March 24th, 2011
Study Finds Pioglitazone Prevents Progression To Diabetes
Larry Husten, PHD
Pioglitazone significantly reduces the development of type 2 diabetes in people with impaired glucose tolerance, according to the results of the ACT NOW study published in the New England Journal of Medicine.
Ralph DeFronzo and colleagues randomized 602 patients with impaired glucose tolerance to pioglitazone or placebo. During a median followup of 2.4 years, diabetes developed in 16.7% of the placebo group versus 5% in the pioglitazone group (HR for pioglitazone 0.28, CI 0.16-0.49, p<0.001). The investigators calculated that 18 people needed to be treated for one year to prevent one case of diabetes. In addition to its beneficial effects on glucose metabolism, pioglitazone was associated with a decrease in diastolic blood pressure, reduced CIMT thickening, and increased HDL cholesterol. On a less positive note, pioglitazone caused a significantly larger weight gain (3.9 kg vs 0.77 kg) and more edema than did placebo.
The investigators acknowledged that the effect of pioglitazone on long-term diabetic complications has not been determined.
15 Responses to “Study Finds Pioglitazone Prevents Progression To Diabetes”
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And no idea if this will improve patient outcomes.
In this study, use of pioglitazone in patients wtih impaired glucose tolerance (IGT) (a) reduced the risk of diabetes; (b) improved diastolic BP, serum HDL and LFTs and (C) slowed progression of carotid intima–media thickening.
So Harlan, acknowledging that we don’t know if it improves patient outcomes, do you plan to prescribe (or withhold) pioglitazone for your patients with IGT?
I am always careful with the use of medications and want to be convinced that the benefit strongly outweighs the risks – so in this study pioglitazone reduces blood glucose levels and fewer progress to where they would be classified as diabetics. There is a slight difference in DBP and HDL. More weight gain and adverse effects with pioglitazone. And no idea how this might affect risk that the patient experiences. The study is too small and too short to tell us if this strategy favorably affects the patient’s risk. This patient category is quite large – this study is promising enough to do a larger study that would be powered for outcomes. But certainly not enough to start treating all these people.
It too early to implement this data into practice. 4 kg weight gain in 2.4 years period is unacceptable. Elderly(>60)IGT patients & patient with CHD with LV dysfunction might be still at risk of CHF. A risk benefit ratio still unclear. I am against hasty start of Pioglitazone 45gm to prevent DM in IGT patient.Lifestyle intervention & selective use of Metformine should be preferable choice.
I like what Victor Montori and colleagues wrote after DREAM (still seems relevant): Clinical use of glitazones to prevent diabetes is, at present, impossible to justify because of unproved benefit on patient important outcomes or lasting effect on serum glucose, increased burden of disease labelling, serious adverse effects, increased economic burden, and the availability of effective and less costly lifestyle measures.
http://www.bmj.com/content/334/7599/882.extract
Was this a manufacturer’s sponsored study? That would be another reason not to jump on the Pioglitazone bandwagon besides the ones articulated by Dr. Krumholz.
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It’s a pharmaceutical sponsored study (Takeda). The manuscript states that, “All results were transmitted to the Data Coordinating Center in Phoenix, Arizona, where they were recorded and audited and then sent to the Data Analysis Center in San Antonio. Takeda Pharmaceuticals provided financial support for the study but had no access to the data.”
Is this sufficient to assuage concerns of pharmaceutical influence on the study?
As much as most studies. This is where the FDA can be helpful, as they would get access to much more detail regarding the trial and potential biases.
If I need a drug in this scenario, I would use metformin. Much more experiece with this agent and fewer side effects..often weight loss. So, why wasn’t there a metformin arm? This is where the drug companies manipulate healthcare…and the reason for Federal funding for more robust cost effectiveness trials with hard endpoints.
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If you treat someone with a drug for diabetes and then note that their a1c and glucose levels are lower (therefore never meeting the definition of diabetes), have you really ‘prevented’ diabetes or just masked it by virtue of having people on treatment? Wouldn’t you want to see that an increased percentage of people in the treatment group remain free of diabetes when OFF he drug in some subsequent period before concluding that the development of diabetes had been altered? I can’t tell from the abstract that this was done – doesn’t look like it though.
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my opinion still life style modification is firs but it is diffucult by practice and second step is metaformin and pioglitazones .
Did anyone follow microalbinuria or retinal changes as pert of the study?
There have been 2 studies showing that for adult females, 2 cups of coffee a day delayed or prevented the development of AODM. Was the coffee driking noted in the study and assimilated with proper statistics?
Adam..excellent point…a real delay in diabetes off the drug would be a nice clinical indication of beta cell preservation(analagous to HTN and TROPHY)
Robin.as a caffeine addict I enjoy quoting evidence of potential health benefits..but I believe all the data is observational
With regard to caffeine and possible DM: this was a randomized study so, assuming decent randomization (don’t know what they did to evaluate that), the number of coffee drinkers should have been the same in both the placebo group and the pio group….
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Adam…reference please.