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Metformin Not the Only Treatment for Prediabetes

Pioglitazone in people with insulin resistance, prediabetes or diabetes is associated with a decreased risk for major adverse cardiovascular events, study data shows.

In people with insulin resistance, prediabetes or diabetes, pioglitazone is associated with a decreased risk for major adverse cardiovascular events, but may increase risks for heart failure, bone fracture, edema and weight gain, according to the researchers.

The study was done to to compare the risk of acute myocardial infarction, heart failure, and death in patients with type 2 diabetes treated with rosiglitazone and pioglitazone.

Meng Lee, MD, of the department of neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital in Taiwan, and colleagues conducted a systematic review and meta-analysis on nine randomized controlled trials from 1966 to May 2016 to determine the effects of pioglitazone in people with insulin resistance, prediabetes and type 2 diabetes.

39,736 patients who started on either pioglitazone or rosiglitazone were identified. During the six-year study period, the composite outcome was reached in 895 (5.3%) patients taking pioglitazone and 1,563 (6.9%) patients taking rosiglitazone. After extensive adjustment for demographic and clinical factors and drug doses, pioglitazone-treated patients had a lower risk of developing the primary outcome than did patients treated with rosiglitazone (adjusted hazard ratio 0.83, 95% confidence interval 0.76 to 0.90). Secondary analyses revealed a lower risk of death (adjusted hazard ratio 0.86, 0.75 to 0.98) and heart failure (0.77, 0.69 to 0.87) with pioglitazone, but no significant difference in the risk of acute myocardial infarction (0.95, 0.81 to 1.11). One additional composite outcome would be predicted to occur annually for every 93 patients treated with rosiglitazone rather than pioglitazone.

Pioglitazone was associated with lower risks for major adverse CV events and myocardial infarction and a trend toward reducing the risk for recurrent stroke (two trials; RR = 0.81; 95% CI, 0.65-1.01) among trial participants with prediabetes or insulin resistance.

There was an association between a lower risk for major adverse CV events and pioglitazone in trial participants with diabetes. There was no significant difference between trial participants with diabetes treated with pioglitazone and comparator groups for risks of MI and stroke.

When compared with a control group, pioglitazone was tied to an increased risk for heart and bone fracture, whereas no difference was observed in rates for all-cause mortality, any future cancer or bladder cancer risks. However, risks for edema, weight gain and hypoglycemia were higher among participants treated with pioglitazone compared with control groups.

Among people with prediabetes or insulin resistance, progression to diabetes was lower in groups treated with pioglitazone compared with those treated with placebo.

“The current meta-analysis of completed, randomized clinical trials indicates that pioglitazone has beneficial effects in reducing the risk of major adverse CV events in people with insulin resistance, prediabetes and type 2 diabetes,” the researchers wrote. “Rates of heart failure, bone fracture, weight gain and edema increased in pioglitazone-treated patients, while the occurrences of cancer and all-cause mortality did not rise. Weighing the risk–benefit profile, treatment with pioglitazone may be a reasonable choice in appropriately selected patients.

Among older patients with diabetes, pioglitazone is associated with a significantly lower risk of heart failure and death than is rosiglitazone. Given that rosiglitazone lacks a distinct clinical advantage over pioglitazone, continued use of rosiglitazone may not be justified.

Practice Pearls:

  • Pioglitazone reduces major adverse CV events in prediabetes, insulin resistance snd type2 diabetes.
  • Rosiglitazone is associated with a clinically significant higher risk of heart failure and death than is pioglitazone, but with no major difference in the risk of acute myocardial infarction.
  • Among people with prediabetes or insulin resistance, progression to diabetes was lower in groups treated with pioglitazone compared with those treated with placebo.

 

BMJ 2009;339:b2942