BMC Fam Pract. 2005 Jan
29;6(1):5.
Influence of intense multidisciplinary follow-up and orlistat on
weight reduction in a primary care setting.
Feigenbaum A, Pasternak S, Zusk E, Sarid M, Vinker S.
Department of Family Medicine, Sackler School of Medicine, Tel Aviv
University; Tel Aviv, Israel.
BACKGROUND: Obesity is the most common health problem in developed
countries. Recently, several physicians' organizations have issued
recommendations for treating obesity to family physicians, including
instructions in nutrition, physical activity and medications. The
aim of this study was to examine if effective weight-reducing treatment
can be given by a family physician. It compares regular treatment
with intensive treatment that include close follow-up and orlistat
treatment. METHODS: The study was conducted in three primary care
clinics. 225 patients were divided into three groups according to
their choice. Group A received a personal diet with fortnightly
meetings with the family physician and dietitian and orlistat treatment.
Group B received a general diet, monthly meetings with the family
physician only and orlistat treatment. Group C received a personal
diet, monthly meetings with the dietitian only and no drug treatment.
The primary endpoint was reduction of at least 5% of the initial
weight during the study period. RESULTS: A greater percentage of
patients in group A achieved their weight reduction goals than in
other groups (51%, 13% and 9% in groups A, B and C, respectively,
p < 0.001). There was a significant reduction in triglycerides
in all groups, a significant reduction of low density lipids (LDL)
in groups A and B and no significant difference in high density
lipids (HDL) in any group. CONCLUSIONS: Significant weight reduction
was obtained in a family physician setting. Further research is
needed to evaluate if, by providing the family physician with the
proper tools, similar success can be achieved in more clinics.
Int J Obes Relat Metab Disord. 2005 Mar 01.
Orlistat in responding obese type 2 diabetic patients: meta-analysis
findings and cost-effectiveness as rationales for reimbursement
in Sweden and Switzerland.
Ruof J, Golay A, Berne C, Collin C, Lentz J, Maetzel A.
[1] 1Health Services Research Unit, Division of Rheumatology,
Center of Internal Medicine, Hannover Medical School, Hannover,
Germany [2] 2Global Health Economics Department, Roche Pharmaceuticals,
Basel, Switzerland.
OBJECTIVE:: The aim of this study is to review the clinical and
economic rationale for the reimbursement of orlistat in responding
obese patients with type 2 diabetes. METHODS:: Data from seven
randomized controlled clinical trials of orlistat in overweight
and obese patients with type 2 diabetes were pooled. A subgroup
analysis involving patients who achieved a response (defined as
a weight loss of >/=5% after 12 weeks of treatment) was conducted.
The outcomes of the pooled analysis were then used to construct
a Markov health economic model covering an 11-y period. The incidences
of diabetes-related micro- and macrovascular complications were
derived from the United Kingdom Prospective Diabetes Study. The
effects of changes in body mass index, and the impact of micro-
and macrovascular complications on utilities were derived from
published sources. Publicly available cost data were used and
are presented here in 2001 Euros. Discounting of 3% was applied.
A probabilistic sensitivity analysis was conducted to examine
the robustness of results. RESULTS:: A total of 1249 patients
treated with orlistat and 1230 given placebo were eligible for
the intent-to-treat analysis. At the end of the study period,
23% of orlistat patients achieved a weight reduction of >/=5%.
These patients showed a mean decrease in HbA1C of 1.16%, a weight
reduction of 8.6 kg, a reduction in total cholesterol of 5.3%
and a reduction in systolic blood pressure of 5.2 mmHg. The base-case
economic analysis revealed costs per quality-adjusted life year
gained of \[euro]14 000 in Sweden and \[euro]13 600 in Switzerland.
CONCLUSION:: The data presented here support the utilization and
reimbursement of orlistat in overweight and obese diabetic patients
who respond to the treatment.International Journal of Obesity
advance online publication, 1 March 2005; doi:10.1038/sj.ijo.0802925.
