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Long-term effects of weight-reducing drugs in hypertensive patients

  1. Andrea Siebenhofer1,*,
  2. Klaus Jeitler2,
  3. Karl Horvath3,
  4. Andrea Berghold4,
  5. Ulrich Siering5,
  6. Thomas Semlitsch6

Editorial Group: Cochrane Hypertension Group

Published Online: 28 MAR 2013

Assessed as up-to-date: 15 JAN 2013

DOI: 10.1002/14651858.CD007654.pub3


How to Cite

Siebenhofer A, Jeitler K, Horvath K, Berghold A, Siering U, Semlitsch T. Long-term effects of weight-reducing drugs in hypertensive patients. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD007654. DOI: 10.1002/14651858.CD007654.pub3.

Author Information

  1. 1

    Goethe University, Institute for General Practice, Frankfurt am Main, Germany

  2. 2

    Medical University of Graz, EBM Review Center, Department of Internal Medicine and Institute for Medical Informatics, Statistics and Documentation, Graz, Austria

  3. 3

    Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Metabolism, Graz, Austria

  4. 4

    Medical University of Graz, Institute for Medical Informatics, Statistics and Documentation, Graz, Austria

  5. 5

    Institute for Quality and Efficiency in Health Care, Quality of Health Care, Köln, Germany

  6. 6

    and HEALTH - Institute of Medical Technologies and Health Management, Joanneum Research, EBM Review Center, Department of Internal Medicine, Medical University of Graz, Graz, Austria

*Andrea Siebenhofer, Institute for General Practice, Goethe University, Theodor-Stern-Kai 7, Frankfurt am Main, 60590, Germany. andrea.siebenhofer@medunigraz.at.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 28 MAR 2013

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This is not the most recent version of the article. View current version (02 MAR 2016)

 
Characteristics of included studies [author-defined order]
Bakris 2002

MethodsDESIGN: parallel, randomized, double-blind

DURATION: 12 months

NUMBER OF STUDY CENTRES: 41

COUNTRY OF PUBLICATION: USA


ParticipantsWHO PARTICIPATED: obese patients with insufficiently controlled hypertension

SETTING: outpatient clinic

MAIN INCLUSION CRITERIA: age ≥ 40 years, BMI 28-43 kg/m2, at least one antihypertensive medication, sitting diastolic blood pressure 96-109 mm Hg

MAIN EXCLUSION CRITERIA: recent initiation or change in diuretic therapy, previous gastrointestinal surgery for weight reduction, active gastrointestinal disorders, use of nicotine replacement therapy, appetite suppressants, fish-oil supplements, chronic systemic steroids, acute antidepressant or anxiolytic therapy

GENERAL BASELINE CHARACTERISTICS (Orlistat vs. Placebo)

NUMBER: 278 vs. 276 were randomized, 267 vs. 265 were analysed

MEAN AGE [YEARS]: 53 vs. 53

GENDER [% MALE]: 37% vs. 41%

NATIONALITY: USA

ETHNICITY: 85-86% white; 11-12% blacks, 1-4% hispanics, 0-1% other

WEIGHT [kg]: 101 vs. 102 

BODY MASS INDEX [kg/m2]: 36 vs. 35 

SITTING SYSTOLIC BLOOD PRESSURE [mm Hg]: 154 vs. 151 

SITTING DIASTOLIC BLOOD PRESSURE [mm Hg]: 98 vs. 98 

CO-MORBID CONDITIONS: 8% diabetes in both groups

ANTIHYPERTENSIVE TREATMENT. 95% vs. 94%

DURATION OF HYPERTENSION: -

 

SUBGROUP: diabetic patients (no information on reasons and method are noted)


InterventionsINTERVENTION (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Orlistat 120 mg three times a day with meals

CONTROL (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Placebo three times a day with meals

ADDITIONAL TREATMENT:

hypocaloric diet, lifestyle intervention, moderate physical activity


OutcomesLENGTH OF FOLLOW-UP: 12 months

PRIMARY OUTCOMES:

1. MORTALITY: -

2. CARDIOVASCULAR MORBIDITY: -

3. ADVERSE EVENTS:

Definition: reported were serious adverse events as necessitating or prolonging hospitalization; withdrawals due to adverse events; gastrointestinal and musculoskeletal symptoms

SECONDARY OUTCOMES:

1. CHANGES IN SYSTOLIC BLOOD PRESSURE [mm Hg]

Definition: sitting systolic blood pressure change from baseline to endpoint visit

2. CHANGES IN DIASTOLIC BLOOD PRESSURE [mm Hg]

Definition: sitting diastolic blood pressure change from baseline to endpoint visit

3. BODY WEIGHT [kg]

Definition: body weight change from baseline to endpoint visit

ADDITIONAL OUTCOMES MEASURED IN THE STUDY:

  1. BMI [kg/m2]
  2. Antihypertensive medication
  3. Number of patients who reach goal blood pressure
  4. Change in waist circumference
  5. Change in insulin concentration
  6. Changes in lipid parameters
  7. >30% reduction in cardiovascular composite risk


NotesSPONSOR: Roche Laboratories, New Jersey; USA


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo details on generation sequence are provided.

Allocation concealment (selection bias)Unclear riskMethod of concealment is not described.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote: "... randomized, double-blind, placebo-controlled study..."

No details provided to assure that blinding of participants and key study personnel has not been broken.

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "... statistical analyses were performed on an ITT basis ..."

Last observation was carried forward and reasons and description for withdrawals are provided.

 ----------------------------------------------------------------------

WITHDRAWALS: 116 vs. 168 (Orlistat vs. Placebo)

REASONS / DESCRIPTIONS (Orlistat vs. Placebo):

   - adverse events: 18 vs. 20 

   - refused treatment: 40 vs. 91 

   - lost to follow-up: 48 vs. 47 

   - other: 8 vs. 9 

   - excluded: 2 vs. 1

Selective reporting (reporting bias)High riskNo study protocol, outcomes are reported that were not pre-specified (e.g. systolic blood pressure).

Other biasHigh risk1. The combination of a high withdrawal rate and the unknown duration of participation in the trial increases risk of bias even using the LOCF analysis.

2. There are inconsistencies in reporting between text and flowchart on the numbers of patients who finished the study.

Cocco 2005

MethodsDESIGN: parallel, randomized, double-blind

DURATION OF INTERVENTION: 6 months

NUMBER OF STUDY CENTRES: 1

COUNTRY OF PUBLICATION: Switzerland


ParticipantsWHO PARTICIPATED: obese patients with metabolic syndrome, diabetes type 2, hypertension, mostly with coronary heart disease and concomitant cardiac dysfunction

SETTING: outpatient clinic

MAIN INCLUSION CRITERIA: age ≥ 35 years, BMI 31-40 kg/m2, left ventricular function 42-50%

MAIN EXCLUSION CRITERIA: inability of subjects to monitor their own glucose and blood pressure, active participation in a dietary program, use of weight-losing medication

GENERAL BASELINE CHARACTERISTICS (Orlistat vs. Placebo)

NUMBER: 45 vs. 45

MEAN AGE [YEARS]: 55 vs. 55

GENDER [% MALE]: 49% vs. 49%

NATIONALITY: probably Swiss

ETHNICITY: 100% white

WEIGHT [kg]: 107 vs. 106

HbA1c: 7.3% vs. 6.9%

BODY MASS INDEX [kg/m2]: 37 vs. 36

SYSTOLIC BLOOD PRESSURE [mm Hg]: 146 vs. 142

DIASTOLIC BLOOD PRESSURE [mm Hg]: 88 vs. 85

CO-MORBID CONDITIONS: 100% metabolic syndrome and diabetes, 77% coronary heart disease, 47% myocardial infarction

ANTIHYPERTENSIVE TREATMENT: 100%

DURATION OF HYPERTENSION: -

SUBGROUP: -


InterventionsINTERVENTION (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Orlistat 120 mg three times a day

CONTROL (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Placebo three times a day

ADDITIONAL TREATMENT:

hypocaloric diet, teaching sessions for lifestyle intervention, moderate physical activity


OutcomesLENGTH OF FOLLOW-UP: 6 months

PRIMARY OUTCOMES:

1. MORTALITY: -

2. CARDIOVASCULAR MORBIDITY: -

3. ADVERSE EVENTS:

Definition: gastrointestinal side effects were reported (no severe effects)

SECONDARY OUTCOMES:

1. CHANGES IN SYSTOLIC BLOOD PRESSURE [mm Hg]

Definition: systolic blood pressure change from baseline to endpoint visit

2. CHANGES IN DIASTOLIC BLOOD PRESSURE [mm Hg]

Definition: diastolic blood pressure change from baseline to endpoint visit

3. BODY WEIGHT [kg]

Definition: body weight change from baseline to endpoint visit

ADDITIONAL OUTCOMES MEASURED IN THE STUDY:

  1. BMI [kg/m2]
  2. Caloric consumption
  3. Changes in lipid- and glucose parameters
  4. Change in insulin concentration
  5. Change in heart rate and left ventricular ejection fraction
  6. Changes in uric acid concentrations


NotesSPONSOR: -


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "To ensure that each group would contain approximately equal numbers of risk factors, stratified randomization was used with an algorithm generated from a random set of numbers."

Allocation concealment (selection bias)Unclear riskMethod of concealment is not described.

Blinding (performance bias and detection bias)
All outcomes
Low riskAuthors' reply gave further detailed information that patients, study personnel and outcome assessment were blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data.

Selective reporting (reporting bias)High riskNo study protocol or reporting on pre-specified endpoint, no primary endpoint reported.

Other biasLow risk-similar baselines

- only small inconsistencies between changes in body weight in the table and text in comparison with calculated numbers in the table

Guy-Grand 2004

MethodsDESIGN: parallel, randomized, double-blind

DURATION OF INTERVENTION: 6 months

NUMBER OF STUDY CENTRES: 253

COUNTRY OF PUBLICATION: France


ParticipantsWHO PARTICIPATED: obese patients with diabetes type 2, hypertension, or hypercholesterolaemia; only the predefined subgroup of hypertensive patients is reported here

SETTING: private endocrinologists

MAIN INCLUSION CRITERIA: age 18-65 years, BMI 28-40 kg/m2, diastolic blood pressure 90-110 mm Hg or untreated hypertensives or treatment stopped for more than 3 months or insufficiently controlled by the last 6 months of treatment

MAIN EXCLUSION CRITERIA: secondary hypertension, history or presence of drug and alcohol abuse, significant cardiac, renal, hepatic gastrointestinal, endocrine and psychiatric disorders

GENERAL BASELINE CHARACTERISTICS (Orlistat vs. Placebo)

NUMBER: 304 vs. 310

MEAN AGE [YEARS]: 49 vs. 50

GENDER [% MALE]: 31% vs. 35%

NATIONALITY: probably French

ETHNICITY: -

WEIGHT [kg]: 94 vs. 94

BODY MASS INDEX [kg/m2]: 34 vs. 34

SITTING SYSTOLIC BLOOD PRESSURE [mm Hg]: 150 vs. 152

DIASTOLIC BLOOD PRESSURE [mm Hg]: 97 vs. 97

CO-MORBID CONDITIONS: -

ANTIHYPERTENSIVE TREATMENT: 70%

DURATION OF HYPERTENSION: -

SUBGROUP: -


InterventionsINTERVENTION (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Orlistat 120 mg three times a day with meals

CONTROL (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Placebo three times a day with meals

ADDITIONAL TREATMENT:

hypocaloric diet


OutcomesLENGTH OF FOLLOW-UP: 6 months

PRIMARY OUTCOMES:

1. MORTALITY: -

2. CARDIOVASCULAR MORBIDITY: -

3. ADVERSE EVENTS:

Definition: Gastrointestinal events are only reported for the whole study population having diabetes type 2, hypertension, or hypercholesterolaemia.

SECONDARY OUTCOMES:

1. CHANGES IN SYSTOLIC BLOOD PRESSURE [mm Hg]

Definition: systolic blood pressure change from baseline to endpoint visit

2. CHANGES IN DIASTOLIC BLOOD PRESSURE [mm Hg]

Definition: diastolic blood pressure change from baseline to endpoint visit

3. BODY WEIGHT [kg]

Definition: body weight change from baseline to endpoint visit

ADDITIONAL OUTCOMES MEASURED IN THE STUDY:

  1. BMI [kg/m2]
  2. Changes in lipid- and glucose parameters
  3. Dosage of concomitant treatment
  4. Change in waist circumference
  5. Change in insulin concentration
  6. Change in pulse pressure


NotesSPONSOR: Roche Pharma, Paris, France


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomization was performed by a centralized procedure in which patients were stratified by both centre and comorbidity. According to minimization procedure, patients were randomized to ensure that treatment groups were well balanced by both centre and by concomitant disease."

Allocation concealment (selection bias)Low riskCentral allocation

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote: "... randomized, double-blind, placebo controlled, parallel-group study ..."

No details provided to ensure that blinding of participants and key study personnel was not broken.

