Ronald T. Ackermann

The Cost-Effectiveness of Lifestyle Modification or Metformin in Preventing Type 2 Diabetes in Adults with Impaired Glucose Tolerance

Context The Diabetes Prevention Program (DPP) showed that lifestyle changes or metformin effectively decreased the development of type 2 diabetes in adults with impaired glucose tolerance. The economics of these interventions is important to policymakers. Contribution This cost-effectiveness model estimates that the DPP life-style intervention would cost society about

Translating the Diabetes Prevention Program into the Community The DEPLOY Pilot Study

8800 and metformin would cost about

Adapting the Diabetes Prevention Program Lifestyle Intervention for Delivery in the Community The YMCA Model

29900 per quality-adjusted life-year saved. While lifestyle intervention had a favorable cost-effectiveness profile at any adult age, metformin was not cost-effective after age 65 years. Implications The cost-effectiveness of lifestyle intervention to prevent type 2 diabetes in high-risk individuals is within the range that American society typically finds acceptable for health care interventions. The Editors During the past half century, the number of persons with diagnosed diabetes in the United States has increased 4- to 6-fold (1). Recent large clinical trials from Asia, Europe, and North America have demonstrated that behavioral and medication interventions can delay or prevent the development of type 2 diabetes in persons with impaired glucose tolerance, which is defined by a plasma glucose level between 7.77 mmol/L (140 mg/dL) and 11.04 mmol/L (199 mg/dL) 2 hours after a 75-g oral glucose load (2-6). The Diabetes Prevention Program (DPP) randomly assigned 3234 nondiabetic persons 25 years of age or older with impaired glucose tolerance and fasting glucose levels between 5.27 mmol/L (95 mg/dL) and 6.94 mmol/L (125 mg/dL) to placebo; a lifestyle-modification program with the goals of at least a 7% weight loss and 150 minutes of physical activity per week; or metformin, 850 mg twice daily (4). The mean age of participants was 51 years, and the mean body mass index was 34.0 kg/m2; 68% were women and 45% were members of minority groups (4). The average follow-up was 2.8 years. Compared with the placebo intervention, the lifestyle intervention reduced the incidence of type 2 diabetes by 58% and the metformin intervention reduced the incidence of type 2 diabetes by 31% (4). We have previously described the costs of the DPP interventions and their cost-effectiveness within the 3-year trial period (7, 8). In this analysis, we project the costs, health outcomes, and cost-effectiveness of the DPP lifestyle and metformin interventions over a lifetime relative to the placebo intervention. Methods Clinical Trial The lifestyle intervention involved a healthy, low-calorie, low-fat diet and moderate physical activity, such as brisk walking. The lifestyle intervention was implemented with a 16-lesson core curriculum covering diet, exercise, and behavior modification that was taught by case managers on a one-on-one basis, followed by individual sessions (usually monthly) and group sessions with case managers (9). At the end of the study, 38% of participants in the lifestyle intervention group had lost at least 7% of their initial body weight. The metformin and placebo interventions were initiated at a dosage of 850 mg once a day. At 1 month, the dosage of metformin or placebo was increased to 850 mg twice daily. Case managers reinforced adherence during individual quarterly sessions (10). At the end of the study, 72% of participants in the metformin intervention group and 77% of participants in the placebo intervention group took at least 80% of the prescribed dose. All participants received standard lifestyle recommendations through written information and an annual 20- to 30-minute individual session that emphasized the importance of a healthy lifestyle (10). Simulation Model We assessed the progression from impaired glucose tolerance to onset of diabetes to clinically diagnosed diabetes to diabetes with complications and death by using a lifetime simulation model originally developed by the Centers for Disease Control and Prevention and Research Triangle Institute International. The model has a Markov structure and includes annual transition probabilities between disease states (11). In addition to disease progression, the model tracks costs and quality-adjusted life-years (QALYs). The model has been described elsewhere (11). For our analyses, we modified the model to include data from the DPP on progression, costs, and quality of life associated with impaired glucose tolerance, data from the United Kingdom Prospective Diabetes Study (UKPDS) on diabetes progression and complications, and new data on cost and quality of life associated with diabetes. A technical report describing the model is available. Supplement. Technical Report Disease Progression, Complications, and Comorbid Conditions Impaired Glucose Tolerance to Onset of Type 2 Diabetes We analyzed data from the DPP to assess the annual hazard of diabetes onset in the lifestyle, metformin, and