In 1992, diabetics made up only 4.5% of the U.S. population,

Transcription

1 RESEARCH Implementation and Evaluation of a Pharmacist-managed Diabetes Service OBJECTIVE: To evaluate the impact of a pharmacist-managed diabetes service on changes in hemoglobin A1C (HbA,,), RESULTS: At the end of the study the mean :l:sd HbA" was 7.5 :I: 1.2% (95% CI, %) for the intervention by Charlie Kelly and Philip T Rodgers i blood pressure, lipids, and smoking sta- tus in diabetic patients. DESIGN: A prospective analysis of the outcomes of a pharmacist-managed dia- betes referral service compared to out- comes of standard medical care provid- ed by physicians in a cal control. matched histori- SETTING: Richmond Health Care Group, a managed care-affiliated physicians group in Virginia. PATIENTS: 16 type 2 diabetics in the his- torical control group; and 26 type 2 and 6 type 1 diabetics in the intervention group with a HbA" value greater than 8%, or a documented elevated systolic (over 130 mm Hg) or diastolic (over 85 mm Hg) blood pressure, or elevated lowdensity lipoprotein (LDL) cholesterol level that was 120% of goal or more. INTERVENTIONS: Patients in the inter- vention group received dosage adjust- ments, diabetes self-management train- ing, and periodic assessment of treat- ment goals by pharmacists. group and 8.5 :I: 1.4% (95% CI, 7.8&- 9.20%) for the historical control group, 11=0.02. There was no statistical difference in SBP and DBP between the two groups, although there was a trend toward a lower SBP in the intervention group (mean:l: SD SBP 133.5:1: 17.9 mm Hg; 95% CI, mm Hg) com- pared with the historical control group (mean :I: SD SBP :I: 14.9 mm Hg; 95% CI, mm Hg), 11=0.22. There was no difference between baseline (mean :I: SD LDL :I: 39.8 mg/dl; 95% CI, mg/dl) and follow-up LDL (mean :I: SD LDL :I: 30.6 mg/dl; 95% CI, mg/dl) by within-group analysis, 11=0.82. CONCLUSION: A pharmacist-managed diabetes service was effective in reduc- ing HbA" values in diabetic patients. This study demonstrates the positive impact of clinical pharmacists in achieving a pri- mary therapeutic goal in diabetic patients for overall diabetes control and possibly blood pressure. KEYWORDS: Type 2 diabetes, primary care, pharmacists, hemoglobin A", smoking cessation In 1992, diabetics made up only 4.5% of the U.S. population, but accounted for more than 14.6% of total health' care expenditures, or approximately $105 billion. I The major costs are attributed to the significant morbidity and mortality intrinsic to this disease. For instance, diabetes has been implicated as the major cause of microvascular complications, causing 12% of all new cases of blindness, almost half of nontraumatic lower-extremity amputations, and over one-third of new cases of end-stage renal disease.2 In addition, macrovascular complications lead to substantial morbidity and mortality. Diabetics are two to four times more likely to die from heart disease or suffer a disabling stroke than nondiabetics2 Micro- and macrovascular diseases associated with diabetes can be prevented by correcting glucose, blood pressure, and lipids with proper screening and monitoring, even in type 2 diabetics]'s Several studies have documented a positive impact for clinical pharmacists on improving outcomes'. in diabetic patients6.8 Furthermore, other studies have shown positive effects of pharmacy services on costs and outcomes associated with the management of other diseases9.!] We sought to implement a pharmacist-managed diabetes. service aimed at preventing diabetic complications through appropriate disease management2 The objective of our study was to evaluate the impact of this service on changes in critical endpoints known to cause significant rriorbidity and mortality MAIN OUTCOME MEASURES: HbA,c, systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL, and smoking J Managed Care Pharm 2000: in diabetic patients. Methods cessation. A computer database search of pharmacy claims identified dia- betic patients taking oral. diabetic agents or insulin from January 1998-July Patients were sorted by ten physician providers. Each primary care provider received this list of patients for review, along with instructions to select patients from the list for enrollment in the clinical pharmacy service; all of the providers believed that their patients would benefit from comprehensive pharmacological treatment review and titration and diabetes self-management training provided by clinical pharmacists. The clinic site included one full-time clinical pharmacist/faculty member, one pharmacy resident, and fourth-year Doctor of Pharmacy students from the local School of Pharmacy 14 Study Subjects Patients selected from the referral pool were included for study 488 Journal of Managed Care Pharmacy jmcp NovemberlDecember 2000 Vol. 6, No.6