Incomplete outcome data (attrition bias)
All outcomes
High riskQuote: "Efficacy was assessed on an intent-to-treat (ITT) basis. The ITT population included all randomized patients and the safety population consisted of all randomized patients who had received at least one dose of study treatment. Principal criteria missing at six months were replaced by the last-measured value (last observation carried forward, LOCF)."

 ----------------------------------------------------------------------

WITHDRAWALS and LOST TO FOLLOW UP:

REASONS / DESCRIPTIONS: only reported for the whole study population having diabetes type 2, hypertension, or hypercholesterolaemia.

Selective reporting (reporting bias)High riskNo study protocol

Other biasLow risk- Similar baselines

- Power calculation is provided

XENDOS 2001-2006

MethodsDESIGN: parallel, randomized, double-blind

DURATION OF INTERVENTION: 48 months

NUMBER OF STUDY CENTRES: 22

COUNTRY OF PUBLICATION: Sweden


ParticipantsWHO PARTICIPATED: obese patients with normal or impaired glucose tolerance. Only the predefined subgroup of hypertensive patients is reported here. Data were obtained from the publicly available scientific report of the Institute for Quality and Efficiency in Health Care (IQWiG 2006)

SETTING: medical centres

MAIN INCLUSION CRITERIA: age 30-60 years, BMI ≥ 30 kg/m2, normal or impaired glucose tolerance, either diastolic blood pressure ≥90 mm Hg (first pre-defined subgroup) or systolic blood pressure ≥140 mm Hg (second pre-defined subgroup)

MAIN EXCLUSION CRITERIA: systolic blood pressure >165 mm Hg or diastolic blood pressure > 105 mm Hg, diabetes mellitus, ongoing and active cardiovascular and gastrointestinal disease

BASELINE CHARACTERISTICS OF THE FIRST SUBGROUP: (Orlistat vs. Placebo)

NUMBER: 408 vs. 441 were randomized and 407 vs. 437 were analysed

MEAN AGE [YEARS]: 46 vs. 46

GENDER [% MALE]: 62% vs. 56%

NATIONALITY: Swedish

ETHNICITY: -

WEIGHT [kg]: 116 vs. 114

BODY MASS INDEX [kg/m2]: -

SYSTOLIC BLOOD PRESSURE [mm Hg]: 146 vs. 146

DIASTOLIC BLOOD PRESSURE [mm Hg]: 95 vs. 95

CO-MORBID CONDITIONS: -

ANTIHYPERTENSIVE TREATMENT: -

DURATION OF HYPERTENSION: -

BASELINE CHARACTERISTICS OF THE SECOND SUBGROUP: (Orlistat vs. Placebo)

NUMBER: 516 vs. 509 were randomized and 513 vs. 508 were analysed

MEAN AGE [YEARS]: 47 vs. 47

GENDER [% MALE]: 58% vs. 58%

NATIONALITY: Swedish

ETHNICITY: -

WEIGHT [kg]: 116 vs.115

BODY MASS INDEX [kg/m2]: -

SYSTOLIC BLOOD PRESSURE [mm Hg]: 149 vs.149

DIASTOLIC BLOOD PRESSURE [mm Hg]: 91 vs.91

CO-MORBIDID CONDITIONS: -

ANTIHYPERTENSIVE TREATMENT: -

DURATION OF HYPERTENSION: -


InterventionsINTERVENTION (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Orlistat 120 mg three times a day with meals

CONTROL (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Placebo three times a day with meals

ADDITIONAL TREATMENT:

hypocaloric diet, teaching sessions for lifestyle intervention, moderate physical activity


OutcomesLENGTH OF FOLLOW-UP: 48 months

PRIMARY OUTCOMES:

1. MORTALITY: -

2. CARDIOVASCULAR MORBIDITY: -

3. ADVERSE EVENTS:

Definition: severe, overall and withdrawals were reported, further reported were gastrointestinal, musculoskeletal, dermatological, vascular and nervous side effects.

SECONDARY OUTCOMES:

1. CHANGES IN SYSTOLIC BLOOD PRESSURE [mm Hg]

Definition: systolic blood pressure change from baseline to endpoint visit

2. CHANGES IN DIASTOLIC BLOOD PRESSURE [mm Hg]

Definition: diastolic blood pressure change from baseline to endpoint visit

3. BODY WEIGHT [kg]

Definition: body weight change from baseline to endpoint visit

ADDITIONAL OUTCOMES MEASURED IN THE STUDY:

  1. Time to onset of type 2 diabetes
  2. Time to onset of hypertension
  3. Changes in anthropometric measurements, metabolic profile and glucose parameters
  4. Time to onset of IGT


NotesSPONSOR: Hoffmann-La Roche, Nutley, (NJ) USA


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskInformation obtained from the scientific report (IQWiG 2006)

Allocation concealment (selection bias)Low riskInformation obtained from the scientific report (IQWiG 2006)

Blinding (performance bias and detection bias)
All outcomes
Unclear riskInformation obtained from the scientific report (IQWiG 2006)

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskInformation obtained from the scientific report (IQWiG 2006)

Quote: "Efficacy was assessed on an intention-to treat (ITT) basis with a last observation carried forward principle (LOCF). The ITT population included all randomized patients who had received at least one dose of study treatment and one follow up examination." 

 ---------------------------------------------------------------------- 

First subgroup

WITHDRAWALS: 183 (45%) vs. 268 (61%) (Orlistat vs. Placebo)

 REASONS / DESCRIPTIONS (Orlistat vs. Placebo)

   - study withdrawals 22 (5%) vs. 20 (5%)

   - adverse events: 9% vs. 4% 

   - no further reasons mentioned

 

Second subgroup

WITHDRAWALS: 215 (42%) vs. 307 (60%) (Orlistat vs. Placebo)

 REASONS/DESCRIPTIONS (Orlistat vs. Placebo)

   - study withdrawals 25 (4%) vs. 22 (5%)

   - adverse events: 9% vs. 4% 

   - no further reasons mentioned

Selective reporting (reporting bias)Unclear riskInformation was only obtained from the scientific report (IQWiG 2006) and no publication in full was available to allow judgement of either yes or no.

Other biasHigh risk- combination of a high withdrawal rate and the unknown length of stay of participants in the trial increases risk of bias even using the LOCF analysis

-similar baselines

- power calculation is only provided for the whole group

Fanghaenel 2003

MethodsDESIGN: parallel, randomized, double-blind

DURATION OF INTERVENTION: 6 months

NUMBER OF STUDY CENTRES: 1

COUNTRY OF PUBLICATION: Mexico


ParticipantsWHO PARTICIPATED: obese patients with hypertension

SETTING: Endocrinology Service of the General Hospital of Mexico

MAIN INCLUSION CRITERIA: BMI > 27 kg/m2, after 2 weeks of antihypertensive washout diastolic blood pressure  90 - 109 mm Hg or systolic blood pressure ≥140 mm Hg, then start with antihypertensive treatment unless blood pressure was <140/90 mm Hg.

