Managing Diabetes for Improved Health and Economic Outcomes

Transcription

1 Managing Diabetes for Improved Health and Economic Outcomes Based on a presentation by David McCulloch, MD Presentation Summary The contribution of postprandial glucose to diabetes progression and diabetes-related complications lends a new perspective to diabetes management. It has been long understood that tightly controlled glucose levels improve diabetes outcomes. Clinical studies and simulated models have estimated the impact of improved glycemic control on the economic outcomes of this disease, reporting that these cost benefits can be both short term and long term. The new economics of diabetes management emphasizes improved management through strategies such as better adherence to frequency of monitoring guidelines. The health and economic benefits have been demonstrated incrementally with improved glycemic status. Of additional importance to realizing economic benefits is the use of therapies that maintain lower glucose levels while minimizing side effects, hypoglycemic episodes, and longterm diabetes-related complications. Fast-acting insulins and the newer classes of insulin secretagogues, which target postprandial glucose, may pose distinct therapeutic advantages in this regard. Diabetes is an increasingly common condition that is increasingly expensive to society as a whole. Cardiovascular mortality is higher among individuals with diabetes than individuals without diabetes. 1,2 It is especially high among women with diabetes. 1,2 Diabetes is the leading cause of blindness, renal disease, and amputations, affects at least 5% of the population, and consumes at least 15% of healthcare costs expended by healthcare organizations. 3 The routine annual costs of caring for a person with diabetes are 3 to 4 times higher than for an age- and sex-matched person who does not have the disease. 3,4 The Diabetes Control and Complications Trial (DCCT) 5 concludes that improved glycemic control in type 1 diabetes will slow the progression and may even prevent, or reverse, some of the complications of diabetes. Moreover, the DCCT data published in 1996 clearly showed that improvement in blood glucose control is associated with a reduction in overall healthcare costs. 6 These reductions in diabetes-related complications could be expressed as average years gained free of particular diabetesrelated diseases, years free of first significant complication, and years of life gained (Table 1). One of the greatest problems in diabetes care is that, although most providers know that the ideal monitoring regimen for a patient with diabetes includes eye exams, foot exams, and hemoglobin A1c (HbA1c) tests, few patients actually receive these VOL. 6, NO. 21, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S1089

2 exams. In a cross section of patients, as shown in a 1999 study by Kaiser Permanente of California, 7 the proportion of patients actually receiving basic, common sense healthcare is low. It was found that by simply implementing a guideline, healthcare delivery can be improved in an organized manner. For example, the percentage of patients receiving HbA1c monitoring during the year directly increased from 51% to 84%. Similarly, serum lipid and urine protein monitoring increased from 49% to 75% and from 7% to 51% of patients, respectively. Favorable reductions in resource utilization were concomitant with these improvements in healthcare, and inpatient days decreased by approximately half during the 3-year study. Group Health Cooperative of Puget Sound is a large health maintenance organization with more than 500,000 enrolled members, including more than 18,000 patients with diabetes. Similar to the Kaiser Study, Group Health Cooperative of Puget Sound improved diabetes outcomes from poor levels to dramatically improved Table 1. Average Years Gained Free of Disease by Tight Glycemic Control ESRD = end-stage renal disease. Source: Reference 6. Average Years Gained Free of Disease Per Person Nationwide Blindness ,000 Albuminuria 9.7 ESRD ,000 Neuropathy 10.9 Lower limb amputation ,000 Years free of first significant complication 15.3 Years of life gained nationwide 611,000 levels and did so without an enormous additional expenditure of care to ensure that specific patients received the proper care at the opportune time. Improved information systems, identification of patients at greatest risk, and a proactive population-based approach to care were required. This concept mirrors the idea that one of the greatest challenges in diabetes management is delivering healthcare so that the most effective interventions reach people with diabetes who are most in need. A comprehensive program of planned, proactive healthcare was implemented in 1994 at Group Health Cooperative of Puget Sound. Overall changes in the care administered to members with diabetes were monitored for the first 3 years of implementing this program. 8 An initial concern was that the outreach efforts to identify people, to increase their access to supervision and glucose monitoring, and ultimately to improve their blood glucose control would be costly. Instead, we found within the first 3 years, the number of inpatient days per 1000 decreased by 26%, and the average length of hospital stay decreased by 10%. Although the number of primary care visits did not change, the number of specialty visits decreased by almost 25%. In parallel, during this program, the more appropriate use of angiotensinconverting enzyme (ACE) inhibitors and more appropriate and extensive use of metformin therapy caused pharmacy expenditures to increase. The proportion of pharmacy costs to overall diabetes costs is approximately 9%. Therefore, although pharmacy costs increased by 16%, overall cost of care for members with diabetes decreased by 11%. In the past few years, very impressive results have been seen from the United Kingdom Prospective Diabetes Study (UKPDS), in which newly diagnosed patients with type 2 diabetes were randomized to conventional or S1090 THE AMERICAN JOURNAL OF MANAGED CARE NOVEMBER 2000