2 , Im~lementation and Evaluation of a Pharmacist-managed Diabetes Service if they had a documented glycosylated hemoglobin (HbAk) value that was higher than 8%, a documented elevated systolic (over 130 mm Hg) or diastolic blood (over 85 mm Hg) pressure, or a low-density lipoprotein (LDL) cholesterol level that was 120% of,goal or more, Baseline values for HbAk, blood pressure, and LDL were col- lected at the initial visit, if they had not been obtained within the previous three months, Otherwise, an HbA" value documented within a prior three-month period or an LDL collected within a prior year's period was allowed to qualify as the baseline value, Patients without a follow-up consultation with a pharmacist were excluded from the study. Interventions During the initial visit the pharmacist provided one-on-one assessments and consultations regarding diabetes self-manage- ment. A complete medical history and appropriate laboratory values (HbAk, fasting lipid profile, urinalysis, and thyroid func- tion tests) were obtained if indicated. The patient and pharma- cist worked together to design a management plan to establish short- and long-term goals, assess medication issues (including dosage adjustments in collaboration with the providers), and individualize nutrition recommendations, lifestyle changes (diet, exercise, smoking cessation), and blood-glucose monitoring instructions. Annual dilated-eye exams, consultation for podiatry services, agreement on continuing support from the clinical pharmacist, follow-up, and instructions on how to contact the physician or pharmacist in the case of an acute problem were also discussed. Follow-up was scheduled based on the degree of monitoring required, usually monthly. In addition, patients received continu- ing education on self-management topics including appropriate diet, weight control, daily foot care, medication compliance, and self monitoring of blood glucose (SMBG). Pharmacists implemented a diabetes continuing-care monitoring 'sheet to track the delivery of appropriate care, such as referrals for dilated-eye exams and foot care, and timely acquisition of fasting lipoprotein analysis, urinalysis, and HbAk levels. We used the 1997 American Diabetes Association's clinical practice recommendations regard- ing goals of therapy. Interventions were customized based on the patient's individual goals. 15 Surveillance and FOllow-up Patients were monitored according to the 1997 American Diabetes Association's clinical practice recommendations as described above. Planned contact frequency was weekly for the initiation of insulin or a change in insulin regimen, biweekly for initiation of oral glucose-lowering agents or change in an oral regimen, biweekly for patients who were not meeting goals, and every two to three months for well-controlled patients. Laboratory evaluation of HbAk was obtained quarterly if treatment had changed or the patient was not meeting goals, or every six months if the patient remained stable. A fasting lipid profile, a urinalysis for protein, and a comprehensive dilated eye and visual exam were planned on an annual basis. Self-management plan evaluation at each visit included review of the patient's short- and long-term goals, medications, frequen- cy and severity of hypoglycemia, 5MBG results, control of lipids, blood pressure, and weight. Also reviewed and discussed were the patient's medical nutrition therapy (MNT), exercise regimen, follow-up for referrals, and psychosocial adjustment. Goals of treatment, unless contraindicated, included achievement of near normoglycemia (fasting blood glucose mgldl; bedtime blood glucose mgldl; HbAlc lower than 7%); lowering of blood pressure to less than 130/85 mm Hg or to below 125/75 mm Hg for patients with proteinuria of greater than 19m/24 hours; and LDL less than 130 mgldl for patients with two or more cardiovascular risk factors, or 100mgldL or less for patients with established cardiovascular, cerebrovascular, or peripheral vascular disease. 15 The LDL goal for all intervention patients was adjusted to 100 mgldl or less based on the changes made by the 1999 American Diabetes Association's Clinical Practice Recommendations released at the time of this study. 