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

Abstract

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).

Figure 1. Trial profile

Screening and recruitment done in the Diabetes Prevention Program (DPP). OGTT=oral glucose tolerance test. ILS=intensive lifestyle intervention. m=month. *Includes 585 randomised to troglitazone before this treatment group was discontinued. †DPP enrolled participants during 3 years ending June, 1999. Participants had varying durations of DPP follow-up, dependent on their year of enrolment. ‡DPP participants who had not died or withdrawn consent as of Sept 1, 2002, were eligible. §Numbers of those examined in year 6 are lower than are those for the other years because the close of data for analysis occurred before all follow-up examinations were scheduled.

Figure 2. Mean weight changes

Weight changes for originally assigned treatment group since Diabetes Prevention Program (DPP) randomisation for (A) all participants, (B) those aged 25–44 years at randomisation, (C) 45–59 years, and (D) 60 years and older; and since enrolment in the present study for (E) all participants, (F) those aged 25–44 years, (G) 45–59 years, and (H) 60 years and older, including participants irrespective of whether they developed diabetes during follow-up. Webappendix p 2 shows numbers of those in every datapoint.

Figure 3. Cumulative frequency of diabetes

Development of diabetes since Diabetes Prevention Program (DPP) randomisation for (A) all participants, (B) those aged 25–44 years at randomisation, (C) 45–59 years, (D) and 60 years and older; and since enrolment in the DPPOS (Sept 1, 2002) for (E) all participants, (F) those aged 25–44 years at randomisation, (G) 45–59 years, and (H) 60 years and older. Webappendix p 6 shows numbers of participants remaining at risk of diabetes at every datapoint.

Figure 4. Incidence rates of diabetes during the three study phases of DPP, bridge, and DPPOS

The bars show diabetes incidence rates and the error bars 95% CIs. DPP=Diabetes Prevention Program.

Figure 5. Fasting glucose, glycosylated haemoglobin, and antidiabetic drug use

A=fasting glucose in mmol/L. B=HbA_1c (%). C=use of antidiabetic drugs (%). All participants were included irrespective of whether they developed diabetes during follow-up. Study-assigned metformin is excluded from antidiabetic drug use. Information for each data point is shown in webappendix p 7.