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Original Contribution |

Health Economic Benefits and Quality of Life During Improved Glycemic Control in Patients With Type 2 Diabetes Mellitus:  A Randomized, Controlled, Double-Blind Trial FREE

Marcia A. Testa, MPH, PhD; Donald C. Simonson, MD
[+] Author Affiliations

From the Department of Biostatistics, Harvard School of Public Health (Dr Testa), and the Department of Medicine, Brigham and Women's Hospital, Joslin Diabetes Center, Harvard Medical School (Dr Simonson), Boston, Mass.


JAMA. 1998;280(17):1490-1496. doi:10.1001/jama.280.17.1490.
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Published online

Context.— Although the long-term health benefits of good glycemic control in patients with diabetes are well documented, shorter-term quality of life (QOL) and economic savings generally have been reported to be minimal or absent.

Objective.— To examine short-term outcomes of glycemic control in type 2 diabetes mellitus (DM).

Design.— Double-blind, randomized, placebo-controlled, parallel trial.

Setting.— Sixty-two sites in the United States.

Participants.— A total of 569 male and female volunteers with type 2 DM.

Intervention.— After a 3-week, single-blind placebo-washout period, participants were randomized to diet and titration with either 5 to 20 mg of glipizide gastrointestinal therapeutic system (GITS) (n=377) or placebo (n=192) for 12 weeks.

Main Outcome Measures.— Change from baseline in glucose and hemoglobin A1c (HbA1c) levels and symptom distress, QOL, and health economic indicators by questionnaires and diaries.

Results.— After 12 weeks, mean (±SE) HbA1c and fasting blood glucose levels decreased with active therapy (glipizide GITS) vs placebo (7.5%±0.1% vs 9.3%±0.1% and 7.0±0.1 mmol/L [126±2 mg/dL] vs 9.3±0.2 mmol/L [168±4 mg/dL], respectively; P<.001). Quality-of-life treatment differences (SD units) for symptom distress (+0.59; P<.001), general perceived health (+0.36; P=.004), cognitive functioning (+0.34; P=.005), and the overall visual analog scale (VAS) (+0.24; P=.04) were significantly more favorable for active therapy. Subscales of acuity (+0.38; P=.002), VAS emotional health (+0.35; P =.003), general health (+0.27; P =.01), sleep (+0.26; P =.04), depression (+0.25; P =.05), disorientation and detachment (+0.23; P =.05), and vitality (+0.22; P =.04) were most affected. Favorable health economic outcomes for glipizide GITS included higher retained employment (97% vs 85%; P<.001), greater productive capacity (99% vs 87%; P<.001), less absenteeism (losses=$24 vs $115 per worker per month; P <.001), fewer bed-days (losses=$1539 vs $1843 per 1000 person-days; P=.05), and fewer restricted-activity days (losses=$2660 vs $4275 per 1000 person-days; P=.01).

Conclusions.— Improved glycemic control of type 2 DM is associated with substantial short-term symptomatic, QOL, and health economic benefits.

Figures in this Article

MOST THERAPEUTIC studies of patients with diabetes have focused on the long-term complications of hyperglycemia1,2 or the short-term consequences of hypoglycemia.37 However, other potentially beneficial outcomes of improved glycemic control on quality of life (QOL), cognition, or symptoms for patients with either type 11 or type 2 diabetes mellitus (DM)811 generally have been reported to be minimal or absent. Although the direct and indirect costs of long-term diabetic complications have been established,1216 there has been less attention on evaluating the health economic impact of changes in glycemic control and QOL on costs associated with work loss and absenteeism, functional restrictions in daily activities, and use of health care services, such as physician and home nurse visits.

