Evidence Table 19

Adverse events in observational studies, ROSI

Author
Year
Quality score
Study design
Country
Population
Inclusion criteria
Exclusion criteriaAge (y)
Gender (% male)
Race/ethnicity
InterventionAuthor Year Quality scoreOther medications permittedMethod and timing of AE assessmentAdverse events
Freed MI
2002
RCTDM2
Patients with DM2, aged 35 to 80y, FPG <=160 mg/dl if previously treated with diet and exercise only, or <=220 mg/dl if treated with a SU; TG<=500 mg/dl; LDL <=160 mg/dl; acceptable glycemic control
LDL <100 mg/dl in the absence of a lipid-lowering agent at screening; renal or hepatic disease; jaundice; severe hypertriglyceridemia; New York Heart Association class III/IV congestive heart failure; angina or coronary insufficiency; anemia; SBP>180 mm Hg; DBP>110 mm Hg; history of drug or alcohol abuse; taking anorectic agents; taking any medication affecting cytochrome P450 3A enzyme system60(10)
NR
NR
Addition of atorvastatin or placebo to rosiglitazoneFreed MI 2002SUMethod NR
AEs assessed during 8-w open-label run-in period and at 24w
During 8-w run-in period (on ROSI), 56% experienced AE:
- hypoglycemia: 11% (most on SU)
- URTI: 7%
- edema: 5%
- hematocrit: change -5.3%
- weight: change 1.4–1.7kg