16 HbAk values and blood pressures were measured at baseline and at the end of the study period seven months later, then compared to values collected from historical controls over an equivalent period. Lipids were assessed at baseline and compared nine months later, then compared to values collected from historical controls over an equivalent period. A collection period of nine months was used to increase the number of lipid values available for analysis. The 1997 American Diabetes Association's Clinical Practice Recommendations suggest an annual assessment of lipids for most patients. Within-group analysis for smoking status was assessed at the end of the sevenmonth period. Intention-to-treat analysis used the last available laboratory parameter carried forward. Historical Controls Sixteen historical controls (100% type 2 diabetics) were randomly selected from the referral list and studied retrospectively over an equivalent nine-month period, but one year prior to ini- tiation of the clinical service. These patients were matched for baseline age, BMI, HbAk, SBp' DBP, LDL, HDL, and TG levels (see Table 1, page 490). There were no type 1 diabetes in the historical control group because of the relative infrequency of this type of diabetic in clinical practice compared to type 2 dia- betes, making identification of this subset difficult. Statistical Analysis For HbAlc, a sample size of seven patients in each arm would have 80% power (p=0.05) to detect a difference in HbAk of two absolute percentage points between the intervention group and the historical control group if the standard deviation was 1.3% Vol. 6, No, 6 NovemberlDecember 2000 jmcp Journal of Managed Care Pharmacy 489

3 1Ir.1.:.I:J=- -- Baseline Líf'''I:~~~l'W t~llit0fi?d"'m-'fl'.r Characteristics of the Subjects Characteristics I Historical Controls (N=16) Intervention Group (N=32) P Values' Age (years) 50.2 :t :tl Female sex (%) Male sex (%) BMI (kg/m2) 33.5 :t :t Type I DM (%) Type 2 DM (%) HbA\c (%) 9.0 :to :t Systolic blood pressure (mm Hg) :t :t Diastolic blood pressure (mm Hg) 87.3 :t :tll LDL (mg/dl) ll9.7 :t :t HDL (mg/dl) 40.4 :tll :t TG (mg/dl) :ti :t Smokers (%) Note: Plus-minus values are means :t SD. Percentages do not all sum to 100 because of rounding. "A chi-square test was used for comparisons of categorical variables, and a two-tailed student's t-test was used for comparisons of continuous data....:t:t.=-- IIIBill." ^~.'^ Comparison of Endpoints Analyzed by Group Analysis Characteristic Historical Controls Intervention Group P Values HbAlc (%) 8.5 :tl :tl ( ) ( ) Systolic blood pressure (mm Hg) :t :t ( ) ( ) Diastolic blood pressure (mm Hg) 82.6 :tl :tlo.7 ( ) ( ) 0.58 Note: Plus-minus values are means :t SO (95% confidence intervals). Percentages do not all sum to 100 because of rounding. for both groups. For SBp, a sample size of 12 patients in each arm would have 80% power Cp=0.05) to detect a difference in SBP of 26 mm Hg between the intervention group and the historical control group if the standard deviation was 22.9 mm Hg for both groups. For DBP, a sample size of nine patients in each arm would have 80% power Cp=0.05) to detect a difference in DBP of 17 mm Hg between the intervention group and the his- torical control group if the standard deviation was 12.5 mm Hg for both groups. For LDL, a sample size of 28 in each arm would have 80% power Cp=0.05) to detect a difference in LDL of 30 mgldl between the intervention group and the historical control group if the standard deviation was 39.8 mgldl for both groups. For analysis, 32 intervention patients were available, and 16 for the historical control sample, which was half the size of the inter- vention group; this fact led to the understanding that we might not be able to detect a difference in LDL between the two groups. Results are based on within-group analyses for changes in LDL and s~oking cessation rates and between-group analyses for changes 490 Journal of Managed Care Pharmacy jmcp NovemberlDecember 2000 Vol 6, No.6

4 in HbAlc, SBp, and DBP A paired student's t-test was used to compare baseline continuous values in the intervention group to the follow-up values within the same group. An unpaired student's t- test was used for comparisons of continuous data between the intervention group and the historical controls. Chi-square analysis was used to compare proportions. A two-tailed p-value of less than 0.05 was considered statistically significant. Percent of Patients at the End of the Study with Laboratory Values at Goal according to the 1997 American Diabetes Association Clinical Practice Recommendations Results Baseline characteristics of the intervention group are presented in Table 1 (see page 490). Oflhe 32 intervention patients avail- able for study, 27 had available HgAlc values for analysis at the end of the seven-month period. Five patients in the intervention group were lost to follow-up; one patient changed insurance plans and the remaining four did not keep appointments. The mean:t SD HbAlc at baseline was 9.0 :t1.3% for the intervention group and 9.0 :to.74% for the control group; p=0.84. The mean.:tsd HbAlc at the end of the study was 7.5 :t1.2% (95% cr, %) for the intervention group and 8.5 :t1.4% (95% cr, %) for the historical control group, p=0.02 (see Table 2, page 490). Thirty-one percent 00/32) of the interven- tion group and 6.3% (116) of the control group had HgAlc values less than 7% at the end of the study period; p=0.03. By intention-to-treat