Elsevier

The Lancet

Volume 374, Issue 9702, 14–20 November 2009, Pages 1677-1686
The Lancet

Articles
10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study

https://doi.org/10.1016/S0140-6736(09)61457-4Get rights and content

Summary

Background

In the 2·8 years of the Diabetes Prevention Program (DPP) randomised clinical trial, diabetes incidence in high-risk adults was reduced by 58% with intensive lifestyle intervention and by 31% with metformin, compared with placebo. We investigated the persistence of these effects in the long term.

Methods

All active DPP participants were eligible for continued follow-up. 2766 of 3150 (88%) enrolled for a median additional follow-up of 5·7 years (IQR 5·5–5·8). 910 participants were from the lifestyle, 924 from the metformin, and 932 were from the original placebo groups. On the basis of the benefits from the intensive lifestyle intervention in the DPP, all three groups were offered group-implemented lifestyle intervention. Metformin treatment was continued in the original metformin group (850 mg twice daily as tolerated), with participants unmasked to assignment, and the original lifestyle intervention group was offered additional lifestyle support. The primary outcome was development of diabetes according to American Diabetes Association criteria. Analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00038727.

Findings

During the 10·0-year (IQR 9·0–10·5) follow-up since randomisation to DPP, the original lifestyle group lost, then partly regained weight. The modest weight loss with metformin was maintained. Diabetes incidence rates during the DPP were 4·8 cases per 100 person-years (95% CI 4·1–5·7) in the intensive lifestyle intervention group, 7·8 (6·8–8·8) in the metformin group, and 11·0 (9·8–12·3) in the placebo group. Diabetes incidence rates in this follow-up study were similar between treatment groups: 5·9 per 100 person-years (5·1–6·8) for lifestyle, 4·9 (4·2–5·7) for metformin, and 5·6 (4·8–6·5) for placebo. Diabetes incidence in the 10 years since DPP randomisation was reduced by 34% (24–42) in the lifestyle group and 18% (7–28) in the metformin group compared with placebo.

Interpretation

During follow-up after DPP, incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group, but the cumulative incidence of diabetes remained lowest in the lifestyle group. Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Introduction

Prevention of type 2 diabetes mellitus is a major public health challenge because of its large effect on health. Diabetes affected an estimated 171 million people worldwide in 2000, and this number is projected to rise to 366 million by 2030, owing to increases in age, obesity, and urbanisation of the world's population.1 Diabetes was the world's fifth leading cause of death in 2000.2 In the Diabetes Prevention Program (DPP), a US multicentre randomised clinical trial, intensive lifestyle intervention or metformin prevented or delayed development of type 2 diabetes in adults at high risk because of raised fasting plasma glucose (5·3–6·9 mmol/L), impaired glucose tolerance (2-h postload glucose 7·8–11·0 mmol/L), and body-mass index of 24 kg/m2 or higher (≥22 kg/m2 in Asian Americans).3, 4 Development of diabetes5 was the primary outcome, and cardiovascular disease and its risk factors were secondary outcomes.

The Diabetes Prevention Program Outcomes Study (DPPOS) is a long-term follow-up of the DPP to investigate whether the delay in development of diabetes seen during the DPP can be sustained and to assess long-term effects of the interventions on health. In this first phase of DPPOS, we report the intervention effects on diabetes incidence, weight change, and cardiovascular disease risk factors and their treatment during 10 years of follow-up since DPP randomisation.

Section snippets

Participants

Recruitment and random assignment of DPP participants and other study methods have been described.3, 4, 6 We enrolled 3234 participants (68% women, 45% from ethnic and racial minority groups, and 20% aged 60 years or older) between 1996 and 1999. Participants were randomly assigned centrally to one of three interventions: intensive lifestyle (aimed to help participants to achieve and maintain 7% weight loss and 150 min or more per week of moderate-intensity physical activity); metformin 850 mg

Results

Enrolment into this follow-up study from the DPP cohort did not differ significantly by sex or ethnic origin, but was lower in women with a history of gestational diabetes than in those without and higher in participants who had developed diabetes by Sept 1, 2002, than in those without diabetes (table 1). Enrolment was also related to greater age, HbA1c, cholesterol concentrations, and in women, by lower weight and body-mass index (webappendix p 1). Table 2 shows DPPOS baseline characteristics.

Discussion

We report the first phase of the long-term follow-up (DPPOS) of the DPP cohort. The second phase is due to be completed in 2014. The DPP and other clinical trials12, 13, 14, 15, 16 have established the feasibility of interruption of the worsening of hyperglycaemia in overweight people who have raised fasting or postload glycaemia. 10 years after DPP randomisation, cumulative incidence of diabetes remained lower in the lifestyle and metformin groups than in the placebo group, despite changes in

References (28)

  • First versus repeat treatment with a lifestyle intervention program: attendance and weight loss outcomes

    Int J Obes

    (2008)
  • H Brown et al.

    Applied mixed models in medicine

    (1999)
  • PJ Diggle et al.

    Analysis of longitudinal data

    (1994)
  • Follow-up report on the diagnosis of diabetes mellitus

    Diabetes Care

    (2003)
  • Cited by (2299)

    View all citing articles on Scopus

    Members listed at end of paper

    View full text