Effect of cimetidine suspension on appetite and weight in overweight subjects.

OBJECTIVE--To investigate the weight reducing effect of cimetidine, comparing it with placebo. DESIGN--Block randomised parallel group double blind study using suspensions with identical appearance and taste. SETTING--Primary care practice. SUBJECTS--55 women and 5 men aged 18-59, body mass index 25-37 kg/m2, completed the study according to the protocol. INTERVENTIONS--Cimetidine suspension 200 mg or placebo 30 minutes was given before the three main meals for eight weeks. Subjects followed a diet restricted to 5 MJ/day supplemented with 9 g fibre per day. MAIN OUTCOME MEASURES--Weight reduction; abdominal and hip circumferences and systolic and diastolic blood pressures were also recorded. RESULTS--Subjects given cimetidine lost a mean of 7.3 (95% confidence interval 6.5 to 8.3) kg more than subjects given placebo (p < 0.001); body mass index decreased 3.33 (SD 0.76) and 0.77 (0.43), respectively (p < 0.001). Abdominal and hip circumference was decreased more in the cimetidine group (8.6 (3.9) cm and 7.8 (3.1) cm) than in the placebo group (2.2 (1.5) cm and 2.1 (1.5) cm). Mean reductions in systolic and diastolic blood pressure were greater in the cimetidine group than the placebo group (mean 5.8 v 0.4 and 6.5 v 0.4, p < 0.001). CONCLUSION--Intake of cimetidine suspension 30 minutes before meals in overweight subjects may lead to reduced hunger, less food intake, and subsequent weight loss. This effect may be due to the suppression of gastric acid secretion. Cimetidine suspension may be a valuable adjunct in treating obesity.     

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.     

A Randomized Double-Blind Crossover Study of the Antiobesity Effects of Etiocholanedione

Etiocholanedione (ED), a natural metabolite of dehy-droepiandrosterone, has antiobesity effects in animals when given orally and is nontoxic. We carried out a trial of oral ED in obese humans. In a 20-week randomized double-blind crossover study, 14 subjects lost significantly more weight and body fat during treatment with oral ED, 4 gm daily, than during placebo administration. Mean weight loss during ED administration was 2.8 ± 5.5 kilograms, which was equivalent to 0.53 k 0.91 kilograms per week per 100 kilograms of body fat; mean weight change during placebo administration was essentially zero: M.21 ± 4.2 kg, or 4.04 ± 0.74 kg/wk/100 kg body fat. The difference between the weight changes in the two periods was significant: for A kg, P<0.05; for Δ kg/wk/100 kg body fat, P<0.03. Densitometric measurement of body fat content showed that the mean weight loss coincided almost exactly with the mean decrease in fat content; thus, over the 10-week period of ED administration, the mean fat loss was about 5% of the initial body fat content. Three of the obese subjects had strikingly greater fat loss, about 18%, 19%, and 25% of the initial body fat content. There were no significant subjective or objective side effects of ED administration .     

Usefulness of Fluoxetine in Obese Non-Insulin-Dependent Diabetics: A Multicenter Study

Weight reduction is essential in the management of most noninsulin-dependent diabetics, but this therapeutical goal is difficult to obtain. In this double-blind parallel study, 82 noninsulin-dependent diabetics, moderately obese (BMI = 30–39 kg/nr²), were given for an 8-week period either placebo (P) or fluoxetine (F), a specific serotonin reuptake inhibitor, in addition to their usual antidiabetic treatment. Thirty-nine of them received 60 mg fluoxetine a day and 43 were given the placebo. At admission, both groups had similar weight excess, metabolic control and serum lipid values. In comparison with the P-treated subjects, those treated with fluoxetine (F) lost more weight after 3 weeks (-1.9 vs. ?0.7 kg, p<0.0009) and after 8 weeks (-3.1 vs. ?0.9 kg, p<0.0007). Fasting blood glucose decreased in group F after 3 weeks (- 1.5 vs. ?0.4 mmol/L, p<0.003) and after 8 weeks (-1.7 vs. ?0.02 mmol/L, p<0.0004). HbAlc decreased from 8.5% to 7.7% in group F and from 8.6% to 8.3% in group P (p=0.057). Mean triglyceride level was also reduced in group F after 8 weeks (p=0.042). Fasting C-pep-tide did not change in either group, but fasting insulin values decreased in group F after 3 weeks (p<0.02) and after 8 weeks (p<0.05). The insulin/C-peptide molar ratio decreased significantly in group F after 3 weeks (p<0.04) and after 8 weeks (p<0.05) in comparison with group P. The drug was generally well tolerated and no major side effects were reported. In conclusion, the addition of fluoxetine to the usual oral hypoglycemic agent therapy might be beneficial in obese non-insulin-dependent diabetics, at least on a short-term basis.     

