Published Online: March 13, 2013
William H. Herman, MD, MPH; Sharon L. Edelstein, ScM; Robert E. Ratner, MD; Maria G. Montez, RN, MSHP; Ronald T. Ackermann, MD, MPH; Trevor J. Orchard, MD; Mary A. Foulkes, PhD; Ping Zhang, PhD; Christopher D. Saudek,† MD; and Morton B. Brown, PhD; The Diabetes Prevention Program Research Group
Objectives: We report the 10-year effectiveness and within-trial cost-effectiveness of the Diabetes Prevention Program (DPP) and its Outcomes Study (DPPOS) interventions among participants who were adherent to the interventions.
Study Design: DPP was a 3-year randomized clinical trial followed by 7 years of open-label modified intervention follow-up.
Methods: Data on resource utilization, cost, and quality of life were collected prospectively. Economic analyses were performed from health system and societal perspectives. Lifestyle adherence was defined as achieving and maintaining a 5% reduction in initial body weight, and metformin adherence as taking metformin at 80% of study visits.
Results: The relative risk reduction was 49.4% among adherent lifestyle participants and 20.8% among adherent metformin participants compared with placebo. Over 10 years, the cumulative, undiscounted, per capita direct medical costs of the interventions, as implemented during the DPP, were greater for adherent lifestyle participants ($4810) than adherent metformin participants ($2934) or placebo ($768). Over 10 years, the cumulative, per capita non–interventionrelated direct medical costs were $4250 greater for placebo participants compared with adherent lifestyle participants and $3251 greater compared with adherent metformin participants. The cumulative quality-adjusted life-years (QALYs) accrued over 10 years were greater for lifestyle (6.80) than metformin (6.74) or placebo (6.67). Without discounting, from a modified societal perspective (excluding participant time) and a full societal perspective (including participant time), lifestyle cost <$5000 per QALY-gained and metformin was cost saving compared with placebo.
Conclusions: Over 10 years, lifestyle intervention and metformin were cost-effective or cost saving compared with placebo. These analyses confirm that lifestyle and metformin represent a good value for money.
Am J Manag Care. 2013;19(3):194-202
Over 10 years, among adherent participants, lifestyle intervention and metformin were effective and cost-effective for diabetes prevention compared with placebo.
Interventions to delay or prevent chronic diseases are often not cost saving in the short term, as intervention costs are incurred early and savings from complications averted accrue late in the natural history of disease.
In real-world clinical settings, lifestyle and metformin interventions are likely to be more effective and more cost-effective than they were during the randomized controlled clinical trial and its observational follow-up study.
Interventions for diabetes prevention represent a good value for money.
Previously, we reported the clinical and economic outcomes of an intent-to-treat analysis of the combined 10 years of the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study (DPP/DPPOS).1,2 In that analysis, participants were analyzed according to their randomized treatment group whether or not they adhered to their assigned treatment. In this paper, we report the results of an “on treatment” or “per protocol” analysis of DPP/ DPPOS. We assess outcomes by treatment group for participants who were adherent to their randomized assignments and compare the effectiveness and cost utility of the intensive lifestyle intervention (lifestyle) and the metformin intervention (metformin) with the placebo intervention (placebo).
Our previously published 10-year intent-to-treat analysis of DPP/ DPPOS used data from all randomized participants including those who did not adhere to their randomized treatments, and so likely underestimated both the effectiveness and the benefits of lifestyle and metformin. In real-world clinical practice, neither costs nor benefits are incurred by nonparticipants, but among participants, both intervention costs and benefits are likely to be greater. Our goal in this analysis of the DPP/ DPPOS is to extend our previous analyses to estimate the clinical effectiveness and cost-effectiveness of diabetes prevention among metformin participants who remained on treatment with metformin and lifestyle participants who succeeded in losing weight.
The DPP enrolled 3234 participants with impaired glucose tolerance and fasting hyperglycemia who were at least 25 years of age and had body mass index of /m2 or higher (/m2 in Asian Americans).3 The protocol and informed consent procedures were approved by all responsible institutional review boards. Participants signed written consent forms after discussion of all aspects of the study with study staff. For this analysis, we assigned costs related to finding the participants randomized to lifestyle and metformin but not the participants randomized to placebo. In estimating the costs of finding participants, we assumed that 10.4% of adults aged 45 to 74 years would be eligible to participate.4 We further assumed that potentially eligible subjects would be tested with a random capillary glucose level.5 If the capillary glucose level was >110 mg/dl, an oral glucose tolerance test (OGTT) would be performed6 and those with abnormal OGTTs would have a 15-minute visit with a physician to discuss the results. Based on the sensitivity, specificity, and reproducibility of the tests, we estimated that 12.8% of subjects screened would be eligible to participate in the DPP and that the average cost per eligible participant identified would be $173.
DPP. The goals for participants randomized to lifestyle were to achieve and maintain a weight reduction of at least 7% of initial body weight through diet and physical activity of moderate intensity, such as brisk walking, for at least 150 minutes per week.7 A 16-session core curriculum (given approximately weekly in individual participant sessions) and subsequent individual sessions (usually monthly) and group sessions with case managers were designed to reinforce the behavioral changes. The medication interventions (metformin and placebo) were initiated at a dose of 850 mg taken orally once a day. At 1 month, the dose was increased to 850 mg twice daily. Adherence was reinforced during individual quarterly visits with case managers. Standard lifestyle recommendations were provided to all groups through written information and an annual 20-to- 30-minute individual session that emphasized the importance of a healthy lifestyle. Mean follow-up at the end of DPP was 3.2 years. For the purposes of this analysis, we assumed that all subjects were enrolled in DPP for exactly 3 years.
DPP/DPPOS Bridge. At the end of the DPP, all participants, regardless of their random treatment assignment, were offered a group-implemented 16-session lifestyle intervention before their enrollment in the DPP Outcomes Study. During this bridge period, 40% of lifestyle, 58% of metformin, and 57% of placebo participants attended at least 1 session.8 The original lifestyle group was offered additional lifestyle support and was not encouraged to take metformin. The original metformin group was encouraged to continue metformin and to participate in the group lifestyle intervention. Those randomized to placebo stopped placebo and were encouraged to participate in the group lifestyle intervention. For the purposes of this analysis, we assumed that year 4 represented the DPP/DPPOS bridge.
DPPOS Maintenance. All active participants were eligible for continued follow-up during the DPPOS maintenance phase and 2766 of 3150 (88%) enrolled.1 These included 910 participants originally randomized to lifestyle, 924 to metformin, and 932 to placebo. For the purposes of this analysis, we assumed that years 5 to 10 represented DPPOS maintenance.
During DPPOS maintenance, the group lifestyle intervention was implemented as the Healthy Lifestyle Program (HELP) for all participants. HELP reinforced the original weight loss and physical activity goals and focused on current topics in nutrition, physical activity, stress management, and diabetes prevention. Although all participants were invited to attend all HELP sessions, many chose to attend fewer.
DPP participants initially randomized to lifestyle were also eligible to receive 2 BOOST sessions per year to reinvigorate their self-management behaviors for weight loss. Those randomized to metformin and placebo were excluded from BOOST sessions. The sessions reinforced specific behavioral self-management activities (eg, self-monitoring of fat, calories, and/or physical activity, as well as weight checks) important for weight loss and physical activity adherence and/or maintenance. In addition, the sessions promoted home-based behavioral self-management of weight and physical activity through the use of motivational campaigns.
Only metformin participants were encouraged to take metformin. One percent of non-diabetic participants in lifestyle and 3% of non-diabetic participants in placebo took metformin for diabetes prevention at any time during DPPOS maintenance.1 Lifestyle and placebo participants who took metformin during DPPOS maintenance were not excluded from the analyses.
Interventions for Participants With Diabetes. Participants identified with glucose levels diagnostic of diabetes at their semi-annual visits were seen within 6 weeks for glucose testing to confirm the diagnosis. Participants with confirmed newly diagnosed diabetes received individual counseling focused on self-monitoring of blood glucose, were provided with meters and test strips and encouraged to monitor their glucose levels once daily, and, for purpose of analysis, were maintained in their randomized intervention groups. Treatment for diabetes and surveillance for complications and comorbidities were performed by the participants’ own healthcare providers. Medications used by DPP participants for management of diabetes were recorded every 6 months on a drug summary form.
Subjects. For these analyses, we wished to assess resource utilization, costs, and outcomes by treatment group among participants randomized to lifestyle and metformin who adhered to their randomized interventions. We assumed that all participants randomized to lifestyle and metformin were adherent during year 1, when the interventions were initially implemented. We defined adherent lifestyle participants as those without diabetes who achieved and maintained 5% weight loss at > 50% of their semi-annual visits beginning at the end of year 1. We defined adherent metformin participants as those without diabetes who took > 80% of their prescribed metformin based on pill counts at > 80% of their semi-annual follow-up visits beginning at the end of year 1. We defined adherent placebo participants as all those randomized to the placebo group regardless of their adoption of lifestyle or metformin treatments during DPP, DPPOS Bridge, or DPPOS maintenance. Of the 1079 participants randomized to lifestyle, 587 (54%) were defined as adherent at the end of DPP year 1. Of 1073 participants randomized to metformin, 666 (62%) were defined as adherent at the end of DPP year 1. Participants in the lifestyle and metformin groups were defined as adherent until the time they became nonadherent or developed diabetes. For the most part, participants who were adherent at the end of DPP year 1 remained adherent for the duration of follow-up.
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