MAIN EXCLUSION CRITERIA: uncontrolled hypertension, thyroid-replacement drugs, endocrine (other than type 2 diabetes mellitus) disease,  autoimmune or ischemic heart diseases, arrhythmia, or diuretic treatment

GENERAL BASELINE CHARACTERISTICS (Sibutramine vs. Placebo)

NUMBER: 66 were randomized (no details to which treatment group), 29 vs. 28 were analysed

MEAN AGE [YEARS]: 49 vs. 46

GENDER [% MALE]: 17% vs. 25%

NATIONALITY: Mexican

ETHNICITY: Hispanic (Latin-Americans)

WEIGHT [kg]: 75 vs. 78

BODY MASS INDEX [kg/m2]: 31 vs. 31

SYSTOLIC BLOOD PRESSURE [mm Hg]: 139 vs. 139

DIASTOLIC BLOOD PRESSURE [mm Hg]: 93 vs. 92

CO-MORBID CONDITIONS: hypertension

ANTIHYPERTENSIVE TREATMENT: 100%

DURATION OF HYPERTENSION: -

 

SUBGROUP: -


InterventionsINTERVENTION (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Sibutramine 10 mg once a day

CONTROL (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Placebo once a day

ADDITIONAL TREATMENT:

hypocaloric diet


OutcomesLENGTH OF FOLLOW-UP: 6 months

PRIMARY OUTCOMES:

1. MORTALITY: -

2. CARDIOVASCULAR MORBIDITY: -

3. ADVERSE EVENTS:

Definition: reported adverse events such as headache, gastrointestinal events, insomnia

SECONDARY OUTCOMES:

1. CHANGES IN SYSTOLIC BLOOD PRESSURE [mm Hg]:

Definition: baseline and follow up measurements are provided and change can be calculated.

2. CHANGES IN DIASTOLIC BLOOD PRESSURE [mm Hg]:

Definition: baseline and follow up measurements are provided and change can be calculated.

3. BODY WEIGHT [kg]

Definition: body weight change from baseline to endpoint visit

ADDITIONAL OUTCOMES MEASURED IN THE STUDY:

  1. Change in antihypertensive treatment
  2. BMI [kg/m2]
  3. Change in waist circumference
  4. Change in waist-to-hip ratio (WHR)
  5. Changes in heart rate and electrocardiograms
  6. Changes in laboratory parameters


NotesSPONSOR: Química Knoll de México, Mexico


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "... prepared a computer list of 70 random numbers in seven blocks of 10 ..."

Allocation concealment (selection bias)Low riskQuote: "... opaque sealed envelope with drug  code ..."

Blinding (performance bias and detection bias)
All outcomes
Low riskAccording to text in the publication blinding of participants and key study personnel can be ensured. It was unclear if outcome assessment was blinded. 

Incomplete outcome data (attrition bias)
All outcomes
High risk66 patients were randomized and 9 patients withdrew during run-in period without knowing to which group the patients had been randomized.

 ----------------------------------------------------------------------  

WITHDRAWALS and LOST TO FOLLOW UP (Sibutramine vs. Placebo): only reported for the patients who were included in the completers analysis

REASONS / DESCRIPTIONS (Sibutramine vs. Placebo):

- lost to follow up: 1 vs. 2

- protocol violation: 2 vs. 1

- withdrew consent: 3 vs. 1

Selective reporting (reporting bias)High riskNo study protocol and

patient flow is inconsistent.

Other biasHigh riskAs 14% of randomized patients (unclear of which treatment group) were not included in the analysis it can be judged that the handling with dropouts is inadequate.

Faria 2002

MethodsDESIGN: parallel, randomized, double-blind

DURATION OF INTERVENTION: 6 months

NUMBER OF STUDY CENTRES: 1

COUNTRY OF PUBLICATION: Brazil


ParticipantsWHO PARTICIPATED: obese hypertensive patients

SETTING: hypertension outpatient clinic of Hospital do Rim e da Hipertensão

MAIN INCLUSION CRITERIA: BMI ≥ 30 to < 50kg/m2, office systolic blood pressure ≥ 140 mm Hg and diastolic blood pressure >90 and < 110 mm Hg or < 95 mm Hg if on antihypertensive therapy, waist/hip ratio (WHR) ≥ 0.85 for women and ≥ 0.95 for men

MAIN EXCLUSION CRITERIA: diabetes (fasting glucose of over 7.05 mmol/l), severe dyslipidaemia (cholesterol levels of ≥ 7.74 mmol/l and triglyceride levels of ≥ 4.51 mmol/l), congestive heart failure, coronary heart disease, renal or hepatic insufficiency

GENERAL BASELINE CHARACTERISTICS for the analysed patients (Sibutramine vs. Placebo)

NUMBER: 56 vs. 53 were randomized, 43 vs. 43 were analysed

MEAN AGE [YEARS]: 46 vs. 51

GENDER [% MALE]: 17% vs. 12%

NATIONALITY: Brazil

ETHNICITY: -

WEIGHT [kg]: 100 vs. 97 

BODY MASS INDEX [kg/m2]: 40 vs. 39

24-h SYSTOLIC BLOOD PRESSURE [mm Hg]: 150 vs. 150 

24-h DIASTOLIC BLOOD PRESSURE [mm Hg]: 91 vs. 94

CO-MORBID CONDITIONS: -

ANTIHYPERTENSIVE TREATMENT. 81% vs. 81%

DURATION OF HYPERTENSION: -

 

SUBGROUP: -


InterventionsINTERVENTION (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Sibutramine 10 mg once a day in the morning

CONTROL (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Placebo once a day in the morning

ADDITIONAL TREATMENT:

hypocaloric diet, increased physical activity


OutcomesLENGTH OF FOLLOW-UP: 6 months

PRIMARY OUTCOMES:

1. MORTALITY: -

2. CARDIOVASCULAR MORBIDITY: -

3. ADVERSE EVENTS: -

Definition: reported as symptoms such as dry mouth, and joint pain

SECONDARY OUTCOMES:

1. CHANGES IN SYSTOLIC BLOOD PRESSURE [mm Hg]

Definition: systolic blood pressure at baseline and at endpoint visit

2. CHANGES IN DIASTOLIC BLOOD PRESSURE [mm Hg]

Definition: diastolic blood pressure at baseline and at endpoint visit

3. BODY WEIGHT [kg]

Definition: body weight at baseline and at endpoint visit

ADDITIONAL OUTCOMES MEASURED IN THE STUDY:

  1. Body fat mass
  2. Change in heart rate
  3. Change in antihypertensive medication
  4. Change in ventricular hypertrophy
  5. Change in waist circumference
  6. Change in insulin concentration
  7. Changes in laboratory parameters
  8. Change in waist/hip ratio
  9. Change in BMI


NotesSPONSOR: Abbott Laboratories of Brazil


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo details on generation sequence are provided.