analysis, the follow-up mean :tsd HbAlc was 7.9 :t1.4 (95% cr, %) for the intervention group and 8.5 :t1.4 % (95% cr, %) for the control group; p=0.12. This difference was not significant but there was a trend toward a lower mean HbAlc in the intervention group. No statistical difference was found for SBP and DBP between the two groups (Table 2), although the proportion of patients with SBP lower than 130 mm Hg was higher in the intervention group, with 43.8% 04/32) for the intervention group and 12.5% (2/16) for the historical control group; p=o.01. The proportion of patients with DBP lower than 85 mm Hg was higher in the intervention group, with 65.6% (21/32) for the interven- tion group and 62.5% (0116) for the historical control group; p=0.78 (see Figure 1, right). There was no difference between baseline (mean :tsd LDL :t39.8 mg/dl; 95% cr, mg/dl) and follow-up LDL (mean :tsd LDL 121.2' :t30.6 mg/dl; 95% cr, mg/dl) by within group analysis, p=0.82. By intention-to-treat analysis, the follow-up mean :tsd LDL was :t34.8 (95% cr, mg/dl) by within-group analysis for the intervention group;p=o.21. None of the eight smokers in the intervention group successfully quit smoking despite intervention; p=1.0. Limitations. Selection bias by the providers toward effective pharmacist performance is possible; otherwise referrals would have been opposed. AdditionaÏly, small sample sizes in both study groups could have affected the power of the study to observe true differences between them. Specifically, the absolute difference in HgAi<<7% p=o.03 SBPd30 mm Hg p=ool DBP<85 mm Hg p=o.78 o SBP between the study groups was too small to reach statistical significance, despite a 6.6 mm Hg lower SBP in the intervention group (Table 2). The study was powered to detect a difference of no less than 26 mm Hg between the two groups. The absolute reductions in DBP and LDL were clinically insignifi- cant, possibly because baseline values for DBP and LDL were already close to goal in both groups (Table 1). Discussion With the pharmacist-managed diabetes service in this employed physicians group, we were able to demonstrate a significant improvement in the HgAlc, which is recognized as an important short -term parameter associated with long-term outcomes We were able to demonstrate this difference in the relatively short period of seven months. The absolute difference reduction of HgAlc of 1.5% in our study is similar to that found in other trials to benefit microvascular complications.18 If the service could be continued, we would strive to maintain glycemic control, attract more diabetic patients, and measure more health- resource use parameters, but the short duration of this initial study did not allow for these analyses. Although we did not find significant differences in SBP and DBP between the intervention group and the historical control group, a trend toward lower blood pressures was observed in the intervention group, especially in SBP (Table 2). The small number of subjects may have made it impossible to detect the small differences in blood pressures found. For SBp, a sample size of 98 in each arm would have been necessary to detect sig- nificance. Similarly, for DBp, a sample size of 561 in each arm Vol. 6, No.6 NovemberlDecember 2000 jmcp Journal of Managed Care Pharmacy 491

5 \ I.' would have been necessary. If more subjects had been employed, we might have been able to demonstrate a difference in blood pressure. Comparisons of LDL between the intervention group and the historical control grqup were not possible, given the revisions made during the time of this study for the management of dyslipidemia in adults.16 LDL-cholesterol goals for diabetic patients without preexisting CHD were revised to reflect an LDL goal of 100 mg/dl or lower compared to a less stringent LDL goal that reflected the number of coronary heart disease risk fac- tors present.is.16 Because the intervention-group LDL goal was now different from the LDL goal for the historical control group and because our interventions were goal-driven, we chose to compare baseline LDL to follow-up LDL within the intervention group and not utilize the historical control group for compari- son of this parameter between groups. Although no statistical difference (p=0.82) between baseline LDL and follow-up LDL was revealed by within-group analysis, a small trend in LDL reduction was observed (baseline mean :tsd LDL :t39.8 mg/dl and follow-up mean :tsd LDL :t30.6 mg/dl). Withonly ten LDL levels available at the end of the study, we may not have had the power to detect such a small difference. The number of evaluable LDL levels is low because we utilized a relatively short collection period for lipids, to avoid increasing the number of laboratory evaluations of lipids beyond the recommended yearly fasting lipid collec- tion recommended in the 1997 American Diabetes Clinical Practice Recommendations. IS Clearly, a longer study period. would have captured more lipid values, and perhaps we may have reached statistical significance. By intention-to-treat analysis, the follow-up mean :tsd LBL was :t34.8 (95% 0, mg/dl) compared to baseline (mean :tsd LDL :t39.8 mg/dl; 95% 0, mg/dl), p=0.21. When utilizing the last evaluable LDL level carried forward, we see a stronger trend but still without statistical significance. We were surprised to find aspirin use so low in our study (9.4% at baseline). This was not an a priori endpoint in our study and therefore the mechanisms utilized to detect aspirin use at baseline and follow-up were not optimal, although some interpretation of these results can be made. ADA guidelines advise aspirin use in all diabetic patients without contraindica- tions. IS We were pleased to find an improvement in the number of patients taking aspirin over the course of the study. HMG CoA reductase inhibitor use did increase as a result of our study but did not result in a significant reduction in follow-up LDL levels. This may again be a result of the low number of evalu- able LDL levels available at follow-up. Certain critical parameters should be focused on and optimized in the diabetic population. Large clinical studies have established the benefits of tight control of glucose in reducing the risk of microvascular complications in diabetic patients Journal of Managed Care Pharmacy jmcp November/December 2000 The Diabetes Control and Complications Trial (DCCT) demonstrated that tight glycemic control in type 1 diabetics signifi- cantly prevents the onset or development of retinopathy, nephropathy, and neuropathy. Evidence also supports the benefits of tight control in type 2 diabetics. Results from the United Kingdom Prospective Diabetes Study-33 (UKPDS 33) revealed a 25% risk reduction in microvascular endpoints, mostly due to a reduction in retinopathy, in tightly controlled patients with type 2 diabetes mellitus. 18 Controlling blood pressure is also critical in diabetic patients. Hypertension increases the risk of cardiovascular dis- ease, microalbuminuria, and retinopathy in type 2 diabetics.192s Lowering of blood pressure benefits both type 1 and type 2 dia- betics. Lower blood pressure reduces albuminuria both in type 1 and in type 2 diabetics and slows the deterioration of renal function in type 1 diabetics An analysis from the UKPDS 38 trial of type 2 diabetic patients with hypertension utilizing either captopril or atenolol as the main treatment revealed a 24%,32%,44%,56%, and 37% risk reduction in diabetes related endpoints, deaths related to diabetes, strokes, heart failure, and microvascular endpoints, respectively, over a median fol- low-up of 8.4 years with tight control (144/82 mm Hg) compared to less tight control (154/87 mm Hg).29 The Hypertension Optimal Treatment (HOT) study demonstrated a 51 % reduction in major cardiovascular events in the group with target diastolic blood pressure 80 mm Hg or lower compared with 90 mm Hg or lower in patients with diabetes 30 Subgroup analyses of diabetic patients in clinical studies have also demonstrated substantial benefit of LDL lowering in 32 diabetic patients with coronary artery disease31. Recently, results from UKPDS 33 revealed a 25% risk reduction in microvascular endpoints over ten years in 3,867 newly diag- nosed type 2 diabetics who received treatment with either a sulphonylurea or insulin versus patients who received conventional treatment with diet.'s An 11 % reduction in HbAlc (7.0% in the intensive group compared with 7.9% in the conventional group) was noted, compared to an 11.8% reduction in HbAlc (7.5% in the intervention group compared with 8.5% in the historical control group) found in our study (Table 2). A similar reduction in microvascular endpoints over ten years might be expected in our study population if this reduction persisted, given continued pharmacy services. Two similar studies utilizing pharmacists to deliver educa- tion, medication counseling and adjustment, and monitoring have shown significant improvements in glycemic control in type 2 diabetic patients 6. 7 Although only one study utilized a control group, both studies were able to reduce HbAlc values by greater than two absolute percentage points with both studies reaching statistical significance as well. These two studies corroborate the results from our study, showing the positive effects of a pharmacist-managed programs on outcomes in diabetic patients. Vol. 6, No.6