Metabolism. 2004 Apr;53(4):430-4.
Modest weight loss and reduction in waist circumference after medical
treatment are associated with favorable changes in serum adipocytokines.
Valsamakis G, McTernan PG, Chetty R, Al Daghri N, Field A, Hanif
W, Barnett AH, Kumar S.
Department of Diabetes and Endocrinology, Birmingham Heartlands
Hospital, Birmingham, UK.
Modest weight loss if maintained is associated with significant
metabolic benefits and reduction in cardiovascular risk. Adipose
tissue secretes cytokines believed to contribute to the pathogenesis
of insulin resistance and cardiovascular risk. We therefore observed
the effect of modest weight loss on serum adipocytokines and their
relationship with changes in anthropometric and metabolic parameters
within a period of 6 months in the setting of a routine obesity
hospital clinic after various medical treatments. In this prospective,
nonrandomized, nonblinded observational study, patients were first
given treatment (sibutramine or orlistat) as decided by the treating
clinician and then allocated into 1 of 2 groups according to the
treatment prescribed. The first group included 21 Caucasian nondiabetic
female subjects, with a mean (+/-SD) age of 43 +/- 11 years and
a mean body mass index (BMI) of 46 +/- 8.6 kg/m(2); subjects were
treated with sibutramine 10 or 15 mg/d for weight loss. The second
group included 20 Caucasian nondiabetic female subjects, mean age
42 +/- 9 years and mean BMI 45.2 +/- 5.2 kg/m(2); orlistat was introduced
after 1 month on a low-fat (5%) after medical treatment in a routine
obesity hospital clinic is associated with improvements in insulin
sensitivity and lipid profile. Modest weight loss is also associated
with potentially favourably changes in serum adipocytokines, particularly
in a rise of serum adiponectin. Reduction of waist circumference
is associated with a change in serum resistin.
Cancer Res. 2004 Mar 15;64(6):2070-5.
Orlistat is a novel inhibitor of fatty acid synthase with antitumor
activity.
Kridel SJ, Axelrod F, Rozenkrantz N, Smith JW.
Cancer Research Center, The Burnham Institute, 10901 North Torrey
Pines Road, La Jolla, CA 92037, USA.
One of the fundamental principles of pharmacology is that most
drugs have side effects. Although considerable attention is paid
to detrimental side effects, drugs can also have beneficial side
effects. Given the time and expense of drug development, it would
be particularly exciting if a systematic method could be applied
to reveal all of the activities, including the unappreciated actions,
of a potential drug. The present study takes the first step along
this path. An activity-based proteomics strategy was used to simultaneously
identify targets and screen for their inhibitors in prostate cancer.
Orlistat, a Food and Drug Administration-approved drug used for
treating obesity, was included in this screen. Surprisingly, we
find a new molecular target and a potential new application for
Orlistat. Orlistat is a novel inhibitor of the thioesterase domain
of fatty acid synthase, an enzyme strongly linked to tumor progression.
By virtue of its ability to inhibit fatty acid synthase, Orlistat
halts tumor cell proliferation, induces tumor cell apoptosis,
and inhibits the growth of PC-3 tumors in nude mice.
Diabetes Care. 2004 Jan;27(1):155-61.
XENical in the prevention of diabetes in obese subjects (XENDOS)
study: a randomized study of orlistat as an adjunct to lifestyle
changes for the prevention of type 2 diabetes in obese patients.
Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L.
Department of Body Composition and Metabolism, Sahlgrenska University
Hospital, Goteborg, Sweden.
OBJECTIVE: It is well established that the risk of developing
type 2 diabetes is closely linked to the presence and duration
of overweight and obesity. A reduction in the incidence of type
2 diabetes with lifestyle changes has previously been demonstrated.