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.     

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.     

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.     

Six‐Month Treatment of Obesity with Sibutramine 15 mg; A Double‐Blind,Placebo‐Controlled Monocenter Clinical Trial in a Hispanic Population

Objective: To evaluate the safety and efficacy of sibutramine 15 mg by mouth once per day in obese patients over a period of 6 months. Research Methods and Procedures: A monocenter, double‐blind, placebo controlled, parallel, prospective clinical trial was carried out. Sixty‐nine male and female obese patients (body mass index [BMI] > 30 kg/m²) aged 16 to 65 years entered the trial. Results: 22 of 35 patients in the sibutramine group and 9 of 34 patients in the placebo group completed the trial. The high dropout rate in the sibutramine group was due to adverse events in 3 cases, lack of efficacy (as judged by patients) in 7, loss to follow‐up in 2, and an orthopedic device being worn in 1; in the placebo group the dropouts were ascribed to lack of efficacy (as judged by patients) in 17 cases and to loss to follow‐up in 8 cases. Using the method of last observation carried forward, the weight loss in the sibutramine group was 10.27 kg (95% confidence intervals [95% CI] 7.66; 13.07) and 1.26 kg (95% CI 0.3; 2.23) in the placebo group. The BMI loss was 4.17 kg/m² (95% CI 3.11; 5.22) in the sibutramine group and 0.53 kg/m² (95% CI 0.13; 0.92) in the placebo group. The waist circumference reduction was 12.51 cm (95% CI 9.25; 15.77) in the sibutramine group and 3.26 cm (95% CI 1.38; 5.14) in the control group (p < 0.05 by paired Student's t test for all the intragroup comparisons). Twenty‐three sibutramine patients had 34 adverse events, the most frequent adverse events in the sibutramine group were upper respiratory tract infections (n = 6) and constipation (n = 6); 16 placebo patients had 21 adverse events. Three sibutramine patients withdrew their informed consent when they had adverse events. Discussion: The results show that sibutramine induces significant loss of body weight and waist circumference. Cardiovascular function was not significantly affected by sibutramine. Sibutramine was well tolerated by most of the patients.     

Is DL-Fenfluramine a Potentially Helpful Drug Therapy in Overweight Adolescent Subjects?

We have studied the therapeutic effects of two different doses (30 mg and 60 mg, twice daily) of DL-fen-fluramine (DL-F) in, respectively, prepuberal (11–13 years old) and adolescent subjects (14–17 years old). Sixty-eight obese subjects were recruited for this study (22 boys, 36 girls, aged 10–17 years old) with body mass index ranging from 24.5 to 44.0 kg/m², absolute weight ranging from 37.0 to 119.5 kg and % over IBW ranging from 122% to 260%. Results were compared to a placebo treated group of obese adolescent patients (n=17), 6 boys and 11 girls, aged 10–17 years old, BMI ranging from 26–44 kg/m², absolute weight 53.1 to 96.5 kg, and with 129% to 253% over IBW. In the DL-F-treated subjects most patients (n=41) had a continuous weight loss during 12 months but 27 individuals were unable to lose any additional weight after the initial 6 months of the trial. Taken together 65% of all patients lost weight during DL-F treatment (12 months) whereas only 17.4% of the placebo group lost a significant (>10% BMI) amount of excess weight. Also the placebo group had a higher withdrawal rate (57%) as compared with the DL-F-treated group (24%). There was a significant (p<0.05) decrease of the mean & SD of the BMI (at 6 and 12 months of therapy). No significant change of the BMI was observed for control group. Minor adverse side effects consisted of a brief period of drowsiness and dry mouth. Our findings indicated that the continuous administration of DL-Fenfluramine might help obese adolescent subjects adhere to a diet and to maintain the weight loss achieved without major or harmful adverse effects .     