Some investigators have postulated that QOL and glycemic control are unrelated and that patients do not perceive any short-term benefits with improved glycemic control, thereby leading to noncompliance with complex regimens.8 Others have suggested that improvement in QOL with better glycemic control may be offset by the adverse effects and difficulty associated with intensive therapeutic regimens.1 However, a recent cross-sectional study of persons diagnosed as having type 2 DM found associations between high hemoglobin A1c (HbA1c) levels and a worsening in symptoms, mood, and well-being.17

Because these issues are critical for assessing the risks, benefits, and costs of new therapeutic regimens and disease management programs for type 2 DM, we evaluated the short-term changes in glycemic control, hyperglycemic and hypoglycemic symptoms, and treatment side effects on QOL, work productive capacity, functional restrictions, and health care use in patients with mild to moderate type 2 DM participating in a multicenter, randomized, double-blind, placebo-controlled trial of the controlled-release sulfonylurea, glipizide gastrointestinal therapeutic system (GITS).

Study Design

The trial comprised 4 phases: (1) a 1-week screening and washout period (week 1) if the patient was receiving prior hypoglycemic therapy; (2) a 3-week single-blind placebo period (weeks 1 to 3) prior to being randomized to either diet and placebo or diet and glipizide GITS in a 1:2 ratio; (3) a 4-week double-blind titration for placebo and glipizide GITS starting at 5 mg with incremental increases to a higher dose (10 mg, 15 mg, and 20 mg) if the fasting plasma glucose goal of levels reaching at least 6.4 mmol /L (115 mg/dL) was not achieved (weeks 4 to 7); and (4) an 8-week maintenance on the final titration dose (weeks 8 to 15).

Patient Population

Eligibility criteria included men and women with type 2 DM who were at least 30 years old, were not pregnant, and had been treated with sulfonylurea and diet or diet alone for a minimum of 3 months. Patients were excluded if they had a body weight of less than 80% or more than 160% of the ideal weight set by the Metropolitan Life Insurance tables; had received insulin for longer than 1 week 3 months before enrollment; had ketoacidosis during the past year; or showed evidence or had a history of significant confounding illness or substance abuse. For the QOL assessments, patients were required to read either English or Spanish at the sixth-grade level.

During the placebo phase, patients were randomized if they met one of the following criteria: (1) fasting plasma glucose levels between 7.8 mmol/L (140 mg/dL) and 13.9 mmol/L (250 mg/dL) or (2) HbA1c levels of more than 6% (by the end of week 2), if fasting plasma glucose levels were less than 7.8 mmol/L (140 mg/dL) and if plasma glucose levels measured 1 and 2 hours after drinking a liquid mixed meal (Sustacal, Mead Johnson & Co) were at least 11.1 mmol/L (200 mg/dL). We received approval from institutional review boards and obtained informed consent from participants.

Clinical and Laboratory Evaluations

During the single-blind placebo period clinicians measured HbA1c, fasting blood and plasma glucose, fasting insulin, C-peptide, Sustacal challenge, and lipid and microalbuminuria levels. Home blood glucose monitoring levels were also recorded. Clinical and laboratory evaluations were repeated at 1, 2, 3, 4, 6, 8, 10, and 12 weeks after randomization. Clinicians also assessed patients' compliance with home blood glucose monitoring, diet requirements, and diary completion.

Patient QOL and Self-assessments

Quality of life, days worked, health related days missed, restricted activity-days, and health care use were assessed at screening, randomization, and 4, 8, and 12 weeks postrandomization (study weeks −1, 3, 7, 11, and 15). Quality-of-life outcomes included the following: 5 visual analog scales (VASs) of perceived health; mental and emotional health; self-reported cognitive function; general health perceptions; and symptom distress. Assessment instruments,1820 rationale for QOL measurement, and analytical methods21,22 are detailed elsewhere.

Use of health services, employment history, work attendance, and short-term morbidity as reported by the patient included hospitalizations, ambulatory care visits, home health care visits, general household assistance, telephone calls to health care professionals (during the previous 4 weeks), employment, number of days worked, number of days missed, activity restrictions, and bed-days caused by health problems (during the previous 7 days). Patients also completed a home diary that included daily assessments of perceived hypoglycemic and hyperglycemic reactions with an immediate subsequent home blood glucose measurement; every-other-week assessments (for 2 days each week) of the analog overall health rating and corresponding home blood glucose measurement taken before breakfast and before bedtime; and a monthly assessment of 43 diabetes-specific symptoms6,7 with corresponding home blood glucose measurements completed 4 times a day before breakfast, lunch, dinner, and bedtime.

