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.     

Body Composition and Hormonal Adaptations Associated with Forskolin Consumption in Overweight and Obese Men

Objective: This study examined the effect of forskolin on body composition, testosterone, metabolic rate, and blood pressure in overweight and obese (BMI ≥ 26 kg/m²) men. Research Methods and Procedure: Thirty subjects (forskolin, n = 15; placebo, n = 15) were studied in a randomized, double‐blind, placebo‐controlled study for 12 weeks. Results: Forskolin was shown to elicit favorable changes in body composition by significantly decreasing body fat percentage (BF%) and fat mass (FM) as determined by DXA compared with the placebo group (p ≤ 0.05). Additionally, forskolin administration resulted in a change in bone mass for the 12‐week trial compared with the placebo group (p ≤ 0.05). There was a trend toward a significant increase for lean body mass in the forskolin group compared with the placebo group (p = 0.097). Serum free testosterone levels were significantly increased in the forskolin group compared with the placebo group (p ≤ 0.05). The actual change in serum total testosterone concentration was not significantly different among groups, but it increased 16.77 ± 33.77% in the forskolin group compared with a decrease of 1.08 ± 18.35% in the placebo group. Discussion: Oral ingestion of forskolin (250 mg of 10% forskolin extract twice a day) for a 12‐week period was shown to favorably alter body composition while concurrently increasing bone mass and serum free testosterone levels in overweight and obese men. The results indicate that forskolin is a possible therapeutic agent for the management and treatment of obesity.     

A randomized,phase 3 trial of naltrexone SR/bupropion SR on weight and obesity‐related risk factors (COR‐II)

Objective:

To examine the effects of naltrexone/bupropion (NB) combination therapy on weight and weight‐related risk factors in overweight and obese participants.

Design and Methods:

CONTRAVE Obesity Research‐II (COR‐II) was a double‐blind, placebo‐controlled study of 1,496 obese (BMI 30‐45 kg/m²) or overweight (27‐45 kg/m² with dyslipidemia and/or hypertension) participants randomized 2:1 to combined naltrexone sustained‐release (SR) (32 mg/day) plus bupropion SR (360 mg/day) (NB32) or placebo for up to 56 weeks. The co‐primary endpoints were percent weight change and proportion achieving ≥5% weight loss at week 28.

Results:

Significantly (P < 0.001) greater weight loss was observed with NB32 versus placebo at week 28 (?6.5% vs. ?1.9%) and week 56 (?6.4% vs. ?1.2%). More NB32‐treated participants (P < 0.001) experienced ≥5% weight loss versus placebo at week 28 (55.6% vs. 17.5%) and week 56 (50.5% vs. 17.1%). NB32 produced greater improvements in various cardiometabolic risk markers, participant‐reported weight‐related quality of life, and control of eating. The most common adverse event with NB was nausea, which was generally mild to moderate and transient. NB was not associated with increased events of depression or suicidality versus placebo.

Conclusion:

NB represents a novel pharmacological approach to the treatment of obesity, and may become a valuable new therapeutic option.

     

Randomized controlled trials of the D1/D5 antagonist ecopipam for weight loss in obese subjects

Objective: To evaluate the efficacy and safety of the selective dopamine D1/D5 antagonist ecopipam for the treatment of obesity. Research Methods and Procedures: Four randomized, double‐blind, multicenter trials compared ecopipam (n = 1667) and placebo (n = 1118) in obese subjects including type 2 diabetic subjects. Subjects received oral ecopipam 10, 30, or 100 mg daily for 12 weeks (Phase 2) or 50 or 100 mg daily for 52 weeks (Phase 3) combined with a weight loss program. Primary efficacy variables were the proportion of subjects with ≥5% weight loss from baseline at 12 weeks (Phase 2) or the distribution of percentage weight loss from baseline at 52 weeks (Phase 3). Results: In the Phase 2 study, 26% of subjects administered ecopipam 100 mg vs. 6% of placebo subjects achieved ≥5% weight loss after 12 weeks (p < 0.01). In the Phase 3 studies, ecopipam 100 mg produced a 3.1% to 4.3% greater weight loss than placebo at 52 weeks. More subjects administered ecopipam vs. placebo achieved a 5% to 10% or >10% weight loss in two non‐diabetic phase 3 trials. Ecopipam‐treated subjects also maintained more weight loss compared with placebo subjects at 52 weeks. Phase 3 studies were discontinued because of unexpected psychiatric adverse events (ecopipam 31% vs. placebo 15%), including depression, anxiety, and suicidal ideation. Discussion: Ecopipam was effective for achieving and maintaining weight loss in obese subjects, including type 2 diabetic subjects; however, the adverse effects on mood observed in the Phase 3 studies exclude its projected use in weight management.     

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.     

Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease

Objective: Tesofensine (TE) is a norepinephrine, dopamine, and serotonin reuptake inhibitor. We conducted a meta‐analysis of TE's effect on body weight in trials investigating its potential for treatment of Parkinson's or Alzheimer's disease. Methods and Procedures: Four randomized, double‐blind, multicenter trials compared TE (n = 740) and placebo (n = 228), two in each disease. Patients received oral TE or placebo once daily for 14 weeks without any weight loss program. Results were adjusted for baseline values, age, and study. Results: In the placebo group, 14% were obese and 21% were in the TE group. In the total cohort, weight change after 14 weeks was +0.5, ?0.5, ?0.9, ?1.8, ?2.8% in the placebo, 0.125, 0.25, 0.5 and 1.0 mg in the TE groups, respectively (P = 0.015 for dose effect). In the obese subgroup, weight changes were ?0.2, ?1.7, ?1.6, ?1.5, ?3.7%, and 2.1, 8.2, 14.1, 20.9, 32.1% of the obese patients achieved ≥5% weight loss (P < 0.001 for 0.25, 0.5, and 1.0 mg vs. placebo for both end points). Changes in heart rate were ?0.4, 2.1, 4.2, 6.0, and 6.8 bpm after 14 weeks (TE vs. placebo: P < 0.001 from 0.25 mg), but no effect on blood pressure was observed. Discussion: TE produced a placebo‐subtracted weight loss of ～4% for >14 weeks without any diet and lifestyle therapy, which is similar to that of sibutramine, but with no effect on blood pressure. On the basis of these results, TE is now being developed for obesity management.     

Enhanced Weight Loss With Pramlintide/Metreleptin: An Integrated Neurohormonal Approach to Obesity Pharmacotherapy

The neurohormonal control of body weight involves a complex interplay between long‐term adiposity signals (e.g., leptin), and short‐term satiation signals (e.g., amylin). In diet‐induced obese (DIO) rodents, amylin/leptin combination treatment led to marked, synergistic, fat‐specific weight loss. To evaluate the weight‐lowering effect of combined amylin/leptin agonism (with pramlintide/metreleptin) in human obesity, a 24‐week, randomized, double‐blind, active‐drug‐controlled, proof‐of‐concept study was conducted in obese or overweight subjects (N = 177; 63% female; 39 ± 8 years; BMI 32.0 ± 2.1 kg/m²; 93.3 ± 13.2 kg; mean ± s.d.). After a 4‐week lead‐in period with pramlintide (180 µg b.i.d. for 2 weeks, 360 µg b.i.d. thereafter) and diet (40% calorie deficit), subjects achieving 2–8% weight loss were randomized 1:2:2 to 20 weeks of treatment with metreleptin (5 mg b.i.d.), pramlintide (360 µg b.i.d.), or pramlintide/metreleptin (360 µg/5 mg b.i.d.). Combination treatment with pramlintide/metreleptin led to significantly greater weight loss from enrollment to week 20 (?12.7 ± 0.9%; least squares mean ± s.e.) than treatment with pramlintide (?8.4 ± 0.9%; P < 0.001) or metreleptin (?8.2 ± 1.3%; P < 0.01) alone (evaluable, N = 93). The greater reduction in body weight was significant as early as week 4, and weight loss continued throughout the study, without evidence of a plateau. The most common adverse events with pramlintide/metreleptin were injection site events and nausea, which were mostly mild to moderate and decreased over time. These results support further development of pramlintide/metreleptin as a novel, integrated neurohormonal approach to obesity pharmacotherapy.     

