Appendix Evidence Table C119. Overview of glycemic control trials
Study/Region/Funding Source / Inclusion/Exclusion Criteria / Patient Characteristics (expressed in means unless otherwise noted) / Intervention/Duration / Study Quality /
Duckworth, 200985
VADT
Multi-center United States
Funding Source: Government, Foundation, and Industry / Inclusion: Veterans with type 2 diabetes inadequately controlled on maximal doses of an oral agent or insulin therapy.
Exclusion: Glycated hemoglobin <7.5%, cardiovascular event during previous 6 months, advanced congestive heart failure, severe angina, live expectancy <7 years, BMI >40, serum creatinine >1.6 mg/dL, alanine aminotransferase >3 times upper limit of normal / N=491 (subgroup analysis of subjects with baseline microalbuminuria from overall study of N=1,791)
Age (yr): NR
Gender (Male %): NR
Race/Ethnicity (%): NR
Weight (kg): NR
BMI: NR
Systolic BP (mm Hg): NR
Diastolic BP (mm Hg): NR
CKD stage: NR
Serum creatinine (mg/dL): NR
Creatinine clearance (mL/min): NR
Albuminuria (μg/min): NR
Proteinuria (g/day): NR
Albumin/creatinine ratio (mg/g): NR
GFR (ml/min/1.73m2): NR
HbA1c (%): NR
Total cholesterol (mg/dL): NR
LDL cholesterol (mg/dL): NR
Diabetes (%): 100
History of HTN (%): NR
Dyslipidemia (%): NR
History of previous cardiovascular event (%): NR
History of CAD (%): NR
History of CHF (%): NR
Peripheral arterial disease (%): NR
History of MI (%): NR
History of Stroke (%): NR
Current smoker (%): NR
History of AKI (%): NR / Intensive therapy (n=251): Started on maximal doses of oral therapy*; insulin added if patients did not achieve glycated hemoglobin <6%. Subsequent changes per protocol and local assessment, though not specified.
Standard therapy (n=240): Started on ½ of maximal doses of oral therapy*; insulin added if patients did not achieve glycated hemoglobin <9%. Subsequent changes per protocol and local assessment, though not specified.
*Initial oral therapy was metformin plus rosiglitazone if BMI ≥27; initial therapy was glimepiride plus rosiglitazone if BMI <27
Followup period: median 5.6 years
Study withdrawals (%): Reported for overall study, but not for microalbuminuria subgroup / Allocation Concealment: Adequate
Blinding: No
Intention to Treat Analysis (ITT): Yes
Withdrawals/Dropouts adequately described: Yes
Appendix Evidence Table C119. Overview of glycemic control trials (continued)
Study/Region/Funding Source / Inclusion/Exclusion Criteria / Patient Characteristics (expressed in means unless otherwise noted) / Intervention/Duration / Study Quality /
Microalbuminuria Collaborative Study Group, 199586
United Kingdom
Funding Source: Government and Foundation / Inclusion Criteria: Insulin dependent diabetic patients attending 9 hospital-based diabetes centers; ages 16-60; onset of diabetes before age 39; sitting BP <160/95 mm Hg; no antihypertensive treatment; no clinical evidence of cardiovascular, peripheral vascular, or renal disease. Subjects must further have had no albuminuria on urine dipstick, but have had morning urine albumin 15 mg/L or albumin-creatinine ratio 3.5 mg/mmol, followed by overnight urine albumin excretion rate >30μg/min but <200μg/min on at least 1 of 2 samples.
Exclusion Criteria: none stated / N=70
Age (yr): 37.0
Gender (Male %): 72.9
Race/Ethnicity (%): NR
Weight (kg): NR
BMI: 26.0
Systolic BP (mm Hg): 127.5
Diastolic BP (mm Hg): 77.5
CKD stage: NR
Serum creatinine (mg/dL): 0.97
Creatinine clearance (mL/min): NR
Albuminuria (μg/min): 47.9
Proteinuria (g/day): NR
Albumin/creatinine ratio (mg/g): NR
GFR (ml/min/1.73m2): 116.7
HbA1c (%): 10.1
Total cholesterol (mg/dL): NR
LDL cholesterol (mg/dL): NR
Diabetes (%): 100
History of HTN (%): NR
Dyslipidemia (%): NR
History of CAD (%): NR
History of CHF (%): NR
Peripheral arterial disease (%): NR
History of MI (%): NR
History of Stroke (%): NR
Current smoker (%): 47.1
History of AKI (%): NR / Intensive therapy (n=36): Insulin by continuous infusion or multiple daily injections; goals were glycated hemoglobin concentration ≤7.5%, fasting blood glucose 4-6 mmol/l, and 2 hr postprandial blood glucose ≤10 mmol/l. Frequent visits and medication adjustment were made as needed to achieve targets. 24 hr/day consultation available if needed.
Conventional therapy (n=34): 2 daily injections of insulin (except for 9 patients who were receiving >2 doses insulin per day at baseline); Conventional education given about diet, exercise and blood glucose monitoring, but no targets set. Insulin dose and regimen was adjusted only if patients became symptomatic.
No changes were made to the usual diabetic diet of any patient. BP was assessed every 3 months, and all patients were treated to keep BP <160/95.
Followup period: median 5 years
Study withdrawals (%): 11.4 / Allocation Concealment: Adequate (central location)
Blinding: Unclear
Intention to Treat Analysis (ITT): Yes
Withdrawals/Dropouts adequately described: Yes
ACEI = angiotensin converting enzyme inhibitor; ACR = albumin/creatinine ratio; AER = albumin excretion rate; AKI = acute kidney injury; ARB = angiotensin II receptor blocker; BB = bete blocker; BMI = body mass index; BP = blood pressure; CAD = coronary artery disease; CCB = calcium channel blocker; CHD = coronary heart disease; CHF = congestive heart failure; CKD = chronic kidney disease; CV = cardiovascular; CVA = cerebrovascular accident; DBP = diastolic blood pressure; DM = diabetes mellitus; GFR = glomerular filtration rate; HbA1c = hemoglobin A1c; HTN = hypertension; LDL = low density lipoprotein; LVEF = left ventricular ejection fraction; MI = myocardial infarction; NR = not reported; NSAIDS = non-steroidal anti-inflammatory drug; PVD = peripheral vascular disease; RCT = randomized controlled trial; SBP = systolic blood pressure; UACR = urinary albumin/creatinine ratio; UAE = urinary albumin excretion