Lorcaserin (APD356), a Selective 5‐HT2C Agonist,Reduces Body Weight in Obese Men and Women

Lorcaserin (APD356) is a potent, selective 5‐HT_2C agonist with ∼15‐fold and 100‐fold selectivity vs. 5‐HT_2A and 5‐HT_2B receptors, respectively. This study evaluated the safety and efficacy of lorcaserin for weight reduction in obese patients during a 12‐week period. The randomized, double‐blind, placebo‐controlled, parallel‐arm study enrolled 469 men and women between ages 18 and 65 and with BMI 30–45 kg/m². Patients received placebo, lorcaserin 10 mg q.d., lorcaserin 15 mg q.d., or lorcaserin 10 mg b.i.d. for 12 weeks, and were counseled to maintain their usual diet and activity. The primary end point was change in weight from baseline to day 85 by completer analysis. Safety analyses included echocardiograms at Screening and day 85/study exit. Lorcaserin was associated with progressive weight loss of 1.8 kg, 2.6 kg, and 3.6 kg at 10 mg q.d., 15 mg q.d., and 10 mg b.i.d., respectively, compared to placebo weight loss of 0.3 kg (P < 0.001 for each group). Similar results were seen by intent‐to‐treat last observation‐carried forward (ITT‐LOCF) analysis. The proportions of completers achieving ≥5% of initial body weight were 12.8, 19.5, 31.2, and 2.3% in the 10 mg q.d., 15 mg q.d., 10 mg b.i.d., and placebo groups, respectively. The most frequent adverse events (AEs) were transient headache, nausea, and dizziness. Echocardiograms showed no apparent drug‐related effects on heart valves or pulmonary artery pressure (PAP). Lorcaserin was well tolerated and efficacious for weight reduction in this 12‐week study. Longer‐term trials employing behavior modification will be needed to more fully assess its safety and efficacy.     

Weight Loss,HbA1c Reduction,and Tolerability of Cetilistat in a Randomized,Placebo‐controlled Phase 2 Trial in Obese Diabetics: Comparison With Orlistat (Xenical)

The objective of this multicenter, randomized, double‐blind study was to determine the efficacy and safety of cetilistat and orlistat relative to placebo in obese patients with type 2 diabetes, on metformin. Following a 2‐week run‐in, patients were randomized to placebo, cetilistat (40, 80, or 120 mg three times daily), or orlistat 120 mg t.i.d., for 12 weeks. The primary endpoint was absolute change in body weight from baseline. Secondary endpoints included other measures of obesity and glycemic control. Similar reductions in body weight were observed in patients receiving cetilistat 80 or 120 mg t.i.d. or 120 mg t.i.d. orlistat; these reductions were significant vs. placebo (3.85 kg, P = 0.01; 4.32 kg, P = 0.0002; 3.78 kg, P = 0.008). In the 40 mg t.i.d. and placebo groups, reductions were 2.94 kg, P = 0.958 and 2.86 kg, respectively. Statistically significant reductions in glycosylated hemoglobin (HbA_1c) were noted. Cetilistat was well tolerated, and showed fewer discontinuations due to adverse events (AEs) than in the placebo and orlistat groups. Discontinuation in the orlistat group was significantly worse than in the 120 mg cetilistat and placebo groups and was entirely due to gastrointestinal (GI) AEs. Treatment with cetilistat 80 or 120 mg t.i.d., or with orlistat 120 mg t.i.d., significantly reduced body weight and improved glycemic control relative to placebo in obese diabetic patients. Cetilistat was well tolerated with the number of discontinuations due to AEs being similar to placebo.     

Effect of Orlistat in Obese Patients with Binge Eating Disorder

Objective: Binge eating disorder represents a significant public health problem, with up to 50% of weight loss program participants displaying this disorder. In previous studies with orlistat, patients with binge eating disorder were excluded. The goal of this study was to assess the efficacy of orlistat in obese patients with binge eating disorder. Research Methods and Procedures: Eighty‐nine patients with clinically diagnosed binge eating disorder and a BMI ≥ 30 kg/m² were randomized in double‐blind fashion to 24 weeks of treatment with 120 mg of orlistat or placebo three times daily, in combination with a mildly reduced‐calorie diet. Results: After 24 weeks, the mean weight loss from baseline for orlistat‐treated patients was significantly greater than for patients receiving placebo (?7.4% vs. ?2.3%; p = 0.0001) (intent‐to‐treat analysis). The overall Eating Disorder Inventory 2 score at week 24 was significantly lower in patients treated with orlistat than in those in the placebo group (p = 0.011) Discussion: Orlistat may be considered as part of the management for patients with obesity and binge eating disorder.     

