Weight Control and Risk Factor Reduction in Obese Subjects Treated for 2 Years With Orlistat

Davidson, Michael; Hauptman, Jonathan; DiGirolamo, Mario; Foreyt, John P.; Halsted, Charles H.; Heber, David; Heimburger, Douglas C.; Lucas, Charles; Robbins, David C.; Chung, Jain; Heymsfield, Steven B.

doi:10.1001/jama.281.3.235

Cited by 850 publications

(705 citation statements)

References 23 publications

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“…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%

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

et al. 2006

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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.

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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

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“…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

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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.

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“…It is well known that obesity can worsen the metabolic abnormalities often associated with DM including hyperinsulinemia, hyperglycemia, hypertension, and hyperlipidemia (Colditz et al, 1990;Chan et al, 1994;Ford et al, 1997;Maggio & Pi-Sunyer, 1997). A modest 5-10% weight loss in obese nondiabetic individuals has been shown to result in marked improvements in some of these metabolic disturbances (Wing et al, 1987;Goldstein, 1992;Davidson et al, 1999;Hollander et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Long-term efficacy of soy-based meal replacements vs an individualized diet plan in obese type II DM patients: relative effects on weight loss, metabolic parameters, and C-reactive protein

et al. 2004

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Background: Achieving significant weight loss and glycemic control in diabetic patients remains a challenging task. Objective: This study compared the effects of a soy-based meal replacement (MR) plan vs an individualized diet plan (IDP; as recommended by the American Diabetes Association) on weight loss and metabolic profile. Design/Subjects: A total of 104 subjects were randomized prospectively to the two treatments for a total of 12 months. Results: In all, 77 of the 104 subjects completed the study. Percentage weight loss in MR group (4.5770.81%) was significantly greater (Po0.05) than in IDP group (2.2570.72%). Fasting plasma glucose was significantly reduced in MR group (126.474.9 mg/dl) compared with IDP group (152.576.6 mg/dl, Po0.0001) at 6 months but not at 12 months. Controlling for baseline levels, hemoglobin Alc level improved by 0.4970.22% for those receiving MR when compared to IDP group (Po0.05). A greater number of subjects in MR group reduced their use of sulfonylureas (Po0.0001) and metformin (Po0.05) as compared to IDP group. High-sensitivity C-reactive protein (hs-CRP) decreased À26.3% (P ¼ 0.019) in MR group compared to À7.06% (P ¼ 0.338) in IDP group at 6 months. Similar changes were observed at 12 months with MR groups, with hs-CRP decreasing by À25.0% (P ¼ 0.019) compared to À18.7% (P ¼ 0.179) in IDP group. Conclusion: This study demonstrates that MR is a viable strategy for weight reduction in diabetic patients, resulting in beneficial changes in measures of glycemic control and reduction of medications.

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Weight Control and Risk Factor Reduction in Obese Subjects Treated for 2 Years With Orlistat

Cited by 850 publications

References 23 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

Long-term efficacy of soy-based meal replacements vs an individualized diet plan in obese type II DM patients: relative effects on weight loss, metabolic parameters, and C-reactive protein

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