3 ... MANAGING DIABETES FOR IMPROVED HEALTH AND ECONOMIC OUTCOMES... intensive efforts at glycemic control and followed for approximately 10 years. UKPDS demonstrated that intensive care for hyperglycemia improved blood glucose control and had better outcomes. 9 As shown in Figure 1, the separation of microvascular endpoints between the group receiving conventional therapy and the group receiving intensive therapy was apparent by approximately 9 years. The incidence of diabetesrelated deaths and myocardial infarction each displayed a separation between those 2 groups within a few years of improved glycemic control (Figure 2). When the UKPDS data were presented in Barcelona a few years ago, an epidemiologic analysis was performed. An approximately 1% decrease in HbA1c level in either the intensive or the conventionally treated group corresponded to a 17% reduction in all-cause mortality, an 18% reduction in myocardial infarction, and a 15% reduction in stroke. Reductions were also observed in the incidence of retinopathy and microalbuminuria. In practical terms, if physicians have patients with HbA1c concentrations of 11% to 13%, perhaps a decrease to 9% or 10% would affect the best outcome. At this point, glucose levels are not optimal, but substantial improvement in outcomes can, nonetheless, be realized. When the UKPDS followed the 2 treatment groups over time, an initial dramatic improvement in HbA1c and fasting blood glucose levels was observed in the intensively treated group; however, an inexorable, continual rise in glycemic levels was observed despite the continued intensive effort in disease management. This effect may be attributable to progressive beta cell deterioration. 10 The separation between the conventionally treated and intensively treated groups, as seen in the UKPDS, 9 is more evident with fasting blood glucose than it is with HbA1c, suggesting that initially fasting blood glucose may account for a significant portion of HbA1c levels. With most of the therapies currently available, fasting blood glucose levels can be fairly well controlled. Over time, however, even if fasting blood glucose is controlled by the various therapies at hand, postprandial blood glucose becomes more difficult to control. As a consequence, the HbA1c level begins to rise, despite the maintenance of low fasting plasma glucose concentrations, and this is reflected in a rise in HbA1c monitoring for hyperglycemia. These results were consistent with intensive treatment of type 1 diabetes, as conducted by the DCCT. 5 Although intensive diabetes management efforts improve glycemic control and, thereby, outcomes, the question remains whether it is cost effective from a societal point of view. Eastman and Keen performed a computerized model simulation, using the DCCT outcome data and other epidemiologic data, and tried to predict Figure 1. Incidence of Microvascular Endpoints in Patients with Type 2 Diabetes: Conventional Versus Intensive Therapy Incidence of Microvascular Endpoints (%) Time from Randomization (years) Conventional Intensive Source: United Kingdom Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet 1998;352: Reprinted with permission. VOL. 6, NO. 21, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S1091