We hypothesized that adding a weight-reducing agent to lifestyle
changes may lead to an even greater decrease in body weight, and
thus the incidence of type 2 diabetes, in obese patients. RESEARCH
DESIGN AND METHODS: In a 4-year, double-blind, prospective study,
we randomized 3,305 patients to lifestyle changes plus either
orlistat 120 mg or placebo, three times daily. Participants had
a BMI >/=30 kg/m2 and normal (79%) or impaired (21%) glucose
tolerance (IGT). Primary endpoints were time to onset of type
2 diabetes and change in body weight. Analyses were by intention
to treat. RESULTS: Of orlistat-treated patients, 52% completed
treatment compared with 34% of placebo recipients (P < 0.0001).
After 4 years' treatment, the cumulative incidence of diabetes
was 9.0% with placebo and 6.2% with orlistat, corresponding to
a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated
that the preventive effect was explained by the difference in
subjects with IGT. Mean weight loss after 4 years was significantly
greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001)
and similar between orlistat recipients with impaired (5.7 kg)
or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second
analysis in which the baseline weights of subjects who dropped
out of the study was carried forward also demonstrated greater
weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001).
CONCLUSIONS: Compared with lifestyle changes alone, orlistat plus
lifestyle changes resulted in a greater reduction in the incidence
of type 2 diabetes over 4 years and produced greater weight loss
in a clinically representative obese population. Difference in
diabetes incidence was detectable only in the IGT subgroup; weight
loss was similar in subjects with IGT and or NGT.
Int J Obes Relat Metab Disord. 2003 Dec;27(12):1479-85.
Effects of a lipase inhibitor (Orlistat) on cholecystokinin and
appetite in response to a high-fat meal.
Goedecke JH, Barsdorf M, Beglinger C, Levitt NS, Lambert EV.
UCT/MRC Research Unit for Exercise Science and Sports Medicine,
Department of Human Biology, University of Cape Town, South Africa.
OBJECTIVE: To examine the short-term effects of a lipase inhibitor
(Orlistat) on physiological and behavioural measures of appetite
in response to a high-fat meal. DESIGN: Randomised, single blind,
placebo-controlled, crossover trial. SUBJECTS: A total of 19 healthy
nonobese male subjects. PROCEDURES: After an overnight fast, subjects
ingested a test meal of 2940 kJ (60% fat, 30% CHO, 10% protein)
with Orlistat (120 mg) or a placebo, separated by 2 weeks. Appetite,
as assessed by a standard line scale, and plasma cholecystokinin
(CCK) concentrations were measured prior to and every hour after
the test meal for 4 h. Thereafter, subjects ingested a quantified,
but self-selected portion of a standardised lunch (15% protein,
37% fat and 45% CHO), before completing a final line scale questionnaire.
RESULTS: The CCK response to the test meal was negatively correlated
with BMI in both the Orlistat and placebo trials (R=-0.69 and
-0.65, P<0.01). Orlistat administration did not significantly
alter the CCK response to the test meal (6.30+/-3.27 vs 7.36+/-3.94
pM min, for Orlistat and placebo, P=0.193). Similarly, the line
scale measures of appetite and subsequent intake (520+/-205 vs
554+/-197 g, P=0.48) were not different between the trials. CONCLUSION:
Orlistat administration did not alter short-term physiological
or behavioural measures of satiety in response to a high-fat meal
in healthy, nonobese subjects. The CCK response to a test meal
may be partly determined by BMI.
Prim Care. 2003 Jun;30(2):427-40.
Orlistat in the treatment of obesity.
Hollander P.
Baylor Hospital, Wadley Tower, Suite 656, 3600 Gaston Avenue,
Dallas, TX 75246, USA.
Orlistat has been well studied in several populations, including
patients who do and do not have type 2 diabetes and in patients
who have impaired glucose tolerance. Overall, modest, but significant,
weight loss was seen in all three groups of patients with favorable
effects on the comorbidities of obesity. Orlistat has not been
associated with a serious adverse event profile, and the mild
GI effects that are seen in some patients are well tolerated.