Bupropion for Weight Loss: An Investigation of Efficacy and Tolerability in Overweight and Obese Women

Objective: On the basis of the clinical observations that bupropion facilitated weight loss, we investigated the efficacy and tolerability of this drug in overweight and obese adult women. Research Methods and Procedures: A total of 50 overweight and obese (body mass index: 28.0 to 52.6 kg/m²) women were included. The core component of the study was a randomized, double‐blind, placebo‐controlled comparison for 8 weeks. Bupropion or placebo was started at 100 mg/d with gradual dose increase to a maximum of 200 mg twice daily. All subjects were prescribed a 1600 kcal/d balanced diet and compliance was monitored with food diaries. Responders continued the same treatment in a double‐blind manner for an additional 16 weeks to a total of 24 weeks. There was additional single‐blind follow‐up treatment for a total of 2 years. Results: Subjects receiving bupropion achieved greater mean weight loss (last‐observation‐carried‐forward analysis) over the first 8 weeks of the study (p = 0.0001): 4.9% ± 3.4% (n = 25) for bupropion treatment compared with 1.3% ± 2.4% (n = 25) for placebo treatment. For those who completed the 8 weeks, the comparison was 6.2% ± 3.1% (n = 18) vs. 1.6% ± 2.9% (n = 13), respectively(p = 0.0002), with 12 of 18 of the bupropion subjects (67%) losing over 5% of baseline body weight compared with 2 of 13 in the placebo group (15%; p = 0.0094). In the continuation phase, 14 bupropion responders who completed 24 weeks achieved weight loss of 12.9% ± 5.6% with fat accounting for 73.5% ± 3.7% of the weight lost and no change in bone mineral density as assessed by DXA. Bupropion was generally well‐tolerated in this sample. Discussion: Bupropion was more effective than placebo in achieving weight loss at 8 weeks in overweight and obese adult women in this preliminary study. Initial responders to bupropion benefited further in the continuation phase.     

The Addition of Dexfenfluramine to Fluoxetine in the Treatment of Obesity: A Randomized Clinical Trial

Current evidence demonstrates that pharmacologic agents, alone or in combination produce short-term weight-loss and may remain effective for extended periods of time in obese patients. We have evaluated the weight loss of a selective inhibitor of serotonin uptake, fluoxetine, alone as compared with combined therapeutic trial with another serotoninergic drug, dexfenfluramine. Thirty-three patients were randomly assigned in a double-blind randomized clinical trial divided to two groups: Group I [Fluoxetine 40 mg and placebo (n=13)] and Group II [Fluoxetine 40 mg plus dexfenfluramine 15 mg at night (n=20)]. Both groups had a significant weight loss at the end of 8 months (Group I, mean ± SEM 6.2 ± 2.8 kg and Group II 13.4 ± 6.3 kg, p < 0.05). Group II patients had a significantly greater weight loss as compared with Group I both in terms of mean weight loss in kg and BMI in kg/m². However significance between Group I and II related to BMI mean values and weight mean values were only achieved after, respectively, 4 and 6 months of treatment. At laboratory level there was an elevation of HDL-cholesterol and lowering of serum lipids values (cholesterol and triglycerides) in both groups. Side effects were relatively minor and no altered clinical vital signs or abnormal laboratory values were observed. We concluded that the combination of fluoxetine (daytime) and dexfenfluramine (at night) may be more effective than fluoxetine alone in weight reduction although the small size of this study does not permit broad generalization.     

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.

     

Low-dose growth hormone treatment with diet restriction accelerates body fat loss, exerts anabolic effect and improves growth hormone secretory dysfunction in obese adults.

Growth hormone (GH) can induce an accelerated lipolysis. Impaired secretion of GH in obesity results in the consequent loss of the lipolytic effect of GH. Dietary restriction as a basic treatment for obesity is complicated by poor compliance, protein catabolism, and slow rates or weight loss. GH has an anabolic effect by increasing insulin-like growth factor (IGF)-I. We investigated the effects of GH treatment and dietary restriction on lipolytic and anabolic actions, as well as the consequent changes in insulin and GH secretion in obesity. 24 obese subjects (22 women and 2 men; 22-46 years old) were fed a diet of 25 kcal/kg ideal body weight (IBW) with 1.2 g protein/kg IBW daily and were treated with recombinant human GH (n = 12, 0.18 U/kg IBW/week) or placebo (n = 12, vehicle injection) in a 12-week randomized, double-blind and placebo-controlled trial. GH treatment caused a 1.6-fold increase in the fraction of body weight lost as fat and a greater loss of visceral fat area than placebo treatment (35.3 vs. 28.5%, p < 0.05). In the placebo group, there was a loss in lean body mass (-2.62 +/- 1.51 kg) and a negative nitrogen balance (-4.52 +/- 3.51 g/day). By contrast, the GH group increased in lean body mass (1.13 +/- 1.04 kg) and had a positive nitrogen balance (1.81 +/- 2.06 g/day). GH injections caused a 1.6-fold increase in IGF-I, despite caloric restriction. GH response to L-dopa stimulation was blunted in all subjects and it was increased after treatment in both groups. GH treatment did not induce a further increase in insulin levels during an oral glucose tolerance test (OGTT) but significantly decreased free fatty acid (FFA) levels during OGTT. The decrease in FFA area under the curve during OGTT was positively correlated with visceral fat loss. This study demonstrates that in obese subjects given a hypocaloric diet, GH accelerates body fat loss, exerts anabolic effects and improves GH secretion. These findings suggest a possible therapeutic role of low-dose GH with caloric restriction for obesity.     

