Memorandum

ACT NOW results published in NEJM; pioglitazone found to decrease rate of conversion from IGT to diabetes by 72% – March 27, 2011

Executive Highlights

  • Last last week, results from the ACT NOW study were published in the New England Journal of Medicine; pioglitazone was found to decrease the rate of conversion from impaired glucose tolerance to diabetes by 72%.

Late last week, results from the ACT NOW study were published in the New England Journal of Medicine. As a reminder, the study (n=427) evaluated the efficacy of pioglitazone in preventing diabetes in people with impaired glucose tolerance (IGT) (for previous coverage of ACT NOW, please see our July 31, 2010 Closer Look). After a median follow-up of 2.4 years, pioglitazone decreased the rate of conversion to diabetes by 72% compared to placebo in ACT NOW. As a reminder, in the oft-cited DPP (2002, NEJM), metformin was shown to decrease the rate of conversion from IGT to diabetes by 31%, and lifestyle modification was shown to decrease the rate of conversion by 58%. Although pioglitazone brought about a greater reduction in conversion to diabetes, treatment with the drug also caused an average weight gain of 3.6 kg (7.9 lbs) and had a higher rate of edema than observed with other treatments. All things considered, many believe that lifestyle modification (that results in modest weight loss) remains the best way to delay diabetes, as it does not have side effects, reduces blood pressure, improves lipid profiles, and more, although getting to a point where patients can make that happen remains challenging at best. The fact that pioglitazone causes weight gain may be a deterrent for people with prediabetes to use the drug, even though it increases insulin sensitivity; in addition, anti-TZD sentiments in the current post-Avandia era are also likely to make people more hesitant to use pioglitazone, even though the drug does not bear the same cardiovascular risk as Avandia. Regardless, until pioglitazone goes generic (in August 2012), its cost alone would be considered by most a prohibitive barrier to its use as a treatment for prediabetes although given the $200 billion spent on diabetes annually in the US alone, we think some healthcare economics data on those most at risk would be illuminating. We do look forward to seeing what generics companies do with TZDs going forward – another natural question is whether there are companies looking into combining them with other agents that cause weight loss.

To read the study in entirety, see here: http://www.nejm.org/doi/full/10.1056/NEJMoa1010949.

--by Vincent Wu and Kelly Close