In obese patients who do not have diabetes, weight loss is achieved
and maintained as shown in the 2-year studies. Moreover, as was
well documented in the Swedish multi-morbidity study, favorable
treatment effects on the constituents of the metabolic syndrome
are seen. Orlistat, together with a hypocaloric diet, was proven
to be effective in preventing diabetes in patients who had impaired
glucose tolerance. The addition of orlistat resulted in significant
weight loss and significance decreases in levels of HbA1c in patients
who had type 2 diabetes who were treated with antihyperglycemic
drugs. Studies showed that it is possible to identify early which
patients may respond best to treatment. Orlistat offers an attractive
treatment option for obese patients who do and do not have diabetes
and as a combination drug for treatment of obese patients who
have type 2 diabetes.
Am J Gastroenterol. 2003 Apr;98(4):926-30.
Orlistat in the treatment of NASH: a case series.
Harrison SA, Ramrakhiani S, Brunt EM, Anbari MA, Cortese C, Bacon
BR.
Saint Louis University Liver Center, Division of Gastroenterology
and Hepatology, St. Louis, Missouri 63110, USA.
Nonalcoholic steatohepatitis is now recognized as a common chronic
liver disorder. Up to 16% of affected patients may progress to
cirrhosis. The incidence and prevalence of this disease are noted
to be increasing, in parallel with the nationwide increase in
obesity and diabetes. Treatment options for these patients remain
quite limited, however. Weight reduction has been advocated, but
there are little data to support this practice, as most patients
are unable to comply with the proper dietary modifications. We
report three obese patients with biopsy-proven nonalcoholic steatohepatitis
treated for 6-12 months with a weight reduction medication, orlistat,
who lost between 22-42 lb, and had significant clinical and histopathological
improvement on follow-up.
Int J Obes Relat Metab Disord. 2003 May;27(5):591-7.
Weight reduction and long-term maintenance after 18 months treatment
with orlistat for obesity.
Krempf M, Louvet JP, Allanic H, Miloradovich T, Joubert JM, Attali
JR.
CHU Hotel-Dieu, Service dEndocrinologie-Nutrition, Nantes, France.
OBJECTIVE: To determine the effect of orlistat on weight reduction
and the long-term maintenance of this weight loss when associated
with a continuous mildly reduced energy diet. DESIGN: A multicenter,
18-month, double-blind study conducted in 81 hospital centers.
Patients were randomized to orlistat 120 mg or placebo three times
daily in conjunction with a mildly reduced-energy diet maintained
throughout the study. SUBJECTS: In total, 696 otherwise healthy,
overweight patients aged 18-65 y (BMI >or=28 kg/m(2)) were
randomized to treatment with orlistat (n=346) or placebo (n=350).
MEASUREMENTS: Body weight, anthropometry, lipid and glycemic control
parameters and blood pressure. RESULTS: After 18 months, patients
treated with orlistat lost significantly more body weight compared
with placebo (-6.5+/-0.8 vs -3.0+/-0.8%; P=0.0005). After 12 months,
32.9% of orlistat vs 24.5% of placebo patients lost >or=10%
of their initial weight (P=0.04). A significantly greater number
of patients receiving orlistat treatment maintained this >or=10%
weight loss compared to those receiving placebo (28.1 vs 13.8%;
P<0.0001). Compared with placebo, orlistat was associated with
a greater decrease in fasting blood glucose (-0.86+/-0.12 vs -0.29+/-0.18
mmol/l; P<0.05) and LDL-cholesterol (-13.0+/-1.3 vs -7.0+/-1.3%;
P<0.001). CONCLUSION: A clinically meaningful reduction in
body weight and the maintenance of this weight loss is achievable
with orlistat treatment and dietary restriction over a period
of 18 months. This weight loss resulted in an improvement in risk
factors for coronary heart disease.
J Hypertens. 2002 Nov;20(11):2257-67.
