me about 8 years ago, his fasting blood sugars were in the prediabetic range -- around 105-108, and his hemoglobin A1c was also prediabetic, around 6.1-6.2, so he wanted to avoid getting diabetes. Of course I discussed lifestyle, but he did not have a lot of weight to lose and, in fact, he was fairly healthy. We discussed it, and the first drug he used was off-label pioglitazone because this drug probably helps prevent diabetes.

Metformin is the drug that is recommended by the American Diabetes Association, but frankly, no drug is approved by the FDA for diabetes prevention. In the case of this patient, because he was lean, because we really wanted to prevent progression, and because I did not know how he would tolerate metformin, I put him on a low dose of pioglitazone, and sure enough, he did well. His glucose values did not normalize, but his A1c came down a bit, to around 5.9-6, and stayed that way over the course of a number of years. Then the press came out about pioglitazone and the risk for bladder cancer, things that scare patients. I still think pioglitazone is a good drug, but in his case, he wanted to get off it, and we discussed trying metformin. He tried metformin, and he ended up having too many side effects to stay on it. Now I have a man who is no longer taking pioglitazone, does not tolerate metformin, and off of both of those medications his A1c is now creeping up; it is 6.2-6.3. His fasting sugars are now between 110 and 120, so I know he is drifting up.

What do you do with this patient? How do you prevent diabetes? There is no single right answer, but I was thinking of 2 different approaches. The first, which is untested, would be to treat him with a dipeptidyl peptidase-4 (DPP-4) inhibitor. A DPP-4 inhibitor, as we know, is easy to take, it is taken once a day, and may have positive long-term benefits on beta cells, although we do not really know if it helps to prevent diabetes. The other data we have are from the ORIGIN trial,[1] and in case you do not remember the ORIGIN trial, it is a big multicenter study with over 12,000 patients, looking at whether early treatment with insulin glargine in patients with prediabetes or diabetes prevented cardiovascular disease, and in the subset with prediabetes, whether it helped slow progression. Although the study was negative in terms of effect on cardiovascular risk, it did show that in those 1500 patients who had prediabetes and who received insulin early, it actually helped slow progression to true diabetes. This is one of those times when I sort of rolled my eyes at the data. Why give someone with prediabetes insulin? Most people do not want to get diabetes because they do not want to go on insulin, but when you give insulin to patients with early diabetes or prediabetes, it turns out to be much easier than when patients have more advanced diabetes. It is just [long-acting] basal insulin, rates of hypoglycemia are low with it, and it is easily tolerated. I gave the patient the choice of going on a DPP-4 inhibitor or going on a once-a-day shot of long-acting insulin in the hopes of preventing progression to overt diabetes. I summarized the literature as best I could for a sophisticated patient, and in the end, he chose to go on a once-a-day shot of long-acting insulin.

This experience taught me that insulin was helpful, that we do have this richness of clinical trials that are now available to us. But it also let me really perform individualized patient care because I could work with the patient, give him choices and options, and then figure out what was best for him. All along the way, I think that he has done really well with preventing himself from developing diabetes, which was the goal all along. This has been Dr. Anne Peters for Medscape. Thank you.