Diabetes drug pioglitazone could get personal: Neither panacea, nor peril

Lori Wiviott Tishler, MD, MPH

Assistant Professor of Medicine, Harvard Medical School

When I was in training, one of my beloved mentors declared, “I never use a drug until it’s been on the market for 20 years.” I was young enough then that I couldn’t fathom being a doctor for 20 years, let alone waiting two decades to use a new drug. As my career has progressed, I’ve seen many new drugs released to the market. Some of them are truly miraculous, bringing people longer, healthier, and more productive lives. Many of them have not withstood the test of time. More than a few have even been taken off the market. Even though the Food and Drug Administration diligently reviews each new medicine before it’s approved for use, we often learn much more about a drug after its release into the general population.

I reflected on that memory when I read a recent editorial in The New England Journal of Medicine (NEJM) about insulin resistance. In his editorial, the author tells us of the “long, strange trip” of a class of medications called thiazolidinediones, which help people who have type 2 diabetes or pre-diabetes to be more sensitive to the insulin that they make in their bodies. (Many diabetes medications work by helping the body lower its resistance to insulin in different ways.)

When they were first released, these medicines were widely accepted and adopted. We do, after all, have an epidemic of obesity and diabetes in the United States, and they seemed to work very well for people. They seemed a great alternative to insulin, which has to be injected. Then, after about 6 years on the market, these drugs began to be linked to liver disease and congestive heart failure — and maybe even cancer. Even though longer-term studies did not show that there was a definite risk of heart attack or cancer, these drugs became unpopular and fell into disuse. We were not willing to take a chance with our patients when we had other good options.

And yet, some researchers continued to wonder if there was any safe role for these very potent medications with their many positive effects, despite the concerns. The same NEJM issue as the editorial referenced above also contains a study that showed that certain carefully selected patients might, in fact, have fewer strokes if they took a medication called pioglitazone, which is in the thiazolidinedione class of medicines. Interestingly, the patients in this trial were already on extremely comprehensive stroke prevention regimens — and still they decreased their risk of a future stroke by 24%. These patients, all of whom were at risk of developing diabetes, had a slower rate of progression to diabetes as well.

What grabbed me about this story? First, it would seem that the drugs in question are neither panacea nor pariah. Pioglitazone, in fact, might a very good drug to prevent stroke in a very select population.

But, can we define that select population? That might be the most interesting tale of the past decades. Twenty years ago, we could only guess, based on certain characteristics of a patient, whether a medication would be effective. Today, we know certain people’s genetics make them better candidates for certain medications than other people. We are close to being able to tailor a medication to the patient at the level of his or her genes. When we are able to do this in an effective, safe, and efficient way, we will be able to deliver truly personalized medicine. As a clinician, I find this truly exciting. It would be wonderful to say to a patient, “This drug might have the following side effects — but I know they won’t affect you!”

My mentor may well have been right that it takes 20 years to know how a drug works and for whom it will work. He would not be surprised by the strange story of thiazolidinediones. He would undoubtedly be overjoyed by the idea that the past 20 years of laboratory and clinical research has brought us that much closer to truly personalized care.

Related Information: Reducing Sugar and Salt


  1. harold jitschak bueno de mesquita

    All very informative.
    Why should we keep shunning effective herbal medicines for diabetes [and in general]?
    Poterium spinosum is one of the highly effective anti diabetic herbs[given as a tincture]
    I learnt this some 30 years ago from Dr . R.F Weiss [ Lehrbuch der Phytotherapie, now also available in English], a very famous herbal doctor with huge experience.
    Since then I have seen enough patients, some of them with a HbA1C of 9 which dropped to 6 or lower with this tincture where a diet alone would not have done this[but I do very much stress and instruct about the diet and movement]
    Please look into this.
    Alas the tincture is not widely available but that maybe because of the small demand for it.

  2. Price Weston

    People who take Metformin live longer than non-diabetic age-matched controls. It’s the only diabetic drug which could potentially extend lifespans in healthy people. This has been known for more than 10 years and some life-extensionists have been taking it all that time.

    On the other hand, the ADA’s advice on diet (including the ACS, AMA, AHA, the NIH, the whole lot of medical acronyms) is horrible, 40 years old, and was bad 40 years ago. It is designed to maximize the carbs you consume and to consume it in a way that keeps your insulin up too high to enable stored fat to be mobilized for energy. Designed to keep people overweight and make weight loss very difficult. The only update has been advice to avoid trans fats. When I cut out trans fats more than 10 years ago after a heart attack, I was considered extreme for doing so. Back then, I switched to butter.

  3. Jimmie J. Flaherty

    In July of 2015, it was discovered that I got type 2 diabetes. By the end of the July month, I was given a prescription for the Metformin. I stated with the ADA diet and followed it completely for several weeks but was unable to get my blood sugar below 140. Without results to how for my hard work, I really panicked and called my doctor. His response? Deal with it yourself. I started to feel that something wasn’t right and do my own research. Then I found Rachel’s great blog (google ” HOW I FREED MYSELF FROM THE DIABETES ” ) . I read it from cover to cover and I started with the diet and by the next morning, my blood sugar was 100. Since then, I get a fasting reading between the mid 70s and 80s. My doctor was very surprised at the results that, the next week, he took me off the Metformin drug. I lost 30 pounds in my first month and lost more than 6 inches off my waist and I’m able to work out twice a day while still having lots of energy. The truth is that we can get off the drugs and help myself by trying natural methods

    • Maria Jasmine Freeman

      Very true; our diet improves our health, not the least diabetes. New studies are documenting its effect even on the brain-mainly through promoting healthy gut bacteria, and I would not be surprised it is the same with diabetes!
      I should assume you resorted to more grains, veggies, legumes, and sea -food, closer to the Mediterranean diet- the healthiest of all, right?! It would be appreciated if u could unveil that to us, for medical curiosity reasons, and also to benefit others.
      Dr Hana Fayyad

      • Lisa J

        That is a spam link that takes you, ultimately, to a $35 e-book (half off special!) that assures you doctors are killing you with treatment and their book, etc., can actually reverse diabetes entirely.

        When I was diagnosed e, I read that I never want my 2 hour post prandial numbers over 140 mg/dL. Originally, I was prescribed Metformin, and even a lettuce salad with grilled chicken would send it beyond that. I ended all high glycemic index carbs and started working out to improve my insulin sensitivity while asking my doctor to raise my Metformin (he assured me if I wasn’t over 180 I was fine). So, I kept exercising, avoiding bad carbs and watching my numbers.

        I have lost twenty pounds in less than two months since focusing on exercise and watching calories, too. It isn’t easy, and my doctor says I will probably quit taking medication after my next A1c test, only three months after diagnosis. I believe I am not ready. The easiest thing can knock you off track, you know?

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