Orlistat improves blood pressure control in obese subjects with
treated but inadequately controlled hypertension.
Bakris G, Calhoun D, Egan B, Hellmann C, Dolker M, Kingma I; orlistat
and resistant hypertension investigators.
Rush University Hypertension/Clinical Research Center, Department
of Preventive Medicine, Rush Presbyterian/St. Lukes Medical Center,
Chicago, Illinois, USA.
OBJECTIVE: To investigate the hypothesis that weight reduction
with orlistat plus mild caloric restriction leads to better blood
pressure control than diet alone in obese individuals with inadequately
controlled hypertension.DESIGN This was a 1-year, prospective,
randomized, double-blind, placebo-controlled, multicenter trial
of orlistat plus diet versus placebo plus diet in obese hypertensives.
INTERVENTIONS: Participants were randomized to receive either
orlistat or placebo; all received a 600 kcal deficient diet with
no more than 30% of calories from fat. Weight and blood pressure,
lipid levels and fasting glucose and insulin levels were followed.
MAIN OUTCOME MEASURES: Patients on orlistat experienced greater
weight loss (-5.4 +/- 6.4 versus -2.7 +/- 6.4 kg, P< 0.001)
and greater reduction in body mass index (-1.9 +/- 2.3 versus
-0.9 +/- 2.2 kg/m2, P<0.001). Target weight loss, defined as
> or= 5% body weight (BW), was obtained in more orlistat-treated
patients than in the placebo group (46 versus 23%, P<0.001).
Diastolic BP decreased more in orlistat-treated patients than
in the placebo group (-11.4 +/- 8.3 versus -9.2 +/- 8.4 mmHg,
P = 0.002). A greater percentage of orlistat-treated patients
reached goal diastolic blood pressure (BP), defined as final diastolic
BP< 90 mmHg or a reduction of at least 10 mmHg (67 versus 53%,
P< 0.001). The orlistat-treated group had significantly greater
reductions in total cholesterol ( P<0.001), low-density lipoprotein
cholesterol (P = 0.001) and non-high-density lipoprotein cholesterol
(P< 0.005) and target 30% cardiovascular risk reduction was
obtained in more orlistat-treated patients (36.1 versus 24.0%,
P< 0.04). CONCLUSION: A weight-loss program with orlistat is
more effective than diet alone to lower blood pressure and results
in greater cardiovascular risk reduction.
Int J Clin Pract. 2002 Sep;56(7):494-9.
Randomised trial of the effect of orlistat on body weight and
cardiovascular disease risk profile in obese patients: UK Multimorbidity
Study.
Broom I, Wilding J, Stott P, Myers N; UK Multimorbidity Study
Group.
Department of Clinical Biochemistry, University of Aberdeen and
Grampian University Hospitals Trust, UK.
The potential effect of orlistat on cardiovascular co-morbidities
may have been previously underestimated. This study assesses the
efficacy of orlistat therapy for weight loss and cardiovascular
risk factor reduction in obese patients with cardiovascular risk.
This was a 54-week, double-blind, randomised, placebo-controlled,
parallel group study with 531 patients being randomised. Mean
weight loss was significantly greater with orlistat than with
placebo (5.8% vs 2.3%; p<0.0001). Orlistat was also associated
with significantly greater improvements than placebo in diastolic
BP (-5.5 vs -3.1 mmHg; p<0.01), systolic blood pressure (-6.0
vs -2.3 mmHg; p<0.01), oral glucose tolerance test (-0.37 vs
+0.09 mmol/l; p<0.05), fasting glucose (-0.19 vs +0.06 mmol/l;
p<0.05), total cholesterol (-1.31% vs +3.78%; p<0.0001),
LDL-cholesterol (-7.09% vs -0.55%; p<0.0001) and waist circumference
(-5.99 vs -2.60 cm; p<0.0001). Orlistat was well tolerated.