The costs of lost earnings were based on the average annual wages of male and female workers by age as reported by the Bureau of Census23 ($116 per day for men and $74 per day for women between the ages of 35 and 65 years). Production losses for a nonemployed individual were assumed to be 64% of that of an employed person.24

Study Accrual

A total of 594 patients from 62 centers in the United States were randomized to either placebo and diet management (n=201) or glipizide GITS and diet management (n=393). In the placebo group, 30 patients (14.9%) were withdrawn prior to the study's completion compared with 37 patients (9.4%) who were withdrawn in the glipizide GITS group (P=.055). Of these 594 patients in whom efficacy and safety were assessed, 569 (192 taking placebo and 377 taking glipizide GITS) met the inclusion criteria pertaining to reading requirements for the QOL assessments (Figure 1).

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Figure 1.—Patients qualifying for the clinical trial (n = 594) and quality-of-life (QOL) assessment (n = 569) were randomized to placebo or active therapy with glipizide gastrointestinal therapeutic system (GITS). The study flow is shown for QOL and health economic assessment. Of the 594 patients followed up clinically, 67 patients withdrew prematurely, 30 from the placebo group and 37 from the glipizide GITS group. Most withdrew for medical reasons (21), including those having symptoms of hyperglycemia (placebo, 4; glipizide GITS, 1), hypoglycemia (glipizide GITS, 3), too high hemoglobin A1clevels (placebo, 5), too high fasting plasma glucose levels (placebo, 2), too high home fasting blood glucose levels (FBG) (placebo, 3), too low home FBG levels (glipizide GITS, 1), and too low clinic FBG levels (glipizide GITS, 1; placebo, 1). Other reasons included having adverse experiences (AEs) (16), protocol violations (17), and 3 patients lost to follow-up (LTF). Ten withdrew because of "other" administrative reasons.
Statistical Methods

We used factor analysis to identify symptom clusters and to calculate the QOL global outcome score. We used multivariate and univariate analyses of variance (ANOVAs) and covariance to assess the differences between the placebo and active therapy groups with regard to changes in the QOL scales, subscale, and diary symptom scores. We used general linear models to evaluate the relationship between changes in glycemic control and changes in QOL, health resource use, work, and disability days. Exact statistical tests on proportions and incidence rate ratios were used to compare the probability of work loss, absenteeism, bed-days, and disability-days. Logit models were used to compare the difference in the rate of change between baseline and end point for these variables. Means (±SEs) are reported unless specified otherwise. All QOL and clinical changes were computed from baseline to end point (last value carried forward) based on intent-to-treat analysis.

Quality-of-life treatment differences are reported in SD of change (responsiveness) units during stable treatment (calculated using weeks 11 and 15). This metric of change has been previously calibrated to negative life events.20 The statistical power of 0.80 was based on detecting greater than a 0.24 SD difference between placebo and glipizide GITS in the QOL change score (2-tailed statistical test, α=.05). To maximize benefit to the active therapy group and minimize exposure to placebo while maintaining adequate power, 2 patients were randomized to glipizide GITS for each patient randomized to placebo. Significance levels were unadjusted for multiple comparisons and were all based on 2-tailed tests of significance. Randomization was performed according to a computer-generated code (balanced in blocks of 4) prepared prior to the start of the study by the manufacturer of glipizide GITS and the placebo pills.

Demographic and Clinical Evaluations

Demographic, clinical, and QOL characteristics at baseline are reported in Table 1. Essential hypertension (47%), dyslipidemia (27%), and osteoarthritis or unspecified arthritic disorders (17%) were the most common concomitant illnesses. Concomitant medications included antihypertensive drugs (39%), drugs for rheumatic diseases and gout (35%), antibacterial drugs (21%), diuretics (17%), and lipid-lowering agents (15%). Seventy-nine percent of patients had been taking oral hypoglycemic therapy previously. There were no significant differences in the baseline characteristics of the participants placed in either of the 2 randomized groups.