Allocation concealment (selection bias)Low riskQuote: "... administration of sequential numbers ..."

Blinding (performance bias and detection bias)
All outcomes
Low riskAccording to personal communication with one of the authors of this Cochrane review (U.S.) it can be assured that blinding of patients, study personal and outcome assessors can be guaranteed. 

Incomplete outcome data (attrition bias)
All outcomes
High riskNo missing data but no ITT analysis, only a completers analysis was performed.

 ----------------------------------------------------------------------   

WITHDRAWALS: 13 vs. 10 (Sibutramine vs. Placebo)

REASONS / DESCRIPTIONS (Sibutramine vs. Placebo)

-  loss of compliance: 7 vs. 8

- biochemical abnormalities: 1 vs. 1

- increases of BP: 1 vs. 1

- introduction of corticoid therapy: 1 vs. 2

- urinary infection: 0 vs. 1

Selective reporting (reporting bias)High riskNo study protocol, small differences in reporting between the two publications in 2002 and 2005.

Other biasHigh riskThere was inadequate handling of dropouts in the analyses, it is unclear whether patients were comparable for prognosis-relevant factors at baseline.

McMahon 2000

MethodsDESIGN: parallel, randomized, double-blind

DURATION OF INTERVENTION: 12 months

NUMBER OF STUDY CENTRES: multicenter (numbers unclear)

COUNTRY OF PUBLICATION: USA


ParticipantsWHO PARTICIPATED: obese hypertensive patients

SETTING: clinic visits

MAIN INCLUSION CRITERIA: age > 18 years, BMI between 27 and 40 kg/m2, diagnosis of hypertension for at least 12 month before screening with adequate medical control (a constant dose of a calcium channel blocker for at least 60 days and stable dose of a single thiazide diuretic in addition was allowed): mean diastolic blood pressure ≤ 95 mm Hg during run-in period and variations in mean DBP measured at 3 consecutive run-in visits had to be within 10 mm Hg

MAIN EXCLUSION CRITERIA: secondary elevated blood pressure, pulse rate > 95/min at baseline, diastolic blood pressure > 95 mm Hg during run-in period, significant cardiac disease, endocrine abnormalities, severe cerebral trauma, stroke, substance abuse within 2 years before screening

GENERAL BASELINE CHARACTERISTICS (Sibutramine vs. Placebo)

NUMBER: 150 vs. 74 were randomized, 142 vs. 69 were analysed

MEAN AGE [YEARS]: 52 vs. 53

GENDER [% MALE]: 39% vs. 40%

NATIONALITY: Americans

ETHNICITY: 55% vs. 64% White, 39% vs. 30% African American, 7% vs. 6% others

WEIGHT [kg]: 97 vs. 96

BODY MASS INDEX [kg/m2]: 35 vs. 34 

MEAN SYSTOLIC BLOOD PRESSURE [mm Hg]: 134 vs. 134 

MEAN DIASTOLIC BLOOD PRESSURE [mm Hg]: 84 vs. 84

CO-MORBID CONDITIONS: -

ANTIHYPERTENSIVE TREATMENT. 100% (calcium channel blocker), 37% vs. 38% (diuretics), 3% vs. 4% (β-adrenergic receptor antagonists)

DURATION OF HYPERTENSION: for at least 12 months

 

SUBGROUP: African Americans


InterventionsINTERVENTION (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Sibutramine initial dosage of  5mg once daily titrated up to 20mg per day in 5-mg increments every 2 weeks, maintained at 20mg per day between weeks 8 and 52

CONTROL (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Placebo once a day

ADDITIONAL TREATMENT:

general dietary advice


OutcomesLENGTH OF FOLLOW-UP: 12 months

PRIMARY OUTCOMES:

1. MORTALITY: -

2. CARDIOVASCULAR MORBIDITY: -

3. ADVERSE EVENTS:

Definition: study related withdrawals and adverse events such as dry mouth and headache are reported.

 SECONDARY OUTCOMES:

1. CHANGES IN SYSTOLIC BLOOD PRESSURE [mm Hg]

Definition: mean change in systolic blood pressure

2. CHANGES IN DIASTOLIC BLOOD PRESSURE [mm Hg]

Definition: mean change in diastolic blood pressure

3. BODY WEIGHT [kg]

Definition: mean change in body weight

ADDITIONAL OUTCOMES MEASURED IN THE STUDY:

  1. Mean change in BMI (kg/m2)
  2. Quality of life parameters
  3. Changes in heart rate
  4. Mean change in waist / hip circumference
  5. Mean changes in lipid parameters, glucose and uric acid levels


NotesSPONSOR: Knoll Pharmaceutical Co, Mount Olive, (NJ) USA


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskOnly information was a 2:1 randomization ratio.

Allocation concealment (selection bias)Unclear riskMethod of concealment is not described.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskInsufficient information to permit any judgement.

Incomplete outcome data (attrition bias)
All outcomes
High riskQuote: "... statistical analyses were performed on an ITT basis ...last observation was carried forward (LOCF) ..."

The ITT population included all randomized patients who had at least one measurement after baseline.

 ----------------------------------------------------------------------    

WITHDRAWALS: 71 vs. 33 (Sibutramine vs. Placebo)

REASONS / DESCRIPTIONS (Sibutramine vs. Placebo)

- adverse events: 30 vs. 8

- no effects: 1 vs. 4

- withdrew consent: 3 vs. 4

- no follow up data: 10 vs. 1

- protocol violation: 10 vs. 5

- no further reasons mentioned: 17 vs. 11

Selective reporting (reporting bias)Unclear riskNo study protocol provided.

Other biasHigh risk1. The combination of a high withdrawal rate and the unknown length of stay of participants in the trial increases risk of bias even using the LOCF analysis.