4 if improved blood glucose could be maintained for a number of years. Their initial findings demonstrated that extrapolating from the DCCT model to a large population resulted in a substantial improvement in quality of life. 11 In a subsequent work, Eastman et al cited that if HbA1c is decreased and maintained at approximately 7.2%, long-term complications would be reduced and life span substantially extended. The incremental cost of quality-adjusted life-year was calculated to be $16, At $40,000 or $50,000, the interventions for many medical conditions are much more expensive than the $16,000 per quality-adjusted life-year for diabetes. It is generally believed that any intervention costing less than $50,000 per quality-adjusted life-year is probably well worth the effort. The potential weakness of the study by Eastman et al 12 is that it is a computer model and therefore completely dependent on the assumptions made by the model. The authors assume that the implementation of comprehensive care will be more expensive because of increased numbers of physician visits, tests, and other procedures. This investment may be offset, to some extent, by the decreased cost of laser therapy, dialysis, renal transplantation, and amputations, for example. However, this study uses epidemiologic data from several years ago and assumes that the current standard of care in the United States is poor. In the study model, baseline HbA1c for standard care is 10%, smoking prevalence is 25% to 30%, less than 50% of patients are screened for retinopathy, and less than 10% are screened for proteinuria. Figure 2. Incidence of Complications: Intensive Versus Conventional Therapy Incidence (%) Diabetes-related deaths P = 0.34 Incidence (%) Myocardial infarction P = Time from randomization (years) Time from randomization (years) Intensive Conventional Source: United Kingdom Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet 1998;352: Reprinted with permission. S1092 THE AMERICAN JOURNAL OF MANAGED CARE NOVEMBER 2000

5 ... MANAGING DIABETES FOR IMPROVED HEALTH AND ECONOMIC OUTCOMES... As a point of comparison, the plan members with diabetes at Group Health Cooperative of Puget Sound, without any special program targeted at improving HbA1c, have an average HbA1c of 7.6%, a smoking prevalence below 10%, and retinopathy and microalbuminuria screening in more than 70% to 80% of patients, respectively. Using these data as a baseline and implementing an intervention similar to the DCCT model, the incremental cost of quality-adjusted lifeyear, according to the model by Eastman et al, would be $150,000 to $200,000, a comparison that exemplifies the extent to which computer models are dependent upon assumptions. 12 Also, enormous improvements to quality of life and healthcare cost reduction can be accomplished by better organization of healthcare. Some interesting data were published by Health Partners in Minneapolis, another model of a wellorganized managed care organization. After taking a cross-sectional look at the population of approximately 3000 patients with diabetes who had HbA1c concentrations of 10%, 9%, 8%, 7%, and 6%, and their respective costs of care, Health Partners found a clear correlation between high HbA1c levels and increased medical costs (Figure 3). 13 Although Health Partners results were not conclusive, it was decided to test whether improving HbA1c, even in the short term, would affect reductions in cost of a real-life healthcare system. At Group Health Cooperative of Puget Sound, findings have been compiled on almost 5000 patients with diabetes, a cohort of continuously enrolled patients who had at least one HbA1c test per year for a 5-year period. 14 Of particular interest were those patients whose HbA1c level had dropped by more than 1% between 1992 and 1993 and was maintained at this lower level for at least 1 additional year. Those patients were compared in terms of utilization, hospitalizations, outcomes, and costs with patients whose HbA1c had not changed or risen over the same length of time. Although the annual cost of care increased in both groups, it increased more dramatically in those whose HbA1c values did not improve. A substantial cost savings was realized within just the first 2 to 3 years. Most notably, the number of patients with diabetes hospitalized in the years 1994, 1995, 1996, and 1997 was higher among those whose HbA1c values did not improve. In the first year studied, 1993, there was a transient increase in hospitalizations in the cohort of patients whose HbA1c values did improve, although this is presumed to be attributable to some triggering event a heart attack, lactic acidosis, or pneumonia that motivated the patients to improve their blood glucose control. Surprisingly, improved blood glucose control significantly decreased the number of primary care visits and sig- Figure 3. HbA1c Levels Influence Cost of Care Cumulative 3-Year Costs of Care ($) 11,629 10,424 10% 9% 8% HbA1c = hemoglobin A1c. Source: Adapted from reference HbA1c Level % 6% VOL. 6, NO. 21, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S1093

