DPP and DPPOS Studies

Originally published March 23, 2020

This column highlights clinical trial data and landmark trials. Information for obtaining trial data and the references to the published articles are provided to facilitate discussion with your patients/colleagues. The trial is identified by the acronym and the National Clinical Trials Identifier. Primary outcome results are summarized.

Study title: Long-term Effects of Metformin on Diabetes Prevention: Identification of subgroups that benefitted most in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study1

Study title acronym: DPP (Diabetes Prevention Program) and DPPOS (Diabetes Prevention Program Outcomes Study)

ClinicalTrials.gov identifier: NCT00004992 and NCT00038727, respectively


1. Diabetes Prevention Program Research G. Long-term effects of metformin on diabetes prevention: Identification of subgroups that benefited most in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Diabetes Care. 2019;42(4):601-608.

2. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403.

3. Knowler WC, Fowler SE, Hamman RF, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374(9702):1677-1686.

4. Diabetes Prevention Program Research G. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: The Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015;3(11):866-875.

Sponsor: Funding was provided by multiple institutes of the National Institutes of Health (NIH), including NIDDK (U01-DK-048489), NICHD, NIA, NEI, NHLBI, NCI, ORWH and NIMHD, along with funding from the U.S. Department of Veterans Affairs, the Centers for Disease Control and Prevention, and the American Diabetes Association. Additional funding information can be found at http://care.diabetesjournals.org/content/42/4/601.full-text.pdf.

Study design: Between 1996 to 1999, the Diabetes Prevention Program (DPP), a multi-center, randomized, placebo-controlled trial, enrolled 3,234 adult participants (≥ 25 years of age) at high risk of developing diabetes (impaired glucose tolerance and elevated BMI) into one of three treatment arms: placebo (n=1082), metformin (n=1073; titrated to 850 mg twice daily) or intensive lifestyle intervention (n=1079). After completion of DPP, 86% of the surviving members of the metformin and placebo treatment groups further enrolled into the Diabetes Prevention Program Outcomes Study (DPPOS) for ongoing longitudinal follow-up (2002 to 2013) on metformin (unmasked) or no medication (i.e., placebo was discontinued). The current study represents the analysis of 15-year post-randomization follow-up data from the 2,155 metformin vs. placebo participants, to determine those subgroups for whom metformin treatment of prediabetes was most beneficial to prevent progression of disease.

Primary outcome: Progression to type 2 diabetes, based on: 1) abnormal results on annual OGTT (2-hr glucose ≥200 mg/dL) or semi-annual fasting plasma glucose (≥ 126 mg/dL); or 2) elevated hemoglobin A1c (A1C) (≥ 6.5%), via post-hoc analysis of 1,833 of 2,155 participants. 

Results: Confirming earlier published data of the DPP,2 15-year follow-up data demonstrated that metformin treatment of prediabetes was effective; specifically, metformin reduced the incidence of diabetes by 17% or 36% over 15 years, depending upon whether glucose criteria or A1C criteria, respectively, were used for diagnosis. By glucose criteria, metformin effects were greatest in those with higher baseline fasting glucose (≥ 110 mg/dL) and in women with a history of prior gestational diabetes mellitus (GDM); these effects appeared additive, with the greatest benefit coming to women with a history of both GDM and higher fasting glucose. By A1C criteria, metformin effects were greatest in those with higher baseline A1C (6.0 to 6.4%). In contrast to the original three-year DPP data, however, differing effects of metformin by age-group (25 to 25, 45 to 59 and ≥ 60 years) were no longer evident.

Summary: Results confirm a powerful beneficial effect of metformin to prevent progression to diabetes in the at-risk population.3,4 Knowing that certain subgroups receive the greatest benefit from metformin further validates a personalized medicine approach, helping practitioners to prioritize metformin use for those most likely to benefit, specifically those with higher fasting glucose or HbA1c at baseline and/or women with a history of GDM. The longer-term benefits of metformin therapy on microvascular disease, cancer or cardiovascular health in these specific subgroups are not yet known and will require further study.

Access additional resources and practical information[1] designed to enhance the care and treatment of your diabetes patients.

Kathryn Thrailkill, MD[2]About our experts: Kathryn Thrailkill, MD, Professor of Pediatrics, Division of Pediatric Endocrinology, Barnstable Brown Endowed Chair in Pediatric Diabetes Research, Barnstable Brown Diabetes Center, University of Kentucky, Lexington, Kentucky



Derick Adams, DO[3]Derick Adams, DO, Assistant professor, internal medicine, Division of Endocrinology, Endocrinology Fellowship associate program director, Barnstable Brown Diabetes Center, University of Kentucky, Lexington, Kentucky

  1. resources and practical information: http://www.diabetesselfmanagement.com/practical-diabetology/
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  3. [Image]: //cdn.diabetesselfmanagement.com/2019/04/Adams_DerickC.jpg

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