2. It is unclear whether patients were comparable for prognostic factors at baseline.

McMahon 2002

MethodsDESIGN: parallel, randomized, double-blind

DURATION OF INTERVENTION: 12 months

NUMBER OF STUDY CENTRES: multicenter (numbers unclear)

COUNTRY OF PUBLICATION: USA


ParticipantsWHO PARTICIPATED: obese hypertensive patients treated with ACE-inhibitors

SETTING: outpatient clinic

MAIN INCLUSION CRITERIA: age ≥ 18 years, BMI ≥ 27 and ≤ 40 kg/m2, history of well-controlled hypertension for ≥ 60 days preceding the screening visit with a constant dose of an ACE inhibitor, with or without a thiazide diuretic (dose and nature unchanged for ≥ 60 days preceding the screening visit)

Well-controlled hypertension was protocol-defined as a mean supine diastolic blood pressure ≤ 95 mm Hg at each "qualifying" visit, with an overall difference of 10 mm Hg or less between visits, without changes to the dose of the ACE inhibitor or thiazide diuretic;

MAIN EXCLUSION CRITERIA: secondary elevated blood pressure, mean supine pulse rate > 95/min at baseline, mean supine diastolic blood pressure > 95 mm Hg at any run-in visit, significant cardiac disease, gastric surgery to reduce obesity, previous treatment with sibutramine

 

GENERAL BASELINE CHARACTERISTICS (Sibutramine vs. Placebo)

NUMBER: 146 vs. 74 were randomized, 84 vs. 36 were analysed

MEAN AGE [YEARS]: 52 vs. 51

GENDER [% MALE]: 42% vs. 43%

NATIONALITY: Americans

ETHNICITY: 80% vs. 87% Caucasians, 18% vs. 11% Blacks, 2% vs. 3% Mexican Americans, 1% vs. 0% Others

WEIGHT [kg]: 97 vs. 99

BODY MASS INDEX [kg/m2]: 34 vs. 34 

SUPINE SYSTOLIC BLOOD PRESSURE [mm Hg]: 129 vs. 129 

SUPINE DIASTOLIC BLOOD PRESSURE [mm Hg]: 82 vs. 83

CO-MORBID CONDITIONS: -

ANTIHYPERTENSIVE TREATMENT. 100% (ACE inhibitors), 49% vs. 55% (diuretics)

DURATION OF HYPERTENSION: controlled for ≥ 60 days

 

SUBGROUP: -


InterventionsINTERVENTION (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Sibutramine initial dosage of  5mg once daily in the morning titrated up to 20mg per day in 5-mg increments every 2 weeks, maintained at 20mg per day between weeks 8 and 52

CONTROL (ROUTE, TOTAL DOSE/DAY, FREQUENCY):

Placebo once daily in the morning

ADDITIONAL TREATMENT:

general dietary advice


OutcomesLENGTH OF FOLLOW-UP: 12 months

PRIMARY OUTCOMES:

1. MORTALITY: -

2. CARDIOVASCULAR MORBIDITY: -

3. ADVERSE EVENTS:

Definition: study related withdrawals and severe adverse events and symptoms such as dry mouth and headache are reported.

SECONDARY OUTCOMES:

1. CHANGES IN SYSTOLIC BLOOD PRESSURE [mm Hg]

Definition: change in systolic blood pressure from baseline

2. CHANGES IN DIASTOLIC BLOOD PRESSURE [mm Hg]

Definition: change in diastolic blood pressure from baseline

3. BODY WEIGHT [kg]

Definition: mean change in body weight

ADDITIONAL OTUCOMES MEASURED IN THE STUDY:

  1. Mean change in BMI (kg/m2)
  2. Change in heart rate
  3. Change in visceral fat mass
  4. Mean change in waist / hip circumference (cm)
  5. Mean changes in lipid parameters, glucose and uric acid levels
  6. Change in waist/hip ratio


NotesSPONSOR: Abbott Laboratories, Abbott Park, Illinois, USA


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskOnly information was a 2:1 randomisation ratio.

Allocation concealment (selection bias)Unclear riskMethod of concealment is not described.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskInsufficient information to permit any judgement.

Incomplete outcome data (attrition bias)
All outcomes
High riskQuote: "... statistical analyses were performed on an ITT basis ...last observation was carried forward (LOCF) ..."

The ITT population included all randomized patients who had efficacy measurements after baseline.

 ----------------------------------------------------------------------  

WITHDRAWALS: 62 vs. 38 (Sibutramine vs. Placebo)

REASONS / DESCRIPTIONS (Sibutramine vs. Placebo)

- adverse events: 23 vs. 4

- no effects: 1 vs. 6

- no follow up data: 1 vs. 2

- protocol violation: 6 vs. 5

 no further reasons mentioned: 31 vs. 21

Selective reporting (reporting bias)Unclear riskNo study protocol provided.

Other biasHigh risk1. The combination of a high withdrawal rate and the unknown length of participation in the trial increases risk of bias even using the LOCF analysis.

2. It is unclear whether patients were comparable for prognostic factors at baseline.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Bach 1999The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Bray 1999The study does not include participants with essential hypertension.

Broom 2002The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Davidson 1999The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

de Castro 2009

Derosa 2003The study does not include participants with essential hypertension.

Derosa 2008The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Derosa 2010

Despres 2005The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Despres 2009

Dujovne 2001The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Erdmann 2004The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Fanghaenel 2000The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Fanhaenel 2001The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Finer 2000The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Fujioka 2000The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Gentile 2005The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Ginsberg 2004The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Halpern 2002The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Halpern 2003The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Hauner 2004The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Hauptman 2000The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Heinonen 2009

Hollander 2007The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Hung 2005The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Jain 2011

James 1997The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

James 2000The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Kaukua 2004The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Kelley 2002The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Lindgarde 2000The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Lindgarde 2001The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Lindgarde 2001AThe study is not a randomized controlled trial.

Madsen 2009

McNulty 2003The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Miles 2002The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Nissen 2008

O'Leary 2011

Pathan 2004The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Patschan 2007The duration of the intervention is less than 24 weeks.

Pi-Sunyer 2006The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Reaven 2001The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Rossner 2000The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Rossner 2001The study is published in Swedish which is not among the languages prespecified for this report.

Samuelsson 2003The reported outcomes in this study are not relevant for this review.

Scheen 2002The study is not a randomized controlled trial.

SCOUT 2010

Sjostrom 1998The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Suyog 2011

Svendsen 2008

Swinburn 2005The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Tambascia 2003The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Tiikkainen 2004The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Triay 2012

Van Gaal 2005The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Van Gaal 2008The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Wirth 2001The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Zannad 2002The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

Zavoral 1998The study includes normotensive and hypertensive patients but does not report any or sufficient results for the hypertensive subgroup.