Table Graphic Jump LocationTable 1.—Demographic, Clinical, and Quality-of-Life Characteristics at Baseline (N = 569)*

The percentages of patients titrated to a final dose of 5 mg, 10 mg, 15 mg, and 20 mg by the end of the study were 4.5%, 5.8%, 5.8%, and 84.2% for placebo and 23.8%, 15.4%, 12.1%, and 48.6% for glipizide GITS, respectively. In the glipizide GITS group, HbA1c and fasting blood glucose levels exhibited significant decreases from baseline to week 15 of 0.9%±0.1% and 2.4 ± 0.2 mmol/L (43 ± 3 mg/dL), respectively (P<.001), while the placebo group increased by 0.7%±0.1% (P<.001) and 0.1±0.2 mmol/L (1±4 mg/dL) (P=.76), resulting in statistically significant differences in glycemic control between groups (P<.001). At the end of the study (week 15), HbA1c and fasting blood glucose levels for active therapy (glipizide GITS) vs placebo were 7.5%±0.1% vs 9.3%±0.1% and 7.0±0.1 mmol/L (126±2 mg/dL) vs 9.3±0.2 mmol/L (168±4 mg/dL), respectively (P<.001).

Self-reported Monitoring

During the final week, 7 (4.8%) of 146 patients in the placebo group and 19 (6.0%) of 316 patients in the glipizide GITS group reported symptoms of hypoglycemia (P=.67) in their diaries; however, none had a corresponding blood glucose level less than 3.1 mmol/L (55 mg/dL). During the same week, the 43-item symptom diaries showed more favorable changes from baseline for patients taking glipizide GITS compared with those taking placebo for frequency of urination (P=.048), blurred vision (P=.049), the hyperglycemia composite symptom scale (P=.05), and all 3 cognitive functioning scales (P=.007) (difficulty concentrating [P=.05], inability to think clearly [P=.009], difficulty remembering [P =.006]). Treatment difference effect sizes (responsiveness SD units) ranged from +0.37 to +0.56 in favor of active therapy. There were no significant differences between the 2 groups in the hypoglycemic symptom scale, which included breathing hard, fast pulse, pounding heart, sweating, feeling tense, trembling, and feeling lightheaded and weak (P=.60). Similar results were obtained for interim study weeks 7 and 11.

Clinic-Based QOL Questionnaires

The 5 major QOL scales showed more favorable changes for glipizide GITS–treated patients (P=.008, multivariate ANOVA) with significant treatment differences ranging from +0.16 to +0.59 responsiveness SD units (Figure 2). Treatment differences for symptom distress (+0.59; P<.001), general perceived health (+0.36; P=.004), cognitive functioning (+0.34; P=.005), and overall VAS ratings (+0.24; P=.04) were more favorable for the active therapy arm than the placebo arm. Although the direction of the treatment difference for the mental and emotional health scale favored the active therapy arm (+0.16; P =.22), the difference did not reach statistical significance. The associated subscales all favored the active therapy arm with significant treatment differences or trends for cognitive acuity and memory (+0.38; P=.002), VAS emotional rating (+0.35; P=.003), general health (+0.27; P=.01), sleep (+0.26; P =.04), depression (+0.25; P =.05), disorientation and detachment (+0.23; P=.045), vitality (+0.22; P=.04), and VAS physical rating (+0.19; P=.09).

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Figure 2.—Mean changes from baseline to week 15 for the global scales of quality-of-life for patients randomized to diet and placebo or diet and glipizide gastrointestinal therapeutic system (GITS). Asterisk indicates P<.05; dagger, P <.01; and double dagger, P<.001.

As shown in Table 2, the more favorable QOL outcomes for glipizide GITS were mediated largely by the reduction in symptom distress associated with the symptoms of hyperglycemia. In contrast, hypoglycemic symptoms, although favoring placebo, were not significantly different between groups.