Double-blind 16-w treatment phase (on
ROSI and atorvastatin):
- similar AEs to 8-w phase
- weight: change 2.0–2.5kg
- no hepatic AES, no change LFT
- no apparent musculoskeletal toxicity
Kiayias
2002
Cohort with comparison
Greece
DM2NRMean Age: 58.6
Male (52.6%)
Ethnicity: 100% Greek
Rosiglitazone 4 or 8mg daily, added to metformin and SUKiayias
2002
NRMethod NR
AE's, A1c, FPG, liver function assessed at 20 weeks
Cohort with comparison, at 20 weeks of treatment with ROSI with SU and metformin:
- Hypoglycemia (18.6% at 4 mg/day,
4.6% at 8 mg/day)
- Mean body weight increase (4.2 kg at
4mg/day and 4.6 kg at 8mg/day)
- No signs found of liver disease/dysfunction
Marceille, J
2004
Retrospective cohort
USA
DM2
prescribed ROSI before 10/01, prescribed insulin, over 18 years of age, followed at Hines Veterans Affairs Hospital or outpatient clinic
Patients not receiving insulin before start of ROSI, or received ROSI after care at Hines, refill records/chart documentation showing non- compliance wth ROSI or insulinAge Range: 18-up
Male: (98.5%)
Caucasian: 69.7%
African-American:
21.5%
Asian: 1.4%
Other: 7.1%
ROSI (doses varied/NR) with insulinMarceille, J
2004
NRMethod NR, assessments taken at baseline and 12 monthsRetrospective cohort study of ROSI and insulin, at 12 months (p-value from baseline):
- shortness of breath: 14%; p=0.07
- dyspnea on exertion: 9.4%; p=0.75
- paroxysmal nocturnal dyspnea: 3.6%;
p=0.16
- lower extremity edema: 36%;
p<0.0001
- cough: 1.4%; p=0.16
- pulmonary edema: 0; p=0.32
- jugular venous distention: 2.9%;
p=0.53
- hepatomegaly: 2.2%; p=0.08
rales: 4.3%; p=0.68
Miyazaki, Y
2005
Before-After Study
USA
DM2, aged 30–70 years, BMI < 37kg/m, stable body weight for 3 months before entry, FPG between 140–260 mg/dLPatients with previous use of insulin, metformin or another TZD, cardiac, hepatic, renal or other chronic diseases as determined by history or current tests, participation in heavy exercise, use of medications known to effect glucose metabolism, other than SUsMean Age: 54
Male: (48.6%)
White: 29.7%
Mexican-American:
70.2%
ROSI 8mg/day, 13 subjects also receiving SU, 24 subjects treated with diet/no SUMiyazaki, Y
2005
NR75g oral glucose test and determination of body fat, before and after 12 weeks FPG (glucose oxidase method) and body weight assessed every 2 weeks, A1c (affinity chromatography) and fasting plasma lipids (enzymatically) assessed twice between baseline and 12 weeks, At 10 weeks, blood drawn following at 10–12 hour fastBefore-after study of ROSI with and diet or SU, at 12 weeks: -
increase noted in body weight, BMI, fat percentage, plasma total cholestrol, LDL-cholestrol, dn HDL-cholestrol
Orbay, E
2004
Cohort Study
Turkey
Insufficiently controlled DM2 receiving glimepiride and metformin therapy for at least 12 months, constant doses for at least 2 months before entry, aged 40–70 years, FPG between 126– 270 mg/dl, A1c levels between 7.0–8.0% at screeningPatients with significant renal or hepatic impairment, hypertension, anemia, cardiac insufficiency, symptomatic diabetic neuropathy, pregnancy, significant abnormalities in exam at screening, previous participation in any ROSI study or investigational drug within 30 days of screeningMean Age: 56.83
Male: (56.6%)
Ethnicity NR
ROSI 4mg daily with 3 mg glimepiride twice daily and 850 mg metformin twice dailyOrbay, E
2004
NRPhysical exams, vital signs measurement, weight measurement, electocardiogram, adverse event query, lab testsOpen-label study of ROSI added to SU and metformin, at 26 weeks:
- elevations in aminotransferase and aspartate aminotransferase not found
- Patients reported of hypoglycemia, not considered serious
Osei, K
2004
Cohort with comparison
USA
DM2 or IGT
First-degree relatives of African-Americans with DM2 (n=12), compared with relatives with normal glucose tolerance (n=19)
Patients with symptoms of hyperglycemia, taking medications known to influence glucose and insulin metabolism, with liver, heart, lung and kidney diseases, established diabetes on antidiabetic medications, participation in endurance exercise or regular competitive sportsMean Age:49.7
Gender: NR
Ethnicity: 100%
African-American
Patients with DM2/IGT received ROSI at 4mg/day for first 4 weeks, then increased to 8 mg/day (single dose) from 4–12 weeksOsei, K
2004
NRBlood tests, liver and renal tests, A1c levels assessed at baseline and 12 weeksCohort with comparison, at 12 weeks of treatment with ROSI 8mg/day:
- No significant weight gain found
- No discernable clinical pitting edema found
Pietruck, F
2005
Before-After Study
Germany
NODM after renal transplantationNRMean Age: 55
Male: (50%)
Ethnicity NR
ROSI 4mg/day starting, 8mg/day maximumPietruck, F
2005
Predisone, tacrolimus, cyclosporine,Method/timing of assessments
NR
Before-after study of ROSI, - one patient discontinued/excluded after 5 days due to edema and weight gain of 4 kg
- one patient received additional antidiabetic after 14 months
Roy, R
2004
Cohort Study
USA
DM2NRMean Age: 51.0
Male (35.4%)
Latino: 83.3%
African-American: 14.5%
East Indian: 2%
Rosiglitazone 8mg daily, added to metformin and SURoy, R
2004
NRMethod NR
AE's, A1c assessed at 12 months
Observational, at 12 months of treatment of ROSI, with metformin and SU:
- edema in 2 patients (4.1%)
Sarafidis, P
2004
Cohort Study
Greece
DM2
poorly glycemic control, poorly controlled/newly diagnosed hypertension
NRMean Age: 63.8
Male (45%)
Ethnicity NR
Rosiglitazone 4mg daily, added to SUSarafidis, P
2004
Anti-hypertensive medicationsClinic visits ever 2 months for 26 weeks: physical exams, rountine lab tests, insulin sensitivity assessed with clampObservational, at 26-weeks of treatment of ROSI added to SU:
- No elevation of liver function tests above normal
- No complaints of leg edema or heart failure symptoms
- No laboratory/clinical finding of anemia or renal function deterioration

From: Evidence Tables

Cover of Drug Class Review: Thiazolidinediones
Drug Class Review: Thiazolidinediones: Final Report Update 1 [Internet].
Norris SL, Carson S, Thakurta S, et al.
Portland (OR): Oregon Health & Science University; 2008 Aug.
Copyright © 2008, Oregon Health & Science University, Portland, Oregon.

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