 
Comparison 1. Orlistat versus Placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Change in systolic blood pressure from baseline to endpoint42058Mean Difference (IV, Random, 95% CI)-2.46 [-4.01, -0.90]

 2 Change in diastolic blood pressure from baseline to endpoint42058Mean Difference (IV, Random, 95% CI)-1.92 [-2.99, -0.85]

 3 Change in body weight from baseline to endpoint42080Mean Difference (IV, Random, 95% CI)-3.73 [-4.65, -2.80]

 
Comparison 2. Sibutramine versus Placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Change in diastolic blood pressure from baseline to endpoint2428Mean Difference (IV, Fixed, 95% CI)3.16 [1.40, 4.92]

 2 Change in body weight from baseline to endpoint4574Mean Difference (IV, Fixed, 95% CI)-3.74 [-4.84, -2.64]

 
Table 1. Adverse events

StudyAdverse eventsResults

Orlistat vs. Placebo

Bakris

2002
total

thereof leading to withdrawal

serious

gastrointestinal

thereof leading to withdrawal

musculoskeletal
89% of P [O] vs. 71% of P [P], p<0.001

7% [O] vs. 7% [P]

14 P (12%) [O] vs. 15 P (9%) [P]

200 P (73%) [O] vs. 120 P (44%) [P], p<0.001

15 P (8%) [O] vs. 6 P (5%) [P]

23% of P [O] vs. 16% [P], p<0.05

Cocco

2005
total

serious

gastrointestinal
nr

0 P [O] vs. 0 P [P]

16 P (36%) [O]a vs. 11 P (24%) [P]a

Guy-Grand

2004
total

serious
nrb

nrb

XENDOS

2001-2006
total

leading to withdrawal

serious

gastrointestinal

musculoskeletal

nervous system

dermatological

vascular
99% of P [OD] vs. 96% of P [PD]

99% of P [OS] vs. 97% of P [PS]

9% of P [OD] vs. 4% of P [PD]

9% of P [OS] vs. 4% of P [PS]

18% of P [OD] vs. 12% of P [PD]

18% of P [OS] vs. 12% of P [PS]

93% of P [OD] vs. 70% of P [PD]

93% of P [OS] vs. 71% of P [PS]

65% of P [OD] vs. 62% of P [PD]

65% of P [OS] vs. 63% of P [PS]

39% of P [OD] vs. 39% of P [PD]

40% of P [OS] vs. 37% of P [PS]

20% of P [OD] vs. 17% of P [PD]

22% of P [OS] vs. 17% of P [PS]

17% of P [OD] vs. 19% of P [PD]

17% of P [OS] vs. 19% of P [PS]

Sibutramine vs. Placebo

Fanghaenel

2003
total

constipation

dizziness

dry mouth

headache

insomnia

restlessness
14 P (21 E) [S] vs. 13 P (20 E) [P]

4 P [S] vs. 2 P [P]

1 P [S] vs. 1 P [P]

4 P [S] vs. 2 P [P]

5 P [S] vs. 2 P [P]

1 P [S] vs. 1 P [P]

1 P [S] vs. 0 P [P]

Faria

2002-2005
total

dry mouth

arthralgia
nr

37% of P [S] vs. 9% of P [P], p<0.005

16% of P[S] vs. 2% of P [P], p=0.03

McMahon

2002
total

serious

treatment related

leading to withdrawal

(mostly hypertension)

dry mouth

headache
141 P (97%) [S] vs. 65 P (88%) [P]

9 P (6%) [S] vs. 5 P (7%) [P]

2 E [S] vs. 0 E [P]

23 P (16%) [S] vs. 4 P (5%) [P]

30 P (21%) [S] vs. 0 P [P]

41 P (28%) [S] vs. 17 P (23%) [P]

McMahon

2000
total

leading to withdrawal

(mostly hypertension)

dry mouth

headache

constipation

rash
nr

30 P (20%) [S] vs. 8 P (11%) [P]

29 P (19%) [S] vs. 2 P (3%) [P], p<0.05

37 P (25%) [S] vs. 21 P (28%) [P]

25 P (17%) [S] vs. 2 P (3%) [P], p<0.05

16 P (11%) [S] vs. 2 P (3%) [P]

 E: Events. nr: not reported. [O]: Orlistat. [OD]: Orlistat and diastolic blood pressure ≥ 90 mm Hg. [OS]: Orlistat and systolic blood pressure ≥140 mm Hg. P: Patients. [P]: Placebo. [PD]: Placebo and diastolic blood pressure ≥ 90 mm Hg. [PS]: Placebo and systolic blood pressure ≥ 140 mm Hg. [S]: Sibutramine.
a: No data on adverse events were reported for the whole study duration. The data above refer to 4 and 3 weeks of treatment in the orlistat and placebo group, respectively. After 3 months the number of patients with events decreased to 5(11%)[O] with flatulence and mild abdominal cramps vs 6(13%)[P] with nausea and hunger feeling.
b: Data are not available for the hypertensive subgroup, but only for the whole study population (withdrawal due to defecation troubles in 10 [O] vs. 2 [P] patients).
 
Table 2. Body weight

StudyBaselinea6 Moa12 Moa48 MoaChange

from baseline

to endpointa

Orlistat vs. Placebo

Bakris 2002b

Orlistat

Placebo
101 (1)c

102 (1)c
nr

nr
nr

nr
-

-
p<0.001

-5.4 (6.4)

-2.7 (6.4)

Cocco 2005

Orlistat

Placebo
107 (6)

106 (6)
102 (4)

104 (5)
-

-
-

-
p<0.001

-5.4d

-2.5d

Guy-Grand 2004

Orlistat

Placebo
94 (1)c

94 (1)c
nr

nr
-

-
-

-
p<0.0001

-5.8 (0.3)

-1.8 (0.2)

XENDOS 2001-2006

Orlistat [OD]

Placebo [PD]

Orlistat [OS]

Placebo [PS]
117 (18)

115 (18)

117 (17)

116 (18)
106 (17)

108 (18)

106 (17)

109 (18)
105 (18)

108 (19)

105 (17)

110 (19)
110 (19)

111 (20)

110 (18)

113 (19)
p<0.001

-6.6 (8.6)

-3.8 (7.8)

p<0.001

-6.8 (8.7)

-3.2 (7.4)

Sibutramine vs. Placebo

Fanghaenel 2003

Sibutramine

Placebo
75 (10)

78 (9)
70 (10)

75 (9)
-

-
-

-
significant

-5.5 (-3.8; -7.1)e

-3.4 (-1.9; -5.0)e

Faria 2002-2005

Sibutramine

Placebo
100 (19)

97 (14)
93 (18)

94 (15)
-

-
-

-
p<0.001

-6.8 (2.3) vs.

-2.4 (4.2);

McMahon 2002

Sibutramine

Placebo
97 (16)

99 (14)
nr

nr
nr

nr
-

-
p<0.05

-4.5

-0.4

McMahon 2000

Sibutramine

Placebo
97 (13)

96 (17)
nr

nr
nr

nr
-

-
p<0.05

-4.4

-0.5

 Mo: Months. nr: not reported. [O]: Orlistat. [OD]: Orlistat and diastolic blood pressure ≥ 90 mm Hg. [OS]: Orlistat and systolic blood pressure ≥140 mm Hg. P: Patients. [P]: Placebo. [PD]: Placebo and diastolic blood pressure ≥ 90 mm Hg. [PS]: Placebo and systolic blood pressure ≥ 140 mm Hg. [S]: Sibutramine. SD: Standard deviation.
a: Mean kg (SD), unless otherwise indicated.
b: Data are reported for 267 of 278 [O] and 265 of 276 [P] patients only.
c: Reported as being the standard deviation but probably the standard error due to its small number.
d: Published values are different but data were corrected after personal communication with the author.
e: 95% confidence interval.
 
Table 3. Systolic blood pressure

StudyBaselinea6 Moa12 Moa48 MoaChange

from baseline

to endpointa

Orlistat vs. Placebo

Bakris 2002b

Orlistat

Placebo
154 (13)

151 (13)
nr

nr
nr

nr
-

-
ns

-13.3 (15.2)

-11.0 (15.0)

Cocco 2005

Orlistat

Placebo
146 (10)

142 (6)
142 (13)

141 (9)
-

-
-

-
p=0.025

-4.3

-0.9

Guy-Grand 2004

Orlistat

Placebo
150 (1)c

152 (1)c
nr

nr
-

-
-

-
ns

-9.8 (1)

-9.8 (1)

XENDOS 2001-2006

Orlistat [OD]d

Placebo [PD]d

Orlistat [OS]d

Placebo [PS]d
146 (13)

146 (12)

149 (10)

149 (8)
135 (14)

136 (15)

125 (14)

138 (14)
135 (14)

138 (16)

135 (14)

140 (14)
137 (15)

139 (16)

138 (15)

140 (15)
p<0.024

-8.8 (14.8)

-6.4 (15.1)

p<0.002

-11.5 (14.9)

-8.6 (14.3)

Sibutramine vs. Placebo

Fanghaenel 2003e

Sibutramine

Placebo
139 (9)

139 (13)
125 (9)

123 (10)
-

-
-

-
ns

-13.9f

-16.5f

Faria 2002-2005

Sibutramine

Placebo
150 (18)

150 (15)
146 (15)

149 (22)
-

-
-

-
ns

-4.6f

-0.6f

McMahon 2002

Sibutramine

Placebo
129 (11)

129 (11)
nr

nr
133

130
-

-
p=0.0497

3.8

1.1

McMahon 2000

Sibutramine

Placebo
134 (10)

134 (11)
nr

nr
nr

nr
-

-
ns

2.7

1.5

 Mo: Months. nr: not reported. [O]: Orlistat. [OD]: Orlistat and diastolic blood pressure ≥ 90 mm Hg. [OS]: Orlistat and systolic blood pressure ≥140 mm Hg. P: Patients. [P]: Placebo. [PD]: Placebo and diastolic blood pressure ≥ 90 mm Hg. [PS]: Placebo and systolic blood pressure ≥ 140 mm Hg. [S]: Sibutramine. SD: Standard deviation.
a: Mean kg (SD), unless otherwise indicated.
b: Data are reported for 267 of 278 [O] and 265 of 276 [P] patients only.
c: Reported as being the standard deviation but probably the standard error due to its small number.
d: Based on LOCF-data on 399 [OD], 423 [PD], 493 [OS] and 504 [PS] patients.
e: Data at baseline were recorded after a 2-weeks washout-period of antihypertensiv drugs for diagnostic confirmation of hypertension.
f: Calculated.
 
Table 4. Diastolic blood pressure

StudyBaselinea6 Moa12 Moa48 MoaChange

from baseline

to endpointa

Orlistat vs. Placebo

Bakris 2002b

Orlistat

Placebo
98 (4)

98 (4)c
nr

nr
nr

nr
-

-
p=0.002

-11.4 (8.3)

-9.2 (8.4)

Cocco 2005

Orlistat

Placebo
88 (7)

85 (6)
84 (9)

85 (7)
-

-
-

-
p=0.012

-3.6

-0.8

Guy-Grand 2004

Orlistat

Placebo
97 (0)d

97 (0)d
nr

nr
-

-
-

-
ns

-7.5 (0.6)

-7.3 (0.6)

XENDOS 2001-2006

Orlistat [OD]e

Placebo [PD]e

Orlistat [OS]e

Placebo [PS]e
95 (6)

95 (5)

91 (9)

91 (8)
86 (8)

88 (9)

84 (9)

87 (9)
86 (8)

88 (10)

85 (9)

88 (10)
87 (9)

89 (10)

86 (9)

88 (10)
p<0.006

-8.1 (9.3)

-6.2 (9.9)

p<0.001

-5.0 (9.9)

-3.0 (10.4)

Sibutramine vs. Placebo

Fanghaenel 2003f

Sibutramine

Placebo
93 (7)

92 (8)
82 (5)

80 (5)
-

-
-

-
ns

-11.4g

-11.7g

Faria 2002-2005

Sibutramine

Placebo
91 (12)

94 (12)
92 (13)

92 (14)
-

-
-

-
ns

1.0g

-2.06g

McMahon 2002

Sibutramine

Placebo
82 (6)

83 (6)
nr

nr
86

83
-

-
p=0.004

3.0

-0.1

McMahon 2000

Sibutramine

Placebo
84 (5)

84 (6)
nr

nr
nr

nr
-

-
p<0.05

2.0

-1.3

 Mo: Months. nr: not reported. [O]: Orlistat. [OD]: Orlistat and diastolic blood pressure ≥ 90 mm Hg. [OS]: Orlistat and systolic blood pressure ≥140 mm Hg. P: Patients. [P]: Placebo. [PD]: Placebo and diastolic blood pressure ≥ 90 mm Hg. [PS]: Placebo and systolic blood pressure ≥ 140 mm Hg. [S]: Sibutramine. SD: Standard deviation.
a: Mean kg (SD), unless otherwise indicated.
b: Data are reported for 267 of 278 [O] and 265 of 276 [P] patients only.
c: The SD was published as being 35 but probably should be 3.5.
d: Reported as being the standard deviation but probably the standard error due to its small number.
e: Based on LOCF-data on 399 [OD], 423 [PD], 493 [OS] and 504 [PS] patients.
f: Data at baseline were recorded after a 2-weeks washout-period of antihypertensiv drugs for diagnostic confirmation of hypertension.
g: Calculated.