Orlistat weight loss is associated with improvements in cardiovascular
co-morbidities, and hence cardiovascular risk.
Diabetes Care. 2002 Jun;25(6):1033-41.
Clinical efficacy of orlistat therapy in overweight and obese
patients with insulin-treated type 2 diabetes: A 1-year randomized
controlled trial.
Kelley DE, Bray GA, Pi-Sunyer FX, Klein S, Hill J, Miles J, Hollander
P.
Montifiore Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
15213, USA.
OBJECTIVE; Weight loss improves glycemic control, lipid profiles,
and blood pressure in patients with type 2 diabetes. However,
successful long-term weight loss is difficult for these patients,
particularly those treated with insulin. The aim of this study
was to assess the effect of orlistat, a gastrointestinal lipase
inhibitor, on weight loss, glycemic control, and cardiovascular
risk factors in overweight or obese insulin-treated type 2 diabetic
patients. RESEARCH DESIGN AND METHODS: This study was a 1-year
multicenter, randomized, double-blind, placebo-controlled trial
of orlistat (120 mg three times a day) or placebo combined with
a reduced-calorie diet in overweight or obese adults (BMI 28-40
kg/m(2)) with type 2 diabetes treated with insulin alone or combined
with oral agents, but with suboptimal metabolic control (HbA(1c)
7.5-12.0%). Outcome measurements included changes in body weight,
glycemic control, blood pressure, and serum lipids. RESULTS; After
1 year, the orlistat group lost significantly more weight (-3.89
+/- 0.3% of baseline body weight, means +/- SE) than the placebo
group (-1.27 +/- 0.3%, P < 0.001). Orlistat treatment, compared
with placebo, produced greater decreases in HbA(1c) (-0.62 +/-
0.08 vs. -0.27 +/- 0.08%, P = 0.002), fasting serum glucose (-1.63
+/- 0.3 vs. -1.08 +/- 0.3 mmol/l, P = 0.02), and the required
doses of insulin and other diabetic medications. Orlistat also
produced greater improvements than placebo in serum total cholesterol
(P = 0.0002) and LDL cholesterol concentrations (P = 0.001) and
LDL/HDL ratio (P = 0.01). CONCLUSIONS; Orlistat therapy produces
clinically significant weight loss, with improvements in glycemic
control and cardiovascular disease risk factors, in overweight
or obese patients with type 2 diabetes who have suboptimal metabolic
control with insulin therapy.
Obes Res. 2001 Oct;9(10):599-604.
Orlistat inhibits dietary cholesterol absorption.
Mittendorfer B, Ostlund RE Jr, Patterson BW, Klein S.
Department of Internal Medicine and Center for Human Nutrition,
Washington University School of Medicine, St. Louis, Missouri
63110, USA.
OBJECTIVE: Orlistat decreases the absorption of dietary triglycerides
by inhibiting intestinal lipases. Orlistat therapy is associated
with a greater decline in plasma low-density lipoprotein-cholesterol
concentrations than that expected from weight loss alone. Therefore,
we evaluated the effect of orlistat treatment on dietary cholesterol
absorption as a possible mechanism for the independent effect
of orlistat on plasma cholesterol concentration. RESEARCH METHODS
AND PROCEDURES: Cholesterol absorption from a standardized meal,
containing 72 mg of cholesterol, was determined in 18 subjects
with class II abdominal obesity (BMI, 35.0 to 39.9 kg/m(2)) by
simultaneous administration of intravenous ([(2)H(6)] cholesterol)
and oral ([(2)H(5)] cholesterol) cholesterol tracers. In protocol
1 (n = 9), cholesterol absorption was determined on two different
occasions, 10 to 20 days apart, to assess the reproducibility
of the tracer method. In protocol 2 (n = 9), cholesterol absorption
was determined with and without orlistat therapy in a prospective,
randomized, crossover design to assess the effect of orlistat
on cholesterol absorption. RESULTS: In protocol 1, cholesterol
absorption from the test meal was the same on both occasions (53
+/- 5% and 51 +/- 5%). In protocol 2, orlistat treatment caused
a 25% reduction in cholesterol absorption, from 59 +/- 6% to 44
+/- 5% (p < 0.01). DISCUSSION: These data demonstrate that
orlistat inhibits dietary cholesterol absorption, which may have
beneficial effects on lipoprotein metabolism in obese subjects
that are independent of weight loss itself.
Control Clin Trials. 2001 Oct;22(5):515-25.
Principles for enhanced recruitment of subjects in a large clinical
trial. the XENDOS (XENical in the prevention of Diabetes in Obese
Subjects) study experience.
Torgerson JS, Arlinger K, Kappi M, Sjostrom L.
Department of Body Composition and Metabolism, Sahlgrenska University
Hospital, Goteborg, Sweden.
In most clinical trials it is problematic to recruit enough patients
within a reasonable time period. Prolonged or inefficient recruitment
or both can have negative scientific and economic consequences.
The XENDOS (XENical in the prevention of Diabetes in Obese Subjects)
study is an ongoing randomized, double-blind, placebo-controlled,
prospective, multicenter trial investigating whether orlistat
combined with hypocaloric diet and moderate physical exercise
can reduce the incidence of diabetes in obese subjects. To implement
the XENDOS protocol and recruit the study patients, we designed
a system for centralized patient recruitment and centralized scheduling
of patients and staff at the 22 collaborating centers. The recruitment
and inclusion phase was divided into a series of different consecutive
examinations of increasing complexity. Relatively simple initial
examinations enabling a large throughput of patients were followed
by more detailed examinations of fewer subjects, by then known
to fulfil some of the study-specific requirements. With the aid
of object-oriented techniques, the software was modularized to
enable concurrent engineering. We also selected a structure where
plug-in modules handling specific tasks could be added to the
system as needed. The design was supported by a flow-oriented
view of the progress of the patients through the study. With this
overall solution we managed to include 3305 subjects (98.8% of
the requested number) within less than 4 months. The sex distribution
(44.8% men) and the number of patients with impaired glucose tolerance
(IGT), (21.1%) were in close accordance with, or far better than,
the requirements of the protocol (45% men, at least 10% IGT patients).
The basic design of the XENDOS information system can be adapted
to fulfil the requirements of other study protocols within the
fields of obesity, diabetes, hypertension, coronary heart disease,
etc. Shortening the recruitment and inclusion phase of large clinical
trials is of great value both to be medical society and the pharmaceutical
industry.
Obes Rev. 2000 Oct;1(2):121-6.
Orlistat for the treatment of obesity: rapid review and cost-effectiveness
model.
Foxcroft DR, Milne R.
School of Health Care, Oxford Brookes University, UK.
The aim of this study is to clarify the potential benefits, disbenefits
and costs of Orlistat for the treatment of obesity. The method
was a search for relevant systematic reviews and randomized controlled
trials, in Medline, Pre-Medline, Embase and the Cochrane Library,
using Orlistat and its synonyms. Identified trials were appraised
using a standard appraisal checklist and trial data were extracted
for use in cost-effectiveness modelling. Three large multicentre,
randomized placebo controlled trials were included in the rapid
review. On average, Orlistat results in obese people losing an
additional 3-4% of their initial body weight over diet alone during
a 2 year period. There was no strong evidence that this short-term
weight loss would have a longer-term impact on morbidity and mortality.
The cost utility of Orlistat treatment was estimated at around
46,000 Pounds per Quality Adjusted Life Year gained (extreme values
sensitivity analysis 14,000 Pounds to 132,000 Pounds). This rapid
review raises some important questions about the potential value
of Orlistat in the treatment of obesity. Further research is needed,
not only to clarify the longer-term impact of Orlistat treatment,
but also to uncover the longer-term impact on mortality and morbidity
from short-term weight loss.
