Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients

Sjöström, Lars; Rissanen, Aila; Andersen, T; Boldrin, Mark; Golay, Alain; Koppeschaar, H. P. F.; Krempf, Michel

doi:10.1016/s0140-6736(97)11509-4

Cited by 1,016 publications

(718 citation statements)

References 13 publications

Supporting

Mentioning

647

Contrasting

Unclassified

Order By: Relevance

“…The magnitude of absolute weight loss observed over this treatment period was comparable to that reported for orlistat, [8][9][10]12,13 sibutramine 14,15 and rimonabant. 16,17 The magnitude of absolute weight loss in the placebo group was similar to that reported for orlistat trials, but greater than that in sibutramine and rimonabant trials, which reflects the greater dietary support given to patients in the lipase inhibitor studies.…”

Section: Discussionsupporting

confidence: 78%

“…These include oily spotting, flatus with discharge, oily evacuation and faecal incontinence, which can reduce patient compliance and withdrawal from treatment. [8][9][10] Cetilistat is a novel highly lipophilic benzoxazinone that inhibits GI and pancreatic lipases, which raises the possibility of a distinct clinical profile, and is in development for the management of obese patients with or without complications. In Phase I clinical trials in healthy volunteers, cetilistat increased faecal fat excretion and was well tolerated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cetilistat (ATL-962), a novel lipase inhibitor: a 12-week randomized, placebo-controlled study of weight reduction in obese patients

et al. 2006

View full text Add to dashboard Cite

Objective: To determine the efficacy, safety and tolerability of cetilistat (ATL-962), a novel inhibitor of gastrointestinal (GI) lipases, in obese patients. Design: Phase II, multicentre, randomized, placebo-controlled, parallel group study. Enrolled patients (N ¼ 442) were advised a hypocaloric diet (deficient by 500 kcal per day, 30% of calories from fat) for a 2-week run-in period. Patients who satisfied the entry criteria (N ¼ 371) continued on the hypocaloric diet and were randomized to either placebo or one of three different doses of cetilistat (60 mg three times daily t.i.d., 120 mg t.i.d. and 240 mg t.i.d.) for 12 weeks, followed by a 4-week post-treatment follow-up. Safety, tolerability and body weight were assessed, together with other parameters associated with obesity. Outcome measures: The primary outcome measure was absolute change in body weight from baseline. Secondary outcomes included the proportion of patients achieving pre-defined weight loss targets, changes from baseline in waist circumference and in blood lipids. GI tolerability criteria were specifically assessed, as was safety. Results: Treatment with cetilistat reduced mean body weight to similar extents at all doses, which were statistically significant compared with placebo (60 mg t.i.d. 3.3 kg, Po0.03; 120 mg t.i.d. 3.5 kg, P ¼ 0.02; 240 mg t.i.d. 4.1 kg, Po0.001). Total serum and low-density lipoprotein cholesterol levels were likewise significantly reduced by 3-11% at all doses of cetilistat. Cetilistat was well tolerated. The frequency of withdrawal owing to treatment-emergent adverse events was similar between cetilistat-treated groups (5.3-7.6%) and placebo (7.6%). Adverse events were generally mild to moderate in intensity, occurred on only one occasion and were mostly GI in nature. The incidence of GI adverse events was increased in the cetilistat-treated groups compared to placebo. However, those GI adverse events, such as flatus with discharge and oily spotting, only occurred in 1.8-2.8% of subjects in the cetilistat-treated groups. Conclusions: Cetilistat produced a clinically and statistically significant weight loss in obese patients in this short-term 12-week study. This was accompanied by significant improvements in other obesity-related parameters. Cetilistat treatment was well tolerated. The risk-benefit demonstrated in this study in terms of weight loss vs intolerable GI adverse effects shows that cetilistat merits further evaluation for the pharmacotherapy of obesity and related disorders.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Cetilistat (ATL-962), a novel lipase inhibitor: a 12-week randomized, placebo-controlled study of weight reduction in obese patients

et al. 2006

View full text Add to dashboard Cite

show abstract

“…72 No significant effect on blood pressure compared with dietary/lifestyle-only therapy occurred, except in two studies, one of which involved subjects Long-term efficacy of weight loss methods JD Douketis et al with poorly controlled hypertension. 62,71 Orlistat had inconsistent effects on glycemic control: modest but significantly greater reductions in fasting blood glucose (0.1-1.7 mmol/l) than diet-only therapy in six studies, [60][61][62][63]67,68 but no difference in two studies. 65,66 The greatest improvements in glycemic control occurred in subjects with type 2 diabetes.…”

Section: Jd Douketis Et Almentioning

confidence: 99%

Systematic review of long-term weight loss studies in obese adults: clinical significance and applicability to clinical practice

et al. 2005

View full text Add to dashboard Cite

BACKGROUND: Obesity is a common health problem that requires a long-term care approach. We systematically reviewed long-term (Z2 y) studies investigating dietary/lifestyle, pharmacologic, and surgical weight loss methods to assess (1) weight loss efficacy, defined by absolute weight loss and the proportion of subjects with Z5% weight loss, (2) effects of weight loss on cardiovascular risk factors, and (3) applicability of findings from studies to everyday clinical practice. METHODS: The MEDLINE, HealthSTAR, and the Cochrane Controlled Trials databases were searched for studies investigating the long-term efficacy of weight loss methods in overweight and obese adults. Data were extracted for (i) weight loss after 1 y (pharmacologic studies only), 2 y, 3 y, and 4 y, (ii) proportion of subjects with Z5% weight loss at the end of follow-up, and (iii) changes (end-of follow-up minus baseline values) in blood lipids, fasting blood glucose, and systolic and diastolic blood pressure. RESULTS: Dietary/lifestyle therapy provides o5 kg weight loss after 2-4 y, pharmacologic therapy provides 5-10 kg weight loss after 1-2 y, and surgical therapy provides 25-75 kg weight loss after 2-4 y. Weight loss of Z5% baseline weight is not consistently associated with improvements in cardiovascular risk factors and these benefits appear to be intervention specific and occur mainly in people with concomitant cardiovascular risk factors. Weight loss studies have methodologic limitations that restrict the applicability of findings to unselected obese people assessed in everyday clinical practice. These limitations include an inadequate study duration, large proportions of subjects lost to follow-up, a lack of an appropriate usual care group, and a lack of reporting of outcomes in high-risk subgroups. CONCLUSIONS: Dietary/lifestyle and pharmacologic weight loss interventions provide modest weight loss, and may improve markers of cardiovascular risk factors although these benefits occur mainly in patients with cardiovascular risks. Studies investigating weight loss have methodologic limitations that restrict the applicability of findings to obese patients assessed in clinical practice.

show abstract

“…19,20 In clinical trials orlistat treatment was associated with gastrointestinal adverse events including oily spotting from the rectum (27%), flatus with discharge (24%), faecal Safety profile of orlistat NV Acharya et al urgency (22%) and faecal incontinence (8%). 5,6 In this study, diarrhoea was the most frequently reported gastrointestinal event with 4.9% (789) of patients reported to have experienced this event during treatment. The other gastrointestinal events described above were each reported in o1% of patients in this study: flatulence (122; 0.8%); faecal incontinence (86; 0.5%) rectal discharge (77; 0.5%).…”

Section: Discussionmentioning

confidence: 64%

“…4 Published studies have shown that treatment with orlistat improves many outcome measures such as decrease in cholesterol and LDL cholesterol levels, lowering of both systolic and diastolic blood pressure and finally improvement in glycaemic control and reductions in cardiovascular risk factors in patients with Type 2 diabetes. 5,6 Postmarketing surveillance is essential because the safety database on newly licensed drugs is limited by both the number and characteristics of the patients involved in prelaunch clinical studies. 7 The Drug Safety Research Unit (DSRU) provides a postmarketing drug surveillance scheme, which monitors the safety of newly marketed drugs during their immediate postmarketing period in England, using the observational cohort technique of prescription-event monitoring (PEM).…”

Section: Introductionmentioning

confidence: 99%

Safety profile of orlistat: results of a prescription-event monitoring study

2006

View full text Add to dashboard Cite

Introduction: Orlistat, the first of a new class of drugs for the treatment of obesity, was launched in the UK in December 1998. The prescribing information recommends that treatment with orlistat should be discontinued after 12 weeks if the patient has not achieved a specified loss of weight. Objective: To monitor the safety of orlistat prescribed in the primary care setting in England using prescription-event monitoring (PEM). Methods: A postmarketing surveillance study using the observational cohort technique of PEM. Patients were identified from dispensed prescriptions issued by primary care physicians for orlistat between December 1998 and November 1999. The outcome data were event reports obtained by sending questionnaires (green forms) to the prescribing doctor at least 6 months after the first prescription for an individual patient. Incidence densities, expressed as number of first reports of an event/1000 patient-months of exposure, were calculated. Significant differences between incidence densities (IDs) for events reported in the 1st month (ID 1 ) and months 2 and 3 (ID 2-3 ) of exposure were regarded as potential signals. Reasons for stopping orlistat were analysed. Follow-up information was requested for selected events and used to assess the causal association with orlistat. Results: Green forms containing clinically useful information on 16 021 patients (median age 45 years (interquartile range 35-54); 80.1% females) were received. The events reported most frequently during the 1st month of treatment were 'not effective' (639; 4.0% of cohort), diarrhoea (371; 2.3%) and weight loss (230; 1.4%). Twelve clinical adverse events were identified for which ID 1 was significantly greater than ID 2-3 . These included non-specific events (e.g. intolerance, malaise/ lassitude, unspecified side effects), weight loss and vaginitis/vulvitis. The remaining events were gastrointestinal in nature and included diarrhoea, pain abdomen, flatulence, nausea/vomiting, rectal discharge, faecal incontinence and 'gastrointestinal unspecified' events. A similar pattern of predominately gastrointestinal events was seen for reasons for stopping and suspected adverse drug reactions. Review of selected events for causality revealed 45 events which were assessed as possibly or probably related to orlistat. Conclusions: This study shows that orlistat is fairly well tolerated. The safety profile of orlistat was similar to the prescribing information and experience reported in the literature.

show abstract

Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients

Cited by 1,016 publications

References 13 publications

Cetilistat (ATL-962), a novel lipase inhibitor: a 12-week randomized, placebo-controlled study of weight reduction in obese patients

Cetilistat (ATL-962), a novel lipase inhibitor: a 12-week randomized, placebo-controlled study of weight reduction in obese patients

Systematic review of long-term weight loss studies in obese adults: clinical significance and applicability to clinical practice

Safety profile of orlistat: results of a prescription-event monitoring study

Contact Info

Product

Resources

About