Cochrane for Clinicians

Putting Evidence into Practice

Can Pioglitazone Prevent or Delay Type 2 Diabetes in Patients with Prediabetes?


Am Fam Physician. 2021 Aug ;104(2):139-140.

Author disclosure: No relevant financial affiliations.

Clinical Question

How does pioglitazone (Actos) compare with other pharmacologic glucose-lowering agents and lifestyle interventions in the prevention or delay of type 2 diabetes mellitus in individuals with prediabetes?

Evidence-Based Answer

Pioglitazone prevents or delays the incidence of type 2 diabetes in individuals with prediabetes when compared with placebo (absolute risk reduction [ARR] = 11.3%; 95% CI, 0.9% to 15.6%; number needed to treat [NNT] = 9) or no intervention (ARR = 13.3%; 95% CI, 11.6% to 14.9%; NNT = 7). Compared with metformin, however, pioglitazone does not reduce the incidence of type 2 diabetes in those with prediabetes.1 (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)

Practice Pointers

Prediabetes is a condition with various definitions describing patients whose average blood glucose levels are higher than normal.1 Approximately 34.5% of the U.S. adult population has prediabetes, with a higher prevalence in men and a similar prevalence among all ethnic groups.2 The authors of this review sought to determine the effect of pioglitazone (a thiazolidinedione) on the prevention or delay of type 2 diabetes and its associated complications in individuals with prediabetes.

This review included 27 randomized controlled trials with 4,186 participants; most trials were conducted in outpatient settings, three of which were in the United States.1 Primary outcomes of this review were all-cause mortality, incidence of type 2 diabetes, and serious adverse events. Most studies identified individuals with prediabetes using the World Health Organization 1999, American Diabetes Association (ADA) 2003, or ADA 2010 diagnostic criteria for impaired fasting glucose or impaired glucose tolerance. A range of 15 to 30 mg of pioglitazone and varied doses of metformin (38 mg, 250 mg, and 750 mg) were typically used. The length of interventions ranged from six to 36 months.

Pioglitazone was compared with metformin, acarbose (Precose),

Author disclosure: No relevant financial affiliations.


show all references

1. Ipsen EØ, Madsen KS, Chi Y, et al. Pioglitazone for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020;(11):CD013516....

2. Centers for Disease Control and Prevention. National Diabetes Statistics Report 2020. Estimates of diabetes and its burden in the United States. Accessed December 22, 2020.

3. American Diabetes Association. 2. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes–2021. Diabetes Care. 2021;44(suppl 1):S15–S33.

4. Defronzo RA, Tripathy D, Schwenke DC, et al.; ACT NOW Study. Prevention of diabetes with pioglitazone in ACT NOW: physiologic correlates. Diabetes. 2013;62(11):3920–3926.

5. American Diabetes Association. 3. Prevention or delay of type 2 diabetes: Standards of Medical Care in Diabetes–2020. Diabetes Care. 2020;43(suppl 1):S32–S36.

6. GoodRx. Accessed January 6, 2021.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at



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