placebo intervention groups. For patients receiving the placebo intervention, the annual hazard of diabetes onset was 10.8 per 100 person-years. At 3 years of follow-up, the risk reductions for the lifestyle and metformin interventions were 55.8% and 29.9%, respectively. In the base-case analysis, we assumed that the lifestyle and metformin interventions would be applied until diabetes onset and that the health and quality-of-life benefits associated with the interventions persisted until diabetes onset. Complications and Comorbid Conditions Associated with Impaired Glucose Tolerance We analyzed data from the DPP and other published sources to assess the prevalence of complications and comorbid conditions in participants with impaired glucose tolerance. At baseline, 6.0% of DPP participants had microalbuminuria and 0.4% had nephropathy. The DPP did not measure peripheral neuropathy, but previous studies found that the prevalence of neuropathy in persons with impaired glucose tolerance was 74% of that in persons with newly diagnosed type 2 diabetes (12) and 12.3% of persons with newly diagnosed type 2 diabetes have neuropathy (13). Therefore, we assumed that at baseline, 8.5% of DPP participants had clinical neuropathy. At baseline, 28% of DPP participants had hypertension, 45% had dyslipidemia, 7% were smokers, 1.1% had a history of cerebrovascular disease, and 2.0% had a history of myocardial infarction. No other complications were present. We assumed that during impaired glucose tolerance, microvascular or neuropathic complications would not progress. We assumed that hypertension and dyslipidemia developed at the rates observed in the DPP. On the basis of 2 large studies (14, 15), we assumed that the incidences of coronary heart disease and cerebrovascular disease in patients with impaired glucose tolerance were 58% and 56%, respectively, of those observed in patients with type 2 diabetes. We further assumed that nondiabetes-related mortality for persons with impaired glucose tolerance was the same as for persons with diabetes (16). Onset of Type 2 Diabetes to Clinical Diagnosis of Type 2 Diabetes In the DPP, participants were tested for diabetes every 6 months; diabetes was diagnosed at onset. In routine clinical practice, type 2 diabetes is estimated to develop 8 to 12 years before its clinical diagnosis (17, 18). In our base-case analysis, we therefore assumed that a 10-year delay occurred between the onset and clinical diagnosis of diabetes. Participants in the DPP had a mean hemoglobin A1c level of 6.4% at the onset of diabetes. Participants in the UKPDS had a mean hemoglobin A1c of 7.1% after a dietary run-in period but before randomization (13). Both DPP placebo participants and UKPDS participants received standard lifestyle recommendations. Accordingly, we assumed that during the 10-year interval between onset and clinical diagnosis of diabetes, patients were treated for type 2 diabetes and that hemoglobin A1c level increased at 0.07% per year from 6.4% to 7.1%. Complications and Comorbid Conditions Associated with Undiagnosed Diabetes We further assumed that between onset and clinical diagnosis of diabetes, microvascular and neuropathic complications progressed slowly, such that by clinical diagnosis of type 2 diabetes, their prevalence reached the level observed in the UKPDS cohort at randomization (13, 19, 20). We assumed that blood pressure and lipid levels progressed as they did in DPP participants and that cardiovascular complications occurred as they would in type 2 diabetes according to risk factors and hemglobin A1c level (21, 22). Clinical Diagnosis of Type 2 Diabetes to Diabetes with Complications and Death We assumed that after clinical diagnosis, all persons with type 2 diabetes received intensive glycemic management as described in the UKPDS (13). We modeled changes in hemoglobin A1c and diabetes treatments to reflect those observed in the UKPDS intensive therapy group. We based risk for retinopathy progression on UKPDS 38 (23), risk for nephropathy progression on UKPDS 64 (20), and risk for neuropathy progression on UKPDS 33 (13). We based risk for cerebrovascular disease on UKPDS 60 (22) and risk for coronary heart disease on UKPDS 56 (21). Costs Costs of Impaired Glucose Tolerance To estimate the total direct medical costs of impaired glucose tolerance, we considered the costs of the DPP interventions (the cost of identifying participants, implementing and maintaining the interventions, and monitoring and treating the side effects of the interventions) and the costs of the medical care outside the DPP (7). In analyses from the perspective of society, we included both direct medical costs and direct nonmedical costs. We did not include indirect costs because they are captured in the assessment of QALYs (24). Table 1 shows the total direct medical costs by treatment group, sex, and year in the DPP (7). Costs were higher in the lifestyle and metformin interventions than in the placebo intervention and higher in women than in men. Costs decreased over time in all 3 intervention groups but after year 1 tended to decrease more in the lifestyle than t