Ghrelin as a potential blood pressure reducing factor in obese women during weight loss treatment

BACKGROUND: In animal models ghrelin reduces cardiac afterload and increases cardiac output via receptors in the cardiovascular system. The aim of our study was to evaluate a potential relationship between weight loss treatment, blood pressure and serum ghrelin concentrations in obese women. MATERIAL AND METHODS: A group of 37 obese premenopausal women with no previous history of hypertension (BMI: 36.5 +/- 5 kg/m2) were involved in the study. Blood pressure and serum ghrelin levels were assessed before and after a three-month weight reduction treatment, which consisted of a diet of 1000 kcal/day and physical exercise. Body composition was determined by impedance analysis using Bodystat. RESULTS: Following weight loss (mean 8.9 +/- 4.8 kg) SBP decreased (120 +/- 13 vs. 115 +/- 14 mm Hg, p = 0.01) and serum ghrelin levels increased significantly (66.9 +/- 13.7 vs. 73.9 +/- 15.4 pg/ml; p = 0.005). There were significant correlations between values for ghrelin levels after weight loss and SBP (r = -0.45, p = 0.02), DBP (r = -0.41, p < 0.05), and between Deltaghrelin levels and DeltaSBP (r = 0.52, p = 0.006), DeltaDBP (r = 0.53, p = 0.005). There was a positive correlation between an increase in ghrelin and a decrease in percentage body fat during weight loss (r = 0.51; p = 0.002). CONCLUSION: The results seem to provide evidence that weight loss may decrease blood pressure in obese patients via a ghrelin-dependent mechanism.     

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.     

The Effect of Glucagon-Like Peptide 1 Receptor Agonists on Weight Loss in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison Meta-Analysis

Aims

To determine the effects of glucagon-like peptide-1 receptor agonists compared with placebo and other anti-diabetic agents on weight loss in overweight or obese patients with type 2 diabetes mellitus.

Methods

Electronic searches were conducted for randomised controlled trials that compared a glucagon-like peptide-1 receptor agonist therapy at a clinically relevant dose with a comparator treatment (other type 2 diabetes treatment or placebo) in adults with type 2 diabetes and a mean body mass index ≥ 25kg/m². Pair-wise meta-analyses and mixed treatment comparisons were conducted to examine the difference in weight change at six months between the glucagon-like peptide-1 receptor agonists and each comparator.

Results

In the mixed treatment comparison (27 trials), the glucagon-like peptide-1 receptor agonists were the most successful in terms of weight loss; exenatide 2mg/week: -1.62kg (95% CrI: -2.95kg, -0.30kg), exenatide 20μg: -1.37kg (95% CI: -222kg, -0.52kg), liraglutide 1.2mg: -1.01kg (95%CrI: -2.41kg, 0.38kg) and liraglutide 1.8mg: -1.51 kg (95% CI: -2.67kg, -0.37kg) compared with placebo. There were no differences between the GLP-1 receptor agonists in terms of weight loss.

Conclusions

This review provides evidence that glucagon-like peptide-1 receptor agonist therapies are associated with weight loss in overweight or obese patients with type 2 diabetes with no difference in weight loss seen between the different types of GLP-1 receptor agonists assessed.     

Lipase Inhibition and Hormonal Status,Body Composition and Gastrointestinal Processing of a Liquid High-Fat Mixed Meal in Moderately Obese Subjects

DRENT, MADELEINE L, CORRIE POPP-SNIJDERS, HERMAN J ADER, JAN BMJ JANSEN AND EDUