Sibutramine plus meal replacement therapy for body weight loss and maintenance in obese patients

Objective: Our objective was to assess the efficacy and safety of sibutramine with a low‐calorie diet (LCD) and commercial meal‐replacement product in achieving weight loss and weight‐loss maintenance in obese patients. Research Methods and Procedures: Eight U.S. centers recruited 148 obese patients for a 3‐month comprehensive weight‐loss therapy (Phase I) comprising daily sibutramine 10 mg + LCD (two Slim‐Fast meal‐replacement shakes, one low‐calorie meal; total kcal/d = 1200–1500). Patients (N = 113) who lost ≥5% of initial body weight during Phase I were randomized for a 9‐month period (Phase II) to daily sibutramine 15 mg + LCD (one meal‐replacement shake; two low‐calorie meals: total kcal/d ～1200–1500) or daily placebo + three low‐calorie meals (total kcal/d ～1200–1500). Both phases included behavior modification. Efficacy was assessed by body weight change during each phase and by the number of patients at endpoint maintaining ≥80% of the weight they had lost by the end of Phase I. Other outcomes included changes in cardiovascular and metabolic risk factors, adverse events, and vital signs. Results: Mean body weight change during Phase I was ?8.3 kg (p < 0.001). Patients randomized to sibutramine in Phase II had an additional ?2.5 kg mean weight loss vs. a 2.8‐kg increase in the placebo group (p < 0.001). More sibutramine patients maintained ≥80% of their Phase I weight loss at the end of Phase II (85.5% vs. placebo 36.7%, p < 0.001). Most adverse events were mild or moderate in severity, and all serious adverse events were unrelated to sibutramine. Discussion: Sibutramine plus LCD with meal replacements and behavior modification is a safe and effective strategy for achieving and sustaining weight loss in obese patients.     

Topiramate: Long‐Term Maintenance of Weight Loss Induced by a Low‐Calorie Diet in Obese Subjects

Objective: To examine the safety and efficacy of topiramate (TPM) for maintaining weight following a low‐calorie diet. Research Methods and Procedures: Obese subjects (30 ≤ BMI < 50 kg/m²) 18 to 75 years old received a low‐calorie diet for 8 weeks. Those who lost ≥8% of their initial weight received TPM (96 or 192 mg/d) or placebo; all were on a lifestyle modification plan. Sixty weeks of medication were planned. Sponsor ended study early to develop a new controlled‐release formulation with the potential to enhance tolerability and simplify dosing in this patient population. Efficacy was analyzed in subjects who completed 44 weeks of treatment before study termination. Results: Of the 701 subjects enrolled, 80% lost ≥8% of their initial body weight and were randomized; 293 were analyzed for efficacy. Most withdrawals were due to premature termination of the study. Subjects receiving TPM lost 15.4% (96 mg/d) and 16.5% (192 mg/d) of their enrollment weight by week 44, compared with 8.9% in the placebo group (p < 0.001). Subjects on TPM continued to lose weight after the run‐in, whereas those on placebo regained weight. Significantly more TPM subjects lost 5%, 10%, or 15% of their randomization weight than placebo. Most adverse events were related to the central nervous system. Discussion: During a treatment period of 44 weeks, TPM was generally well tolerated, and subjects maintained weight loss initially achieved by a low‐calorie diet—and produced additional clinically significant weight loss beyond that achieved by a low‐calorie diet.     

Fluoxetine: A Randomized Clinical Trial in the Maintenance of Weight Loss

Because current weight-reduction treatments have considerable recidivism, a therapy that could help patients maintain weight loss would be of benefit. A six-center, randomized, double-blind trial compared the effects of the specific serotonin uptake inhibitor, fluoxetine hydrochloride, and placebo on maintenance of weight loss. Obese outpatients who had lost ≤3.6 kg after 8 weeks of single-blind fluoxetine 60 mg/day in the qualification phase (N=317 [70.4% of patients entered]; mean ± standard deviation [SD] weight loss, 6.8 ± 2.8 kg) were randomly assigned to fluoxetine 20 mg/day (N=104), fluoxetine 60 mg/day (N=106), or placebo (N=107) for 40 weeks (maintenance phase). Patients received minimal nutrition/dietary counseling. Qualification phase clinic visits were biweekly; maintenance phase visits were monthly for 4 months, then bimonthly for 6 months. Patients treated with fluoxetine 60 mg/day continued to lose weight for 8 additional weeks (16 weeks total; maximum mean ± SD weight loss, 7.2 ± 4.6 kg); those treated with fluoxetine 20 mg/day or placebo began to regain weight. Mean weights remained below baseline values at week 48 (all groups); treatment differences were not statistically significant. Study completion rates were comparable (fluoxetine 20 mg/day, 67.3%; fluoxetine 60 mg/day, 56.6%; placebo, 67.3%; p = 0.175). Among commonly reported adverse events (>10% incidence), only asthenia was reported statistically significantly (p< 0.050) more frequently with fluoxetine than with placebo. Few patients discontinued for any single adverse event. Fluoxetine 60 mg/day was effective for a longer period than fluoxetine 20 mg/day or placebo in maintaining weight loss. Overall, fluoxetine was safe and well tolerated.     

Orlistat 60 mg reduces visceral adipose tissue: a 24-week randomized, placebo-controlled, multicenter trial

It is well established that abdominal obesity or upper body fat distribution is associated with increased risk of metabolic and cardiovascular disease. The purpose of the present study was to determine if a 24 week weight loss program with orlistat 60 mg in overweight subjects would produce a greater change in visceral adipose tissue (VAT) as measured by computed tomography (CT) scan, compared to placebo. The effects of orlistat 60 mg on changes in total fat mass (EchoMRI‐AH and BIA), ectopic fat (CT) and glycemic variables were assessed. One‐hundred thirty‐one subjects were randomized into a multicenter, double‐blind placebo controlled study in which 123 subjects received at least one post baseline efficacy measurement (intent‐to‐treat population). Both orlistat‐and placebo‐treated subjects significantly decreased their VAT at 24 weeks with a significantly greater loss of VAT by orlistat treated subjects (?15.7% vs. ?9.4%, P < 0.05). In addition, orlistat‐treated subjects had significantly greater weight loss (?5.93 kg vs. ?3.94 kg, P < 0.05), total fat mass loss (?4.65 kg vs. ?3.01 kg, P < 0.05) and trended to a greater loss of intermuscular adipose tissue and content of liver fat compared with placebo‐treated subjects. This is the first study to demonstrate that orlistat 60 mg significantly reduces VAT in addition to total body fat compared to placebo treated subjects after a 24 week weight loss program. These results suggest that orlistat 60 mg may be an effective weight loss tool to reduce metabolic risk factors associated with abdominal obesity.     

Effects of taspoglutide on glycemic control and body weight in obese patients with type 2 diabetes (T‐emerge 7 study)

Objective:

Therapies that lower blood glucose and provide weight loss may provide meaningful benefits for obese patients with type 2 diabetes mellitus (T2DM). This study assessed the efficacy of taspoglutide compared with placebo on glycemic control and weight in obese patients with T2DM inadequately controlled with metformin monotherapy.

Design and Methods:

In a 24‐week, randomized, double‐blind, placebo‐controlled, multicenter trial, obese adults with T2DM were randomized (1:1) to weekly subcutaneous taspoglutide 20 mg (10 mg for first 4 weeks) (n = 154) or placebo (n = 151) for 24 weeks. Efficacy measures included hemoglobin A1c (HbA1c) levels, body weight, percentage of patients achieving HbA1c ≤6.5 and ≤7.0%, and fasting plasma glucose (FPG). Adverse events (AEs) were assessed.

Results:

Mean baseline HbA1c was 7.55% and mean baseline BMI was 36.7 kg/m². HbA1c reductions from baseline were significantly greater with taspoglutide than placebo (least square mean [LSMean], ?0.81% vs. ?0.09%; P < 0.0001). Weight loss at week 24 was significantly greater with taspoglutide than placebo (LSMean, ?3.16 vs. ?1.85 kg; P < 0.01). In the taspoglutide and placebo groups, target HbA1c levels (≤6.5%) were achieved by 49 and 16% of patients, respectively, while 72 and 36% achieved HbA1c levels ≤7%. Decreases in FPG were significantly greater with taspoglutide than placebo (?23.59 vs. 0.09 mg/dl; P < 0.0001). Nausea and vomiting were the most common AEs associated with taspoglutide, but tended to be transient and generally mild or moderate.

Conclusions:

In obese patients with T2DM, once‐weekly taspoglutide provided the combined benefits of glycemic control and weight loss.

     

Weight Loss,Weight Maintenance,and Improved Cardiovascular Risk Factors after 2 Years Treatment with Orlistat for Obesity

Objective: To determine the effect of orlistat, a new lipase inhibitor, on long‐term weight loss, to determine the extent to which orlistat treatment minimizes weight regain in a second year of treatment, and to assess the effects of orlistat on obesity‐related risk factors. Research Methods and Procedures: This was a 2‐year, multicenter, randomized, double‐blind, placebo‐controlled study. Obese patients (body mass index 28 to 43 kg/m²) were randomized to placebo or orlistat (60 or 120 mg) three times a day, combined with a hypocaloric diet during the first year and a weight maintenance diet in the second year of treatment to prevent weight regain. Changes in body weight, lipid profile, glycemic control, blood pressure, quality of life, safety, and tolerability were measured. Results: Orlistat‐treated patients lost significantly more weight (p < 0.001) than placebo‐treated patients after Year 1 (6.6%, 8.6%, and 9.7% for the placebo, and orlistat 60 mg and 120 mg groups, respectively). During the second year, orlistat therapy produced less weight regain than placebo (p = 0.005 for orlistat 60 mg; p < 0.001 for orlistat 120 mg). Several obesity‐related risk factors improved significantly more with orlistat treatment than with placebo. Orlistat was generally well tolerated and only 6% of orlistat‐treated patients withdrew because of adverse events. Orlistat leads to predictable gastrointestinal effects related to its mode of action, which were generally mild, transient, and self‐limiting and usually occurred early during treatment. Discussion: Orlistat administered for 2 years promotes weight loss and minimizes weight regain. Additionally, orlistat therapy improves lipid profile, blood pressure, and quality of life.     

Effect of NPY5R antagonist MK-0557 on weight regain after very-low-calorie diet-induced weight loss

Objective: To evaluate whether MK‐0557, a highly selective, orally administered neuropeptide Y Y5 receptor antagonist, could limit weight regain after very‐low‐calorie diet (VLCD)‐induced weight loss. Research Methods and Procedures: We enrolled 502 patients 18 to 65 years of age with a BMI of 30 to 43 kg/m². Patients were placed on a VLCD (800 kcal/d liquid diet) for 6 weeks. Patients who lost ≥6% of initial body weight (n = 359) were randomized to 52 weeks of 1 mg/d MK‐0557 or placebo and maintained on a hypocaloric diet (300 kcal below weight maintenance requirements). Results: In randomized patients, the VLCD was associated with an average weight loss of 9.1 kg. After 12 weeks of double‐blind treatment, weight began to gradually increase for both placebo‐ and MK‐0557‐treated patients. The mean weight change (95% confidence interval) from baseline at the end of the VLCD to Week 52 was +3.1 (2.1, 4.0) and +1.5 (0.5, 2.4) kg for patients treated with placebo and MK‐0557, respectively. The difference of 1.6 kg between the two groups was significant (p = 0.014). Secondary endpoints, such as blood pressure, lipid profile, insulin, and leptin, as well as waist circumference and quality‐of‐life measurements, did not show significant differences between MK‐0557 and placebo treatments. Discussion: Although the difference in weight regain between placebo‐ and MK‐0557‐treated patients was statistically significant, the magnitude of the effect was small and not clinically meaningful. Antagonism of the neuropeptide Y Y5 receptor is not an efficacious treatment strategy for reducing weight regain after VLCD.     

A 6‐Month Randomized,Placebo‐Controlled,Dose‐Ranging Trial of Topiramate for Weight Loss in Obesity

Objective: To evaluate the efficacy and safety of topiramate (TPM) for weight loss in healthy obese subjects. Research Methods and Procedures: A randomized, double‐blind, placebo‐controlled, dose‐ranging trial was conducted. Three hundred eighty‐five subjects, 18 and 75 years of age, were randomized to receive either placebo or TPM at 64, 96, 192, or 384 mg daily. Dosing began at 16 mg once daily. In week 2, the dose was increased to 16 mg twice daily. Thereafter, the dose was raised every week by 32 mg/d (16 mg twice daily) until subjects reached their target dose. Twenty‐four weeks after beginning treatment, all subjects were tapered off treatment by a dose reduction of 50% per week. All participants received the same lifestyle program. Results: Mean percent weight loss from baseline to week 24 was ?2.6% in placebo‐treated patients vs. ?5.0%, ?4.8%, ?6.3%, and ?6.3% in the 64, 96, 192, and 384 mg/d TPM groups, respectively. Greater percentages of TPM‐treated patients lost at least 5% or 10% of body weight compared with placebo. The most frequent adverse events were related to the central or peripheral nervous system, including paresthesia, somnolence, and difficulty with memory, concentration, and attention. Most events were dose‐related, occurred early in treatment, and usually resolved spontaneously; only 21% receiving TPM withdrew due to adverse events compared with 11% on placebo. Discussion: TPM produced significantly greater weight loss than placebo at all doses.     

Improvement of Metabolism among Obese Breast Cancer Survivors in Differing Weight Loss Regimens

Objective: To compare the efficacy of different weight loss regimens on body weight loss and metabolic improvement in breast cancer survivors. Research Methods and Procedures: Forty‐eight obese breast cancer survivors were randomly divided into four groups and were followed for 1 year: 1) the Control group (subjects did not receive specific nutrition counseling); 2) the Weight Watchers group (subjects were given free coupons to attend weekly Weight Watchers meetings); 3) the Individualized group (a registered dietitian provided one‐on‐one nutritional counseling); and 4) the Comprehensive group (subjects received individualized dietary counseling and free coupons for the weekly Weight Watchers meetings). At baseline and 3‐, 6‐, and 12‐month data collection visits, a fasting blood sample was obtained for assays. A three‐day dietary record was kept during the week before these visits and dietary intake was analyzed. Results: Subjects in the three intervention groups lost weight (Control: 1.1 ± 1.7 kg; Weight Watchers: ?2.7 ± 2.1 kg; Individualized: ?8.0 ± 1.9 kg; Comprehensive: ?9.5 ± 2.7 kg) and percentage body fat, but only the Individualized and Comprehensive groups had significant losses. Subjects in the Comprehensive group showed the most improvement in cholesterol levels and had reductions in blood leptin levels. Discussion: Because insulin resistance and high blood leptin levels are associated with breast cancer, losing weight to improve these parameters may reduce the risk of recurrence. Only subjects in the Comprehensive group showed significant reductions in body weight and fat, energy intake, and leptin levels. For breast cancer survivors, different weight loss strategies should be considered to assist them in losing weight.     

A natural fiber complex reduces body weight in the overweight and obese: A double‐blind,randomized, placebo‐controlled study

Objective:

A proprietary natural fiber complex (Litramine IQP G‐002AS) derived from Opuntia ficus‐indica, and standardized on lipophilic activity, was previously shown in preclinical and human studies to reduce dietary fat absorption through gastrointestinal (GI) fat binding. Here, we investigated the efficacy and safety of IQP G‐002AS in body weight reduction.

Design and Methods:

One hundred twenty‐five overweight and obese adults participated in the study. Subjects were advised on physical activity, and received nutritional counseling, including hypocaloric diet plans (30% energy from fat and 500 kcal deficit/day). After a 2‐week placebo run‐in phase, subjects were randomized to receive either 3 g/day of IQP G‐002AS (IQ) or a placebo. The primary endpoint was change in body weight from baseline; secondary endpoints included additional obesity measures and safety parameters.

Results:

One hundred twenty‐three subjects completed the 12‐week treatment phase (intention‐to‐treat (ITT) population: 30 male and 93 female; mean BMI: 29.6 ± 2.8 kg/m² and age: 45.4 ± 11.3 years). The mean body weight change from baseline was 3.8 ± 1.8 kg in IQ vs. 1.4 ± 2.6 kg in placebo (P < 0.001). More IQ subjects lost at least 5% of their initial body weight compared to placebo (P = 0.027). Compared with placebo, IQ also showed significantly greater reduction in BMI, body fat composition, and waist circumference. IQ was well tolerated with no adverse reactions reported.

Conclusions:

These results suggest that the natural fiber complex Litramine IQP G‐002AS is effective in promoting weight loss.     

Body Weight Loss and Weight Maintenance in Relation to Habitual Caffeine Intake and Green Tea Supplementation

Objective: Investigation of the effect of a green tea‐caffeine mixture on weight maintenance after body weight loss in moderately obese subjects in relation to habitual caffeine intake. Research Methods and Procedures: A randomized placebo‐controlled double blind parallel trial in 76 overweight and moderately obese subjects, (BMI, 27.5 ± 2.7 kg/m²) matched for sex, age, BMI, height, body mass, and habitual caffeine intake was conducted. A very low energy diet intervention during 4 weeks was followed by 3 months of weight maintenance (WM); during the WM period, the subjects received a green tea‐caffeine mixture (270 mg epigallocatechin gallate + 150 mg caffeine per day) or placebo. Results: Subjects lost 5.9 ±1.8 (SD) kg (7.0 ± 2.1%) of body weight (p < 0.001). At baseline, satiety was positively, and in women, leptin was inversely, related to subjects’ habitual caffeine consumption (p < 0.01). High caffeine consumers reduced weight, fat mass, and waist circumference more than low caffeine consumers; resting energy expenditure was reduced less and respiratory quotient was reduced more during weight loss (p < 0.01). In the low caffeine consumers, during WM, green tea still reduced body weight, waist, respiratory quotient and body fat, whereas resting energy expenditure was increased compared with a restoration of these variables with placebo (p < 0.01). In the high caffeine consumers, no effects of the green tea‐caffeine mixture were observed during WM. Discussion: High caffeine intake was associated with weight loss through thermogenesis and fat oxidation and with suppressed leptin in women. In habitual low caffeine consumers, the green tea‐caffeine mixture improved WM, partly through thermogenesis and fat oxidation.     

Effect of a Dietary Herbal Supplement Containing Caffeine and Ephedra on Weight,Metabolic Rate,and Body Composition*

Objective: To evaluate the effect of a dietary supplement containing herbal caffeine (70 mg/dose) and ephedra (24 mg/dose; C&E) on metabolic rate, weight loss, body composition, and safety parameters. Research Methods and Procedures: In phase I, 12 healthy subjects with a BMI of 25 to 35 kg/m² had resting metabolic rate (RMR) measured for 2 hours after ingesting C&E or a placebo on two occasions 1 week apart, followed by a 1‐week washout before phase II. In phase II, these 12 and 28 additional subjects were randomized to a 12‐week, double‐blind trial comparing C&E (3 times/day) to placebo. In phase III, the C&E group was given open‐label C&E for 3 months, and the placebo group was given C&E for 6 months. Results: In phase I, C&E gave an average 8 ± 0.1% (SE) rise in RMR over 2 hours compared with placebo (p < 0.01). In phase II, weight loss at 12 weeks was 3.5 ± 0.6 kg with C&E compared with 0.8 ± 0.5 kg with placebo (p < 0.02). The percentage fat lost, shown by DXA, was 7.9 ± 2.9% with C&E and 1.9 ± 1.1% with placebo (p < 0.05). Pulse decreased more in the placebo group that in the C&E group (p < 0.03). There were no differences in lipid levels or blood pressure. In phase III, there was a 6‐month loss of 7.3% and 7.8% of initial body weight for the groups on placebo and C&E during phase II, respectively. There were no serious adverse events. Discussion: C&E increased RMR significantly by 8% compared with placebo, promoted more weight and fat loss than placebo, and was well tolerated.     

Promoting More Modest Weight Losses: A Pilot Study

Objective: This pilot study assessed the short‐ and long‐term effects of a modified cognitive behavioral treatment designed to facilitate obese patients’ acceptance of a 5% to 10% reduction in initial weight. Research Methods and Procedures: Participants were 17 women with a mean age of 46.5 ± 9.7 years and BMI of 34.7 ± 2.9 kg/m². They participated in a 40‐week program that included four phases. The first discussed the benefits of modest weight losses and the potential adverse effects of unrealistic expectations. Phase II provided instruction in traditional cognitive behavioral methods of weight control Phase III focused on methods to improve body image and self‐esteem. Phase IV addressed skills for weight maintenance. Changes in weight, self‐esteem, body image, and quality of life were assessed at the end of treatment and 1 year later (week 92). Results: At week 40, participants lost an average of 5.7 ± 5.3% of initial weight, which was associated with significant improvements in body image, self‐esteem, and quality of life. Improvements in psychosocial status were maintained at week 92, although mean weight loss at this time had declined to 2.9 ± 5.6% of initial weight. Increased satisfaction with body weight at week 40 was associated with significantly better maintenance of weight loss at follow‐up (r = ?0.70; p = 0.02). Discussion: Having participants seek only modest initial weight losses does not appear to facilitate weight maintenance. However, increasing patients’ satisfaction with their body weight at the end of treatment may help improve weight maintenance. More research is needed on the relation between satisfaction with initial weight loss and long‐term success.     

Effect of Pramlintide on Weight in Overweight and Obese Insulin‐Treated Type 2 Diabetes Patients

Objective: Several randomized, placebo‐controlled, double‐blind trials in insulin‐treated patients with type 2 diabetes have shown that adjunctive therapy with pramlintide reduces hemoglobin (Hb)A_1c with concomitant weight loss. This analysis further characterizes the weight‐lowering effect of pramlintide in this patient population. Research Methods and Procedures: This pooled post hoc analysis of two long‐term trials included all patients who were overweight/obese at baseline (BMI > 25 kg/m²), and who were treated with either 120 μg pramlintide BID (n = 254; HbA_1c 9.2%; weight, 96.1 kg) or placebo (n = 244; HbA_1c 9.4%; weight, 95.0 kg). Statistical endpoints included changes from baseline to week 26 in HbA_1c, body weight, and insulin use. Results: Pramlintide treatment resulted in significant reductions from baseline to week 26, compared with placebo, in HbA_1c and body weight (both, p < 0.0001), for placebo‐corrected reductions of ?0.41% and ?1.8 kg, respectively. Approximately three times the number of patients using pramlintide experienced a ≥5% reduction of body weight than with placebo (9% vs. 3%, p = 0.0005). Patients using pramlintide also experienced a proportionate decrease in total daily insulin use (r = 0.39, p < 0.0001). The greatest placebo‐corrected reductions in weight at week 26 were observed in pramlintide‐treated patients with a BMI >40 kg/m² and in those concomitantly treated with metformin (both, p < 0.001), for placebo‐corrected reductions of ?3.2 kg and ?2.5 kg, respectively. Discussion: These findings support further evaluation of the weight‐lowering potential of pramlintide in obese patients with type 2 diabetes.     

Effect of orlistat on eating behavior among participants in a 3-year weight maintenance trial

Objective: To examine the effect of orlistat on dietary restraint, disinhibition, hunger, and binge eating and to understand the relation between changes in eating behavior and weight maintenance. Methods and Procedures: Subjects were 306 women and men (age: 19–45 years; BMI: 37.5 ± 4.1 kg/m²) included in the Scandinavian Multicenter study of Obese subjects with the Metabolic Syndrome, a 3‐year clinical trial of orlistat or placebo following an 8‐week very low energy diet (VLED). Outcomes were changes in weight and in the Three Factor Eating Questionnaire (TFEQ) and Binge Eating Scale (BES) between screening and 17 and 33 months after randomization. As reported previously, weight gain following VLED was lower in subjects treated with orlistat than with placebo. Results: Compared to screening results, dietary restraint was increased and disinhibition, hunger, and binge eating were decreased in both groups. These changes were similar in both groups with the exception of the hunger score at month 33 that was reduced more in the placebo than in the orlistat group (difference between groups ?1.1 (95% CI (?2.0, ?0.2)) P = 0.014). In multivariate analyses, scores for restraint, disinhibition and binge eating were associated with weight loss after adjustment for BMI, gender, age, and treatment (all P ≤ 0.002, model R ² = 0.12–0.17). Discussion: Orlistat did not affect eating behavior differently in any substantial way than the placebo did in this long‐term weight maintenance trial. The results indicate that increased restraint and decreased disinhibition and binge eating are important for sustained weight maintenance in obese subjects with the metabolic syndrome.     

A two-year randomized weight loss trial comparing a vegan diet to a more moderate low-fat diet

Objective: The objective was to assess the effect of a low‐fat, vegan diet compared with the National Cholesterol Education Program (NCEP) diet on weight loss maintenance at 1 and 2 years. Research Methods and Procedures: Sixty‐four overweight, postmenopausal women were randomly assigned to a vegan or NCEP diet for 14 weeks, and 62 women began the study. The study was done in two replications. Participants in the first replication (N = 28) received no follow‐up support after the 14 weeks, and those in the second replication (N = 34) were offered group support meetings for 1 year. Weight and diet adherence were measured at 1 and 2 years for all participants. Weight loss is reported as median (interquartile range) and is the difference from baseline weight at years 1 and 2. Results: Individuals in the vegan group lost more weight than those in the NCEP group at 1 year [?4.9 (?0.5, ?8.0) kg vs. ?1.8 (0.8, ?4.3); p < 0.05] and at 2 years [?3.1 (0.0, ?6.0) kg vs. ?0.8 (3.1, ?4.2) kg; p < 0.05]. Those participants offered group support lost more weight at 1 year (p < 0.01) and 2 years (p < 0.05) than those without support. Attendance at meetings was associated with improved weight loss at 1 year (p < 0.001) and 2 years (p < 0.01). Discussion: A vegan diet was associated with significantly greater weight loss than the NCEP diet at 1 and 2 years. Both group support and meeting attendance were associated with significant weight loss at follow‐up.     

Calcium and Dairy Acceleration of Weight and Fat Loss during Energy Restriction in Obese Adults

Objective: Increasing 1, 25‐dihydroxyvitamin D in response to low‐calcium diets stimulates adipocyte Ca²⁺ influx and, as a consequence, stimulates lipogenesis, suppresses lipolysis, and increases lipid accumulation, whereas increasing dietary calcium inhibits these effects and markedly accelerates fat loss in mice subjected to caloric restriction. Our objective was to determine the effects of increasing dietary calcium in the face of caloric restriction in humans. Research Methods and Procedures: We performed a randomized, placebo‐controlled trial in 32 obese adults. Patients were maintained for 24 weeks on balanced deficit diets (500 kcal/d deficit) and randomized to a standard diet (400 to 500 mg of dietary calcium/d supplemented with placebo), a high‐calcium diet (standard diet supplemented with 800 mg of calcium/d), or high‐dairy diet (1200 to 1300 mg of dietary calcium/d supplemented with placebo). Results: Patients assigned to the standard diet lost 6.4 ± 2.5% of their body weight, which was increased by 26% (to 8.6 ± 1.1%) on the high‐calcium diet and 70% (to 10.9 ± 1.6% of body weight) on the high‐dairy diet (p < 0.01). Fat loss was similarly augmented by the high‐calcium and high‐dairy diets, by 38% and 64%, respectively (p < 0.01). Moreover, fat loss from the trunk region represented 19.0 ± 7.9% of total fat loss on the low‐calcium diet, and this fraction was increased to 50.1 ± 6.4% and 66.2 ± 3.0% on the high‐calcium and high‐dairy diets, respectively (p < 0.001). Discussion: Increasing dietary calcium significantly augmented weight and fat loss secondary to caloric restriction and increased the percentage of fat lost from the trunk region, whereas dairy products exerted a substantially greater effect.     

Bupropion SR Enhances Weight Loss: A 48‐Week Double‐Blind,Placebo‐ Controlled Trial

Objective: To critically examine the efficacy of bupropion SR for weight loss. Research Methods and Procedures: This 24‐week multicenter, double‐blind, placebo‐controlled study randomized obese adults to placebo, bupropion SR 300, or 400 mg/d. Subjects were counseled on energy‐restricted diets, meal replacements, and exercise. During a 24‐week extension, placebo subjects were randomized to bupropion SR 300 or 400 mg/d in a double‐blinded manner. Results: Of 327 subjects enrolled, 227 completed 24 weeks; 192 completed 48 weeks. Percentage losses of initial body weight for subjects completing 24 weeks were 5.0%, 7.2%, and 10.1% for placebo, bupropion SR 300, and 400 mg/d, respectively. Compared with placebo, net weight losses were 2.2% (p = 0.0468) and 5.1% (p < 0.0001) for bupropion SR 300 and 400 mg/d, respectively. The percentages of subjects who lost ≥5% of initial body weight were 46%, 59%, and 83% (p vs. placebo < 0.0001) for placebo, bupropion SR 300, and 400 mg/d, respectively; weight losses of ≥10% were 20%, 33%, and 46% (p vs. placebo = 0.0008) for placebo, bupropion SR 300, and 400 mg/d, respectively. Withdrawals, changes in pulse and blood pressure did not differ significantly from placebo at 24 weeks. Subjects who completed 48 weeks maintained mean losses of initial body weight of 7.5% and 8.6% for bupropion SR 300 and 400 mg/d, respectively. Discussion: Bupropion SR 300 and 400 mg/d were well‐tolerated by obese adults and were associated with a 24‐week weight loss of 7.2% and 10.1% and sustained weight losses at 48 weeks.     