6 nificantly reduced annual patient costs. One explanation is that the patients sense of well-being improved their blood glucose control, and that translated into a less frequent need for primary care. 14 Table 2. Examples of Agents That Reduce Postprandial Glucose Levels Glucose Dependent Agents That Slow Down Absorption: Fiber Alpha-glucosidase inhibitors High protein/low carbohydrate diet Pramlintide Agents That Enhance Insulin Secretion in Response to Glucose Load: Nateglinide Meglitinides Glucose Independent Agents That Speed Up Insulin Action: Lispro Asp-28 GLP-1 (lag time) Agents That Enhance Insulin Secretion Independent of Glucose Load: Sulfonylureas Practical Considerations for Managing the Patient with Diabetes There are various approaches to improve blood glucose control in patients with type 2 diabetes such as closely monitoring HbA1c and fasting blood glucose concentrations. My initial focus is to achieve a fasting blood glucose level below 130 mg/dl through a combination of diet, exercise, metformin, self-monitoring, and bedtime insulin. Ideal maintenance levels for fasting blood glucose are below 140 mg/dl and below 7% for the HbA1c concentration. However, as pointed out earlier, even with acceptable levels of fasting blood glucose, the HbA1c concentration tends to drift up over time and is a signal to check blood glucose several times per day, including postprandially, and to apply interventions for improving postprandial blood glucose. Approaches for improving postprandial blood glucose levels include prescribing agents that slow down food absorption, such as alpha-glucosidase inhibitors and high fiber diets (Table 2). Although I believe the high protein/low fat/extremely low carbohydrate diets currently in fashion are dangerous and unproven, a diet low in carbohydrates may be helpful, because in such a diet, protein and fat must be converted to carbohydrates, which in turn slows the rise in blood glucose. Agents that speed up insulin action, such as lispro, Asp-28, and perhaps GLP-1, can also reduce postprandial glucose. Sulfonylureas traditionally have been used to stimulate insulin secretion in response to a glucose load; repaglinide may or may not be more effective than other short-acting sulfonylureas. New oral agents, such as the insulin secretagogue nateglinide, may reduce postprandial blood glucose more effectively than anything available thus far. Over the next several years, some of these agents may need to be added to our current armamentarium in an attempt to prevent or slow the inexorable rise of HbA1c levels in patients with long-term type 2 diabetes. Conclusion For both type 1 and type 2 diabetes, tight glycemic control improves health outcomes and can reduce long-term medical costs for the patient with diabetes. Evidence generated by research within a health plan now shows that cost savings, concomitant with improved health outcomes, were attainable within just a few years of improved healthcare for patients with diabetes. It is increasingly apparent that postprandial blood glucose is a reliable and independent measure of glycemic control and hyperglycemiainduced complications such as cardiovascular disease. These findings warrant further investigation to S1094 THE AMERICAN JOURNAL OF MANAGED CARE NOVEMBER 2000

7 ... MANAGING DIABETES FOR IMPROVED HEALTH AND ECONOMIC OUTCOMES... resolve the contribution of postprandial glucose to diabetes etiology, progression, and long-term complications, and to determine the potential of oral therapies that specifically target postprandial glucose.... REFERENCES Haffner SM. Coronary heart disease in patients with diabetes. N Engl J Med 2000;342: Kuusisto J, Mykkanen L, Pyorala K, Laakso M. NIDDM and its metabolic control predict coronary heart disease in elderly subjects. Diabetes 1994;43: American Diabetes Association. Diabetes Facts and Figures Available at: Accessed May 2, American Diabetes Association. Economic consequences of diabetes mellitus in the US in Diabetes Care 1998;21: Diabetes Control and Complications Trial Research Group. The effects of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329: Diabetes Control and Complications Trial Research Group. Lifetime benefits and costs of intensive therapy as practiced in the diabetes control and complications trial. JAMA 1996;276: Domurat ES. Diabetes managed care and clinical outcomes. Am J Manag Care 1999;5: McCulloch DK. Unpublished data. 9. United Kingdom Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet 1998;352: DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM. Diabetes Care 1992;15: Eastman RC, Keen H. The impact of cardiovascular disease on people with diabetes: The potential for prevention. Lancet 1997;350: Eastman RC, Javitt JC, Herman WH, et al. Model of complications of NIDDM. Diabetes Care 1997;20: Gilmer TP, O Connor PJ, Manning WG, et al. The cost to health plans of poor glycemic control. Diabetes Care 1997;20: Wagner EH, Sandhu N, Newton KM, et al. The impact of improved glycemic control on health care costs and utilization. Manuscript in preparation. VOL. 6, NO. 21, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S1095