6 Conclusions A pharmacist-managed continuing care service is effective in reducing HbAlo values and increasing the proportion of patients who have HbAlo values at goal. The service was not effective in smoking cessation. This study supports the role of clinical pharmacists in the ambulatory care environment, in collaboration with primary care physicians, in reaching therapeutic goals in diabetic patients. References 1. Rubin RJ, Altman WM, Mendelson ON. Health care expenditures for people with diabetes mellitus, J Clin Endocrinol Metab (4): 809A-809F. 2. O'Brien JA et al. Direct medical costs of complications resulting from type 2 diabetes in the u.s. Diabetes Care Jul; 21(7): American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Clinical Diabetes. 1998; 16: The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med ; 157(21): Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 269(23): Jaber LA et al. Evaluation of a pharmaceutical care model on diabetes management. Ann Pha'rmacother Mar; 30(3): Coast-Senior EA et al. Management of patients with type 2 diabetes by pharmacists in primary care clinics. Ann Pharmacother, 1998 Jun; 32(6): Tiggelaar JM. Protocols for the treatment of essential hypertension and type II diabetes mellitus by pharmacists in ambulatory care clinics. Drug Intell Clin Pharm 1987; 21: Lobas NH, Lepinski pw, Abramowitz PW Effects of pharmaceutical care on medication cost and quality of patient care in an ambulatory-care clinic. Am J Hosp Pharm 1992; 49: Chrischilles EA, Helling OK, Aschoff CR. Effect of clinical pharmacy services on the quality of family practice physicians prescribing and medication costs. mcp Ann Pharmacother 1989; 23: McKenney JM, Witherspoon JM. The impact of outpatient hospital pharmacists on patients receiving antihypertensive and anticoagularit therapy. Hosp Pharm 1985; 20: Gray DR, Garabedian-Ruffalo SM,Chretien SO. Cost-justification of aclinical pharmacist-managed anticoagulation clinic. Drug Intell Clin Pharm 1985;,19: Bond CA, Monson R. Sustained improvement in drug documentation, compliance, and disease control: a four-year analysis of an ambulatory care model. Arch Intern Med 1984; 144: Rodgers PT, James VE. Academic integration into managed care: The why's and how's of partnering. J Managed Care Pharm 1997; 3: diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet (9131): Manson JAE et al. A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch Intern Med 1991; 151: Stamler J et al. Diabetes, other risk factors, and 12 year cardiovascular mortality for men screened in the multiple risk factor intervention trial. Diabetes Care 1993; 16: United Kingdom Prospective Diabetes Study Group. UK Prospective Diabetes Study 23: Risk factors for coronary artery disease in non-insulin dependent diabetes. BMJ 1998; 316: Hypertension in Diabetes Study Group. HDS 2: Increased risk of cardiovascular complications in hypertensive type 2 diabetic patients. J Hypertens 1993; 11: United Kingdom Prospective Diabetes Study Group. UK Prospective Diabetes Study X: Urinary albumin excretion over 3 years in diet-treatedtype 2 (non-insulin-dependent) diabetic patients, and association with hypertension, hyperglycaemia and hypertriglyceridaemia. Diabetologia 1993; 36: Nelson RG et al. Development and progression of renal disease in Pima Indians with non-insulin-dependent diabetes mellitus. N Engl J Med 1996; 335: United Kingdom Prospective Diabetes Study Group. UK Prospective Diabetes Study 30: Diabetic retinopathy at diagnosis of type 2 diabetes and associated risk factors. Arch Ophthalmol1998; 116: Parving HH et al. Effect of antihypertensive treatment on kidney function in diabetic nephropathy. BMJ 1987; 294: Mogensen C et al. Prevention of diabetic renal disease with special reference to microalbuminuria. Lancet 1995; 346: Mogensen CEo Systemic blood pressure and glomerular leakage with particular reference to diabetes and hypertension. J Intern Med 1994; 235: United Kingdom Prospective Diabetes Study Group. Tight control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998; 317: Hansson L, et al. Effects of intensive blood-pressure lowering and lowdose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998; 351(9118): Pyorala K, Pederson TR, Kjekshus J and the Scandinavian SimvaHMG CoA Reductase Inhibitor Survival Study (45) Group. Cholesterol lowering with simvahmg CoA reductase inhibitor improves prognosis of diabetic patients with coronary artery disease. Diabetes Care 1997; 20: Goldberg RB et al. Cardiovascular events and their reduction with pravahmg CoA reductase inhibitor in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. The Care Investigators. Circulation 1998; 98(23): American Diabetes Association: clinical practice recommendations Diabetes Care 1997; 20 Suppl1: American Diabetes Association: clinical practice recommendations Diabetes Care Suppl1: DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulindependent diabetes mellitus. N Englj Med 1993; 329: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 Vol. 6, No.6 NovemberlDecember 2000 jmcp Journal of Managed Care Pharmacy 493