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.     

Using facebook and text messaging to deliver a weight loss program to college students

Objective:

Between 31 and 35% of the college‐aged population is overweight or obese, yet few weight loss trials for this population have been conducted. This study examined the feasibility, acceptability, and initial efficacy of a technology‐based 8‐week weight loss intervention among college students.

Design and Methods:

Students (N = 52) were randomly assigned to one of the three arms: Facebook (n = 17); Facebook Plus text messaging and personalized feedback (n = 18); Waiting List control (n = 17), with assessments at 4 weeks and 8 weeks (post‐treatment). Participants were 20.47 ± 2.19 years old, 86.45 ± 17.11 kg, with a body mass index of 31.36 ± 5.3 kg/m². Participants were primarily female (86.5%), and the sample was racially diverse (57.7% Caucasian, 30.8% African American, 5.8% Hispanic, and 5.7% other races).

Results:

The primary outcome was weight loss after 8 weeks (post‐treatment); 96.0% of the participants completed this assessment. At 8 weeks, the Facebook Plus group had significantly greater weight loss (?2.4 ± 2.5 kg) than the Facebook (?0.63 ± 2.4 kg) and Waiting List (?0.24 ± 2.6 kg) (both Ps < 0.05). Weight change at 8 weeks was not significantly different between the Facebook and Waiting List groups.

Conclusions:

Results show preliminary efficacy and acceptability of the two active intervention arms (97.0% found the program helpful, 81.3% found the videos/handouts helpful, and 100% would recommend the program to others). Results indicate the potential for an innovative weight loss intervention that uses technology platforms (Facebook and text messaging) that are frequently used and already integrated into the cultural life of college students.

     

Effects of Two Conjugated Linoleic Acid Isomers on Body Fat Mass in Overweight Humans

Objective: To examine the effects of two different conjugated linoleic acid (CLA) isomers at two different intakes on body composition in overweight humans. Research Methods and Procedures: Eighty‐one middle‐aged, overweight, healthy men and women participated in this bicentric, placebo‐controlled, double‐blind, randomized study. For 6 weeks (run‐in period), all subjects consumed daily a drinkable dairy product containing 3 g of high oleic acid sunflower oil. Volunteers were then randomized over five groups receiving daily either 3 g of high oleic acid sunflower oil, 1.5 g of cis‐9, trans‐11 (c9t11) CLA, 3 g of c9t11 CLA, 1.5 g of trans‐10, cis‐12 (t10c12) CLA, or 3 g of t10c12 CLA administrated as triacylglycerol in a drinkable dairy product for 18 weeks. Percentage body fat mass and fat and lean body mass were assessed at the end of the run‐in and experimental periods by DXA. Dietary intake was also recorded. Results: Body fat mass changes averaged 0.1 ± 0.9 kg (mean ± SD) in the placebo group and ?0.3 ± 1.4, ?0.8 ± 2.1, 0.0 ± 2.3, and ?0.9 ± 1.7 kg in the 1.5‐g c9t11, 3‐g c9t11, 1.5‐g t10c12, and 3‐g t10c12 groups, respectively. Changes among the groups were not significantly different (p = 0.444). Also, lean body mass and dietary intake were not significantly different among the treatments. Discussion: A daily consumption of a drinkable dairy product containing up to 3 g of CLA isomers for 18 weeks had no statistically significant effect on body composition in overweight, middle‐aged men and women.     

Weight loss strategies for obese adults: personalized weight management program vs. standard care

Objective: The objective of this study was to evaluate the effect of a 32‐week personalized Polar weight management program (PWMP) compared with standard care (SC) on body weight, body composition, waist circumference, and cardiorespiratory fitness in overweight or obese adults. Research Methods and Procedures: Overweight or obese (29 ± 2 kg/m²) men and women (n = 74) 38 ± 5 years of age were randomly assigned into either PWMP (men = 20, women = 21) or SC (men = 15, women = 18). Both groups managed their own diet and exercise program after receiving the same standardized nutrition and physical activity advice. PWMP also received a weight management system with literature to enable the design of a personalized diet and exercise weight loss program. Body weight and body composition, waist circumference, and cardiorespiratory fitness were measured at weeks 0, 16, and 32. Results: Eighty percent of participants completed the 32‐week intervention, with a greater proportion of the dropouts being women (PWMP: 2 men vs. 7 women; SC: 2 men vs. 4 women). At 32 weeks, PWMP completers had significantly (p < 0.001) greater losses in body weight [6.2 ± 3.4 vs. 2.6 ± 3.6 (standard deviation) kg], fat mass (5.9 ± 3.4 vs. 2.2 ± 3.6 kg), and waist circumference (4.4 ± 4.5 vs. 1.0 ± 3.6 cm). Weight loss and fat loss were explained by the exercise energy expenditure completed and not by weekly exercise duration. Discussion: More effective weight loss was achieved after treatment with the PWMP compared with SC. The results suggest that the PWMP enables effective weight loss through tools that support self‐monitoring without the requirement of more costly approaches to program supervision.     

Weight Loss With Naltrexone SR/Bupropion SR Combination Therapy as an Adjunct to Behavior Modification: The COR‐BMOD Trial

This 56‐week, randomized, placebo‐controlled trial examined the efficacy and safety of naltrexone plus bupropion as an adjunct to intensive behavior modification (BMOD). A total of 793 participants (BMI = 36.5 ± 4.2 kg/m²) was randomly assigned in a 1:3 ratio to: (i) placebo + BMOD (N = 202); or (ii) naltrexone sustained‐release (SR, 32 mg/day), combined with bupropion SR (360 mg/day) plus BMOD (i.e., NB32 + BMOD; N = 591). Both groups were prescribed an energy‐reduced diet and 28 group BMOD sessions. Co‐primary end points were percentage change in weight and the proportion of participants who lost ≥5% weight at week 56. Efficacy analyses were performed on a modified intent‐to‐treat population (ITT; i.e., participants with ≥1 postbaseline weight while taking study drug (placebo + BMOD, N = 193; NB32 + BMOD, N = 482)). Missing data were replaced with the last observation obtained on study drug. At week 56, weight loss was 5.1 ± 0.6% with placebo + BMOD vs. 9.3 ± 0.4% with NB32 + BMOD (P < 0.001). A completers analysis revealed weight losses of 7.3 ± 0.9% (N = 106) vs. 11.5 ± 0.6% (N = 301), respectively (P < 0.001). A third analysis, which included all randomized participants, yielded losses of 4.9 ± 0.6 vs. 7.8 ± 0.4%, respectively (P < 0.001). Significantly more NB32 + BMOD‐ vs. placebo + BMOD‐treated participants lost ≥5 and ≥10% of initial weight, and the former had significantly greater improvements in markers of cardiometabolic disease risk. NB32 + BMOD was generally well tolerated, although associated with more reports of nausea than placebo + BMOD. The present findings support the efficacy of combined naltrexone/bupropion therapy as an adjunct to intensive BMOD for obesity.     

Decreased Glucagon‐like Peptide 1 Release after Weight Loss in Overweight/Obese Subjects

Objective: Postprandial glucagon‐like peptide 1 (GLP‐1) release seems to be attenuated in obese subjects. Results on whether weight loss improves GLP‐1 release are contradictory. The aim of this study was to further investigate the effect of weight loss on basal and postprandial GLP‐1 release in overweight/obese subjects. Research Methods and Procedures: Thirty‐two overweight/obese subjects participated in a repeated measurement design before (BMI, 30.3 ± 2.8 kg/m²; waist circumference, 92.6 ± 7.8 cm; hip circumference, 111.1 ± 7.4 cm) and after a weight loss period of 6 weeks (BMI, 28.2 ± 2.7 kg/m²; waist circumference, 85.5 ± 8.5 cm; hip circumference, 102.1 ± 9.2 cm). During weight loss, subjects received a very‐low‐calorie diet (Optifast) to replace three meals per day. Subjects came to the laboratory fasted, and after a baseline blood sample, received a standard breakfast (1.9 MJ). Postprandially, blood samples were taken every one‐half hour relative to intake for 120 minutes to determine GLP‐1, insulin, glucose, and free fatty acids from plasma. Appetite ratings were obtained with visual analog scales. Results: After weight loss, postprandial GLP‐1 concentrations at 30 and 60 minutes were significantly lower than before weight loss (p < 0.05). Glucose concentrations were also lower, and free fatty acids were higher compared with before weight loss. Ratings of satiety were increased, and hunger scores were decreased after weight loss (p < 0.05). Discussion: In overweight/obese subjects, GLP‐1 concentrations after weight loss were decreased compared with before weight loss, and nutrient‐related stimulation was abolished. This might be a response to a proceeding negative energy balance. Satiety and GLP‐1 seem to be unrelated in the long term.     

The effect of tesofensine on appetite sensations

Tesofensine (TE), an inhibitor of monoamine presynaptic reuptake, has produced twice the weight loss seen with currently marketed drugs. However, its long term effect on appetite in humans has not been studied. A multicentre phase II trial was divided into two parts (24 weeks each). Part 1 had a randomized, double‐blind, placebo‐controlled design and Part 2, an open‐labeled, single‐group, uncontrolled design. A drug‐free period (12 ± 3 weeks) separated them. In Part 1, participants (n = 158) were assigned to 0.25, 0.5 or 1.0 mg TE, or placebo. Completers of Part 1 were invited to participate in Part 2 (n = 113), during which they all received 0.5 or 1.0 mg TE. Appetite sensations and a composite satiety score (CSS = satiety + fullness + (100 − hunger) + (100 − prospective food consumption) were assessed. In Part 1 TE induced a dose‐dependent increase in CSS at week 12 that correlated with weight loss during the 24 weeks (r = 0.36, P < 0.0001). However, CSS diminished over time as weight loss progressed (e.g., for 1.0 mg; 52 ± 17 mm; 64 ± 13 mm; 55 ± 13 mm at baseline, week 12 and week 24, respectively). After drug withdrawal CSS returned to baseline values (50 ± 17 mm, in the whole sample.), despite the participants' reduced‐weight state (−7.2 ± 6.7 kg, P < 0.0001). The reintroduction of TE in Part 2 increased CSS again (56 ± 17 mm at week 60), regardless of initial treatment/weight loss. We postulate that enhanced satiety is involved in early weight loss. Whether the attenuated effect on appetite seen after 24 weeks is due to a counteracting effect in the weight reduced state or whether the appetite suppressing effect of TE per se diminishes over time is, however, still unclear.     

Enhanced Weight Loss Following Coadministration of Pramlintide With Sibutramine or Phentermine in a Multicenter Trial

Preclinical evidence suggests that pharmacotherapy for obesity using combinations of agents targeted at distinct regulatory pathways may produce robust additive or synergistic effects on weight loss. This randomized placebo‐controlled trial examined the safety and efficacy of the amylin analogue pramlintide alone or in combination with either phentermine or sibutramine. All patients also received lifestyle intervention. Following a 1‐week placebo lead‐in, 244 obese or overweight, nondiabetic subjects (88% female; 41 ± 11 years; BMI 37.7 ± 5.4 kg/m²; weight 103 ± 19 kg; mean ± s.d.) received placebo subcutaneously (sc) t.i.d., pramlintide sc (120 µg t.i.d.), pramlintide sc (120 µg t.i.d.) + oral sibutramine (10 mg q.a.m.), or pramlintide sc (120 µg t.i.d.) + oral phentermine (37.5 mg q.a.m.) for 24 weeks. Treatment was single‐blind for subjects receiving subcutaneous medication only and open‐label for subjects in the combination arms. Weight loss achieved at week 24 with either combination treatment was greater than with pramlintide alone or placebo (P < 0.001; 11.1 ± 1.1% with pramlintide + sibutramine, 11.3 ± 0.9% with pramlintide + phentermine, ?3.7 ± 0.7% with pramlintide; ?2.2 ± 0.7% with placebo; mean ± s.e.). Elevations from baseline in heart rate and diastolic blood pressure were demonstrated with both pramlintide + sibutramine (3.1 ± 1.2 beats/min, P < 0.05; 2.7 ± 0.9 mm Hg, P < 0.01) and pramlintide + phentermine (4.5 ± 1.3 beats/min, P < 0.01; 3.5 ± 1.2 mm Hg, P < 0.001) using 24‐h ambulatory monitoring. However, the majority of subjects receiving these treatments remained within normal blood pressure ranges. These results support the potential of pramlintide‐containing combination treatments for obesity.     

Effects of Sibutramine Plus Orlistat in Obese Women Following 1 Year of Treatment by Sibutramine Alone: A Placebo‐Controlled Trial

Objective: This study assessed whether adding orlistat to sibutramine would induce further weight loss in patients who previously had lost weight while taking sibutramine alone. Research Methods and Procedures: Patients were 34 women with a mean age of 44.1 ± 10.4 years, weight of 89.4 ± 13.8 kg, and body mass index (BMI) of 33.9 ± 4.9 kg/m² who had lost an average of 11.6 ± 9.2% of initial weight during the prior 1 year of treatment by sibutramine combined with lifestyle modification. Patients were randomly assigned, in double‐blind fashion, to sibutramine plus orlistat or sibutramine plus placebo. In addition to medication, participants were provided five brief lifestyle modification visits during the 16‐week continuation trial. Results: Mean body weight did not change significantly in either treatment condition during the 16 weeks. The addition of orlistat to sibutramine did not induce further weight loss as compared with treatment by sibutramine alone (mean changes = +0.1 ± 4.1 kg vs. +0.5 ± 2.1 kg, respectively). Discussion: These results must be interpreted with caution because of the study's small sample size. The findings, however, suggest that the combination of sibutramine and orlistat is unlikely to have additive effects that will yield mean losses ≥15% of initial weight, as desired by many obese individuals.     

Weight loss on the web: A pilot study comparing a structured behavioral intervention to a commercial program

Objective: Internet weight loss programs have become widely available as alternatives to standard treatment, but few data are available on their efficacy. This study aimed to investigate the effectiveness of a structured behavioral weight loss website (VTrim) vs. a commercial weight loss website ( eDiets.com ). Research Methods and Procedures: A randomized, controlled trial was conducted from February 2003 to March 2005, in 124 overweight and obese subjects ages 18 years and older with a BMI of 25 to 39.9 kg/m² (mean age, 47 ± 9 years; BMI, 32 ± 3 kg/m²; 20% men). Analyses were performed for the 88 subjects who had complete follow‐up data. Participants were randomly assigned to 12‐month VTrim (n = 62) or eDiets.com (n = 62) intervention. VTrim participants had access to a therapist‐led structured behavioral weight loss program delivered on‐line. eDiets.com subjects had access to a self‐help commercial on‐line weight loss program. Body weight, social support, and use of website components were measured at 0, 6, and 12 months. Results: Repeated‐measures analyses showed that the VTrim group lost significantly more weight than the eDiets.com group at 6 months (8.3 ± 7.9 kg vs. 4.1 ± 6.2 kg; p = 0.004) and maintained a greater loss at 12 months (7.8 ± 7.5 kg vs. 3.4 ± 5.8 kg; p = 0.002). More participants in the VTrim group maintained a 5% weight loss goal (65% vs. 37.5%; p = 0.01) at 12 months. Discussion: An on‐line, therapist‐led structured behavioral weight loss website produced greater weight loss than a self‐help commercial website. Because commercial sites have great potential public health impact, future research should investigate the feasibility of incorporating a more structured behavioral program into a commercial application.     

Observational study of bone accretion during successful weight loss in obese adolescents

Objective: To assess bone mineral content (BMC) among obese adolescents who lose weight during a critical period for bone accretion. Methods and Procedures: Whole body, lumbar spine, lower, and upper limb BMC were measured in 62 obese adolescents who completed an intensive 12‐month weight loss trial. BMC was adjusted for height (z ‐scores) using data from a reference group of 66 adolescents (who were 18% overweight). Results: At baseline, the BMC of the obese group was higher than the reference group. During the 12‐month weight loss program, unadjusted BMC increased among the obese adolescents, despite successful weight loss. After adjustment for height, whole body BMC did not change significantly from baseline to 12 months (mean ± s.d.: 1.08 ± 0.67 to 1.06 ± 0.67, P = 0.7). Region‐specific BMC‐for‐height however decreased for the lower (1.07 ± 0.57 to 0.95 ± 0.59, P < 0.001) and upper (1.29 ± 0.56 to 1.18 ± 0.57, P = 0.01) limbs, but lumbar spine BMC‐for‐height increased (0.14 ± 1.06 to 0.40 ± 0.94, P < 0.001). These changes were largely and independently explained by changes in lean and fat mass. Discussion: This study confirms that obese adolescents have high BMC for height and suggests that, unlike adults, their BMC continues to increase during weight loss and remains higher than the BMC of a reference group. After adjustment for growth‐related changes, lower and upper limb BMC appears to decrease, while lumbar spine BMC appears to increase. These results suggest that to optimize the health benefits of weight loss among obese adolescents, their bone health should be better understood and addressed.     

Endothelial function and weight loss: Comparison of low‐carbohydrate and low‐fat diets

Objective: The effect of weight loss on obesity‐associated endothelial dysfunction is not clear because of conflicting data, demonstrating both improvement and no change in endothelial function after weight loss in obese subjects. A 2‐year prospective study (n = 121) was conducted to examine: (1) the effect of obesity and weight loss (either a low‐carbohydrate or and low‐fat diet) on flow mediated vasodilatation (FMD), a measure of endothelial function. Design and Methods: Participants reduced body weight by 7.1% ± 4.4%, 8.7% ± 6.8%, 7.1% ± 7.8%, and 4.1% ± 7.7% at 3, 6, 12, and 24 months, respectively with no significant differences between the low‐fat and low‐carbohydrate groups. Results: Endothelial function was inversely correlated with waist circumference, triglyceride level, and directly correlated with leptin in obese persons prior to weight loss. These weight losses did not confer any improvements in FMD. There were no differences between the low‐fat and low‐carbohydrate diets in FMD at any time point. At 6 months (r = 0.26, P = 0.04) and 1 year (r =0.28, P = 0.03), there were positive correlations between change in FMD and change in leptin but not at 2 years. Conclusion: There was no significant improvement in endothelial function after 7.1% ± 7.8% weight loss at 1 year and 4.1% ± 7.7% at 2 years, achieved by either a low carbohydrate or a low fat diet.