The Effect of Lifestyle Intervention and Metformin on Preventing or Delaying Diabetes Among Women With and Without Gestational Diabetes: The Diabetes Prevention Program Outcomes Study 10-Year Follow-Up

BACKGROUND The Diabetes Prevention Program (DPP) found that an intensive lifestyle intervention can reduce the development of diabetes by more than half in adults with prediabetes, but there is little information about the feasibility of offering such an intervention in community settings. This study evaluated the delivery of a group-based DPP lifestyle intervention in partnership with the YMCA. METHODS This pilot cluster-randomized trial was designed to compare group-based DPP lifestyle intervention delivery by the YMCA to brief counseling alone (control) in adults who attended a diabetes risk-screening event at one of two semi-urban YMCA facilities and who had a BMI>or=24 kg/m2, >or=2 diabetes risk factors, and a random capillary blood glucose of 110-199 mg/dL. Multivariate regression was used to compare between-group differences in changes in body weight, blood pressures, HbA1c, total cholesterol, and HDL-cholesterol after 6 and 12 months. RESULTS Among 92 participants, controls were more often women (61% vs 50%) and of nonwhite race (29% vs 7%). After 6 months, body weight decreased by 6.0% (95% CI=4.7, 7.3) in intervention participants and 2.0% (95% CI=0.6, 3.3) in controls (p<0.001; difference between groups). Intervention participants also had greater changes in total cholesterol (-22 mg/dL vs +6 mg/dL controls; p<0.001). These differences were sustained after 12 months, and adjustment for differences in race and gender did not alter these findings. With only two matched YMCA sites, it was not possible to adjust for potential clustering by site. CONCLUSIONS The YMCA may be a promising channel for wide-scale dissemination of a low-cost approach to lifestyle diabetes prevention.

Race/Ethnicity and Economic Differences in Cost-Related Medication Underuse Among Insured Adults With Diabetes The Translating Research Into Action for Diabetes Study

The Diabetes Prevention Program (DPP) demonstrated that a structured diet and physical activity intervention that achieves and maintains modest weight loss for over-weight adults with impaired glucose tolerance can significantly reduce the development of diabetes. Although tens of millions of American adults could benefit from access to the DPP lifestyle intervention, there currently is no available model for nationwide dissemination of this highly beneficial and cost-effective approach to diabetes prevention. In this article, the authors describe the evolution of adaptations to improve DPP lifestyle intervention implementation and dissemination by a strong community partner, the YMCA. They also provide information about early field research and an ongoing clinical trial that will provide information about the feasibility and effectiveness of applying this new model on a national scale.

Identifying Adults at High Risk for Diabetes and Cardiovascular Disease Using Hemoglobin A1c: National Health and Nutrition Examination Survey 2005–2006

CONTEXT Gestational diabetes (GDM) confers a high risk of type 2 diabetes. In the Diabetes Prevention Program (DPP), intensive lifestyle (ILS) and metformin prevented or delayed diabetes in women with a history of GDM. OBJECTIVE The objective of the study was to evaluate the impact of ILS and metformin intervention over 10 years in women with and without a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study. DESIGN This was a randomized controlled clinical trial with an observational follow-up. SETTING The study was conducted at 27 clinical centers. PARTICIPANTS Three hundred fifty women with a history of GDM and 1416 women with previous live births but no history of GDM participated in the study. The participants had an elevated body mass index and fasting glucose and impaired glucose tolerance at study entry. INTERVENTIONS Interventions included placebo, ILS, or metformin. OUTCOMES MEASURE Outcomes measure was diabetes mellitus. RESULTS Over 10 years, women with a history of GDM assigned to placebo had a 48% higher risk of developing diabetes compared with women without a history of GDM. In women with a history of GDM, ILS and metformin reduced progression to diabetes compared with placebo by 35% and 40%, respectively. Among women without a history of GDM, ILS reduced the progression to diabetes by 30%, and metformin did not reduce the progression to diabetes. CONCLUSIONS Women with a history of GDM are at an increased risk of developing diabetes. In women with a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study, both lifestyle and metformin were highly effective in reducing progression to diabetes during a 10-year follow-up period. Among women without a history of GDM, lifestyle but not metformin reduced progression to diabetes.

Changes in Health State Utilities With Changes in Body Mass in the Diabetes Prevention Program

OBJECTIVE—To examine racial/ethnic and economic variation in cost-related medication underuse among insured adults with diabetes. RESEARCH DESIGN AND METHODS—We surveyed 5,086 participants from the multicenter Translating Research Into Action for Diabetes Study. Respondents reported whether they used less medication because of cost in the past 12 months. We examined unadjusted and adjusted rates of cost-related medication underuse, using hierarchical regression, to determine whether race/ethnicity differences still existed after accounting for economic, health, and other demographic variables. RESULTS—Participants were 48% white, 14% African American, 14% Latino, 15% Asian/Pacific Islander, and 8% other. Overall, 14% reported cost-related medication underuse. Unadjusted rates were highest for Latinos (23%) and African Americans (17%) compared with whites (13%), Asian/Pacific Islanders (11%), and others (15%). In multivariate analyses, race/ethnicity significantly predicted cost-related medication underuse (P = 0.048). However, adjusted rates were only slightly higher for Latinos (14%) than whites (10%) (P = 0.026) and were not significantly different for African Americans (11%), Asian/Pacific Islanders (7%), and others (11%). Income and out-of-pocket drug costs showed the greatest differences in adjusted rates of cost-related medication underuse (15 vs. 5% for participants with income ≤

Identifying risk factors for racial disparities in diabetes outcomes: The translating research into action for diabetes study

25,000 vs. >

Healthcare Cost Differences with Participation in a Community-Based Group Physical Activity Benefit for Medicare Managed Care Health Plan Members

50,000 and 24 vs. 7% for participants with out-of-pocket costs >

A theoretically grounded systematic review of material incentives for weight loss: implications for interventions

150 per month vs. ≤