Heart Dis. 2000 Mar-Apr;2(2):174-81.
Orlistat.
Wong NN, Cheng-Lai A.
Department of Pharmacy and Family Medicine, Montefiore Medical
Center, 111 East 210th Street, Bronx, NY 10467, USA.
Obesity is a risk factor for cardiovascular disease. Orlistat
is a gastric and pancreatic lipase inhibitor indicated for the
management of obesity. It is the first antiobesity agent that
is not a centrally acting appetite suppressant; instead, it decreases
absorption of dietary fat in the gastrointestinal tract. The effects
of orlistat on weight loss, weight regain, and on a number of
obesity-related risk factors have been assessed in large clinical
trials of 1 to 2 years' duration. Compared with subjects who received
placebo and a hypocaloric diet alone, weight loss of at least
5 to 10% of initial body weight was observed in a significantly
larger number of subjects who were treated with orlistat plus
a hypocaloric diet during the first year of treatment. Subjects
who received orlistat 120 mg three times daily regained significantly
less weight than subjects who received placebo during the second
year of treatment. In addition, orlistat was found to have favorable
effects on blood pressure and concentrations of serum lipid, glucose,
and insulin. Gastrointestinal events are the most common adverse
effects experienced by patients who received orlistat; however,
most of these events were mild to moderate in intensity, transient
in duration, and decreased considerably during the second year
of treatment.
Rev Med Brux. 1999 Jun;20(3):159-63.
Orlistat (Xenical).
Crenier L, Sternon J.
Service dEndocrinologie, Hopital Erasme et C.U.M.G.-U.L.B.
Orlistat, a potent inhibitor of the pancreatic and intestinal
lipases, is the first member of a new therapeutic class approved
for the treatment of obesity. Its administration with fat-containing
foods results in a partial inhibition of triglyceride hydrolysis
in the digestive lumen and subsequent reduction of the free fatty
acids and monoglycerides absorption. At the usual dosage of 120
mg tid, about 30% of ingested fat are excreted non digested in
feces. When administered with a mildly hypocaloric diet, orlistat
contributes to loss of weight by a additional caloric deficit
and promotes further compliance of the obese patient to the dietary
recommendations. Several double-blinded, placebo-controlled studies
have shown a statistically significant loss of weight of about
10% when orlistat was prescribed with a well balanced, mildly
hypocaloric diet to obese patients during one year. Moreover,
small but significant beneficial changes in the serum lipid levels
occurred in these patients. Because the orlistat molecule is not
reabsorbed, its side effects are mostly due to the gastrointestinal
effects and consist in steatorhea after fatty meals. However,
the treatment is generally well tolerated. Since the recent withdrawal
from the worldwide market of the anorectic agents, phentermine
and fenfluramine, orlistat is at this time the only drug approved
by the European Community for the treatment of obesity. However,
its long-term value are not currently known.
Rev Med Liege. 1999 Mar;54(3):192-6.
Pharmacy-clinics medication of the month. Orlistate (xenical).
Scheen AJ, Ernest P, Letiexhe MR.
Service de Diabetologie, Nutrition et Maladies metaboliques, Universite
de Liege.
Orlistat (tetrahydrolipstatin), launched by Roche under the trade
name Xenical, is a selective inhibitor of pancreatic and gastro-intestinal
lipases. It reduces the digestion of dietary fat and its resorption
through digestive mucosa by around 30%. It is indicated, at a
dose of 3 x 120 mg/day (one dose with each meal) and together
with a moderately low-calorie and low-fat diet, for the treatment
of obesity. It has been shown, in placebo-controlled two-year
trials, to almost double the number of obese subjects who succeed
in loosing at least 10% of initial body weight. Independently,
it contributes to decrease serum cholesterol levels by 6-10%.
Because of its mechanism of action, this drug can induce intestinal
side-effects which tend to decrease with time and with the reduction
of fat intake, thus improving diet compliance.