Bupropion SR vs. Placebo for Weight Loss in Obese Patients with Depressive Symptoms

Objective: This randomized, double-blind, placebocontrolled study evaluated the efficacy and tolerability of bupropion sustained-release (bupropion SR) in reducing weight and depressive symptoms in obese adults. Research Methods and Procedures: Obese adults (body mass index, 30 to 44 kg/m²) not currently meeting criteria for major depression but with depressive symptoms (Beck Depression Inventory score 10–30) received bupropion SR 300 mg/d or placebo for 26 weeks with a 500 kcal/d-deficit diet. Patients who lost <5% of baseline weight at week 12 had bupropion SR dosage or placebo increased to 400 mg/d in a blinded fashion. Results: The bupropion SR group (n = 193) lost an average of 4.4 kg (4.6% of baseline weight) vs. 1.7 kg (1.8% of baseline weight) on placebo (n = 191, p < 0.001, last-observation-carried-forward analysis). More patients in the bupropion SR group than in the placebo group (40% vs. 16% of intent-to-treat sample, 50% vs. 28% of completers, respectively) lost at least 5% of baseline weight (p < 0.05 at week 4, p < 0.001 at weeks 6 to 26). The percentage of patients reporting ≥50% decrease in depressive symptoms did not differ between groups, but depressive symptoms improved more with bupropion SR than with placebo among patients with a history of major depression (p < 0.05, weeks 4 to 26). In the sample as a whole, improvement in depressive symptoms was related to weight loss of ≥5% regardless of treatment (p < 0.0001). Bupropion SR was well-tolerated. Discussion: Bupropion SR in combination with a 500 kcal/d-deficit diet facilitated weight loss. Weight loss of ≥5% may improve mood in obese patients with depressive symptoms.     

Sertraline and Relapse Prevention Training Following Treatment by Very-Low-Calorie Diet: A Controlled Clinical Trial

WADDEN, THOMAS A, SUSAN J BARTLETT, GARY D FOSTER, ROBERT A GREENSTEIN, BARBARA J WINGATE, ALBERT J STUNKARD AND KATHLEEN A LETIZIA. Sertraline and relapse prevention training following treatment by very-low-calorie diet: a controlled clinical trial. Obes Res. This study examined the combination of sertraline, a selective serotonin reuptake inhibitor, and relapse prevention training in the maintenance of weight loss following treatment by a very-low-calorie diet. A total of 53 women who had lost a mean (± SD) of 22.9 ± 7.1 kg from a pretreatment weight of 103.1 ± 17.8 kg were randomly assigned to a 54-week weight maintenance program that was combined with either: 1) 200 mg/d of sertraline; or 2) placebo. During the first 6 weeks, sertraline subjects lost significantly more weight and reported significantly greater reductions in hunger and preoccupation with food than did subjects on placebo. After this time, however, women in both conditions regained weight steadily. The 13 sertraline subjects who completed the 54-week study regained 17.7 ± 10.6 kg of their original 26.3 ± 7.6 kg loss, equal to a regain of 70.9 ± 41.7%. The 17 placebo completers regained 11.8 ± 9.0 kg of their 23.4 ± 7.8 kg loss, equal to a 46.5 ± 34.6% regain. End-of-treatment differences between groups in weight change were not statistically significant. Nor were there significant differences between the two conditions at any time in changes in fat-free mass, resting metabolic rate or dysphoria, all of which tended to increase with weight regain. The results are discussed in relation to findings from other long-term studies that combined diet and medication.