Table Graphic Jump LocationTable 2.—Baseline to End Point Treatment Differences in Symptom Distress Between Placebo and Glipizide Gastrointestinal Therapeutic System (GITS)

As depicted in Figure 3, using data from both groups, the QOL global outcome change score between baseline and week 15 was calibrated against the interval change in HbA1c levels. Relative to other studies19,20,25 using similar QOL scales, the calibration showed that increases in HbA1c levels of 1.0% or greater are associated with substantial decrements in QOL, while decreases of the same magnitude showed smaller, but clinically important, improvements in QOL. Patients taking active therapy improved significantly more than patients taking placebo after controlling for the degree of worsening or improvement in HbA1c levels using analysis of covariance (P=.03). For the group as a whole, improvements in the QOL summary score were correlated with fewer bed-days (P=.02), fewer days of restricted activity (P<.001) and limitations in activities (P=.006), and a decreased amount of health care services use (P=.01).

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Figure 3.—Calibration of baseline to week 15 change in the quality-of-life (QOL) global outcome factor scores to change in hemoglobin A1c(HbA1c) expressed as 5 categories. Coordinates shown are mean (±SE) QOL change scores within each HbA1c change category with corresponding log-linear fitted function for the 5 mean coordinates (P<.001). Full regression sum of squares for QOL changes as a function of actual change in HbA1c was statistically significant at P =.008.

To address whether the decreases in QOL were driven mostly by the somatic effects of symptoms rather than psychological factors such as frustration due to persistent hyperglycemia despite "taking medication," responses to the 3 items focusing on "worries, concerns, and fears about health," "feelings of anxiety and frustration," and "strain, stress, and pressure" were analyzed separately. Results indicated that both groups improved on all items as the study progressed with no differences in the degree of improvement. The mental health scale also showed no deterioration for the placebo group as depicted previously in Figure 2.

Employment, Work Loss, Bed-Days, and Days of Restricted Activity

As shown in Table 3, baseline rates of employment, group productive capacity, health-related absenteeism, bed-days, and days of restricted activity were similar for the 2 groups. By week 15, improved glycemic control for patients in the active therapy group was associated with greater improvement in overall work and disability outcomes compared with patients in the placebo group. Active therapy patients experienced higher retention of employment (97% vs 85%) and a greater retained productive capacity (99% vs 87%) compared with the placebo group, even beyond what could be attributed simply to the difference in the dropout rate. Changes in absenteeism, bed-days, and days of restricted activity also were statistically different between the 2 groups. By week 15, absenteeism rose 8.1% for the placebo group and decreased slightly by 0.8% for the active therapy group. The absenteeism risk ratio (missed work cases per person-days worked) was 4.8 (95% confidence interval, 2.0-11.9), indicating a nearly 5-fold increase in risk of absenteeism for placebo vs active therapy. The number of patients reporting that they stayed in bed for a half day or more per week rose 4.4% for the placebo group but slightly declined 0.4% for the active therapy group. Rates of bed-days and days of restricted activity (half day or more) were both more favorable for active therapy group. These differences resulted in higher estimated production losses for the placebo group compared with active therapy group (Table 4).

Table Graphic Jump LocationTable 3.—Health Economic Indices at Baseline and Week 15 for Placebo and Glipizide Gastrointestinal Therapeutic System (GITS)
Table Graphic Jump LocationTable 4.—Estimated Production Losses at Baseline and Week 15 for Placebo and Glipizide Gastrointestinal Therapeutic System (GITS)
Health Care Use

The rate of hospitalizations was low at baseline and throughout the treatment period (0.08 days per person) and was comparable between the 2 groups. Home nurse visits were used by less than 1% of both groups, while use of general household assistance was reportedly used by 7.8% of those in the placebo group and 4.9% of those in the active therapy group during the last 4 weeks of treatment (P=.22). The number of patients reporting 1 or more nonstudy ambulatory care visits (clinic, emergency department, or physician office) were comparable at baseline but decreased more by week 15 for patients taking glipizide GITS (38.9% to 27.7%; P =.002) compared with placebo (36.7% to 34.0%; P=.65), yielding an estimated savings of $11 per patient per month assuming a cost of $66 an ambulatory visit. A summative index of health care use correlated negatively with the change in the QOL global outcome score (P=.01), so as QOL improved with better glycemic control, overall health care use decreased.

Although many studies have focused on the long-term benefits of glycemic control in reducing diabetic complications, this study demonstrated the shorter-term symptomatic relief, improvements in QOL, and health economic benefits associated with improved glycemic control in patients with type 2 DM. The QOL improvements were both consistent and substantial across all major domains and were due, in part, to the reduction in adverse symptoms associated with hyperglycemia with no measurable increase in hypoglycemia or its associated symptoms.

The power of this study to detect a strong relationship between glycemic control and QOL while other studies have not1,812 is probably due to a number of factors, including a low incidence of hypoglycemia, which would not offset gains in QOL from improved glycemic control; longitudinal evaluations, which guard against the confounding typical in cross-sectional studies; a placebo-control group with substantial hyperglycemia; and comprehensive disease-specific evaluations focusing on patient self-perceptions of symptoms and health.

In contrast to previous studies of type 1 DM,1,11 diary reports of perceived hypoglycemia and associated autonomic symptoms were relatively uncommon and not significantly different between the 2 arms. However, patients in the placebo group reported significantly more distress with hyperglycemia-related symptoms than patients receiving glipizide GITS. The diary results suggest that using a reporting period as brief as 24 hours, treatment differences favoring patients in good control are evident. More substantiating evidence was obtained from the clinic assessments that showed that improved glycemic control was associated with improvements in all QOL domains with only 1 scale, mental and emotional health, not quite reaching statistical significance.

The largest and most dramatic treatment difference occurred in the symptom distress index and the symptom clusters commonly related to hyperglycemia, as well as other nonspecific symptoms. Although a cluster of symptoms commonly associated with hypoglycemia was detected, the treatment difference was much smaller and not statistically different between groups.

The other consistent finding was the improvement in perceived cognitive function with improved glycemic control. Loss of cognitive ability is feared by patients with diabetes as one of the potential negative symptoms of hypoglycemia often associated with tighter glucose control. Paradoxically, cognitive functioning showed a much more beneficial profile for patients randomized to the sulfonylurea glipizide GITS than placebo.

We also observed a strong relationship between improved glycemic control and the beneficial changes in QOL, suggesting that the rate of QOL deterioration due to increasing symptoms is progressive with worsening glycemic control. This relationship also supports the hypothesis that it is the relief from negative symptoms of hyperglycemia that facilitates the improvement in QOL seen herein. However, the finding that glucose lowering alone could not account entirely for the more beneficial QOL profile observed for patients taking glipizide GITS suggests that other factors, eg, smaller daily fluctuations in blood glucose levels, may also be involved.

That subjects were not blinded to their home blood glucose readings may have contributed to the associations observed. However, the symptom distress index was highly sensitive and specific for identifying the most relevant disease-specific effects of glycemic control to an extent that cannot be solely attributed to knowledge of glucose levels (Table 2). In addition, even though fasting blood glucose levels were identical from baseline to end point for the control group, their corresponding QOL scores declined substantially, indicating that individuals were reporting deterioration in QOL even with the knowledge of constant blood glucose readings. This further suggests that the negative effects of poor control might be cumulative and progressive.

Previous studies have demonstrated that treatment differences greater than 0.10 to 0.15 SD units or more are clinically meaningful.20,25 Twenty-three symptoms evaluated by the symptom distress index showed treatment differences favoring the glipizide GITS group of 0.2 SD units or greater compared with the placebo group (Table 2). The treatment difference for the global symptom distress scale was 0.59 SD units and for cognitive function and perceived health status was approximately 0.35 SD units. For comparison purposes, patients who undergo hip arthroplasty typically improve between 0.32 and 0.47 SD units, depending on the QOL scale used.26

When evaluating the cost-effectiveness of therapeutic and management programs, it is important to consider that the changes in QOL found herein were significantly correlated with use of medical and health care services as well as work days lost, sick days, and days of reduced activities. Furthermore, improved glycemic control positively affected employment, absenteeism, productive capacity, bed-days, and days of restricted activity in addition to ambulatory medical services. The direct and indirect costs associated with the observed treatment differences could be considered substantial relative to the typical capitation allotments for the patient with type 2 DM. However, these savings must be balanced against the increased costs of improved glycemic control, such as medication and home glucose monitoring supplies.

The usual methods of evaluating the economic benefits of diabetes treatment typically focus on lifetime costs and savings using Monte Carlo simulations and decision analytic modeling techniques.12,27,28 Assuming that the treatment differences observed in this clinical trial could be maintained throughout the lifetime of this cohort, long-term health and economic benefits might indeed be substantial. However, patients, employers, and health care providers might be more motivated to implement and comply with education and disease management programs if immediate QOL and health economic benefits could be anticipated.

When assessing the benefit of therapies and disease management programs for formularies and managed care organizations, emphasis should be placed on the patient's health perceptions and QOL in addition to the more common measures of objective health status and process-oriented or report card criteria (eg, convenience, waiting time, and number of laboratory tests and special tests performed). Health perceptions may be a more sensitive reflection of overall patient satisfaction with health care services than such process-oriented measures. For the patient with type 2 DM, even a moderate worsening in HbA1c levels was shown to affect negatively the patient's QOL and overall well-being. For the payer, the lost productivity, increased absenteeism, and increased use of health resources associated with poor glycemic control should provide a strong incentive for demanding more comprehensive diabetes management from the health care provider organization than what is currently offered. We conclude from our findings that the day-to-day QOL in patients with type 2 DM can be enhanced by better glucose control and should be considered when implementing disease management programs, evaluating health outcomes and patient satisfaction, and estimating the costs and benefits of therapeutic regimens and prevention programs.

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Figures

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Figure 1.—Patients qualifying for the clinical trial (n = 594) and quality-of-life (QOL) assessment (n = 569) were randomized to placebo or active therapy with glipizide gastrointestinal therapeutic system (GITS). The study flow is shown for QOL and health economic assessment. Of the 594 patients followed up clinically, 67 patients withdrew prematurely, 30 from the placebo group and 37 from the glipizide GITS group. Most withdrew for medical reasons (21), including those having symptoms of hyperglycemia (placebo, 4; glipizide GITS, 1), hypoglycemia (glipizide GITS, 3), too high hemoglobin A1clevels (placebo, 5), too high fasting plasma glucose levels (placebo, 2), too high home fasting blood glucose levels (FBG) (placebo, 3), too low home FBG levels (glipizide GITS, 1), and too low clinic FBG levels (glipizide GITS, 1; placebo, 1). Other reasons included having adverse experiences (AEs) (16), protocol violations (17), and 3 patients lost to follow-up (LTF). Ten withdrew because of "other" administrative reasons.
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Figure 2.—Mean changes from baseline to week 15 for the global scales of quality-of-life for patients randomized to diet and placebo or diet and glipizide gastrointestinal therapeutic system (GITS). Asterisk indicates P<.05; dagger, P <.01; and double dagger, P<.001.
Graphic Jump Location
Figure 3.—Calibration of baseline to week 15 change in the quality-of-life (QOL) global outcome factor scores to change in hemoglobin A1c(HbA1c) expressed as 5 categories. Coordinates shown are mean (±SE) QOL change scores within each HbA1c change category with corresponding log-linear fitted function for the 5 mean coordinates (P<.001). Full regression sum of squares for QOL changes as a function of actual change in HbA1c was statistically significant at P =.008.

Tables

Table Graphic Jump LocationTable 1.—Demographic, Clinical, and Quality-of-Life Characteristics at Baseline (N = 569)*
Table Graphic Jump LocationTable 2.—Baseline to End Point Treatment Differences in Symptom Distress Between Placebo and Glipizide Gastrointestinal Therapeutic System (GITS)
Table Graphic Jump LocationTable 3.—Health Economic Indices at Baseline and Week 15 for Placebo and Glipizide Gastrointestinal Therapeutic System (GITS)
Table Graphic Jump LocationTable 4.—Estimated Production Losses at Baseline and Week 15 for Placebo and Glipizide Gastrointestinal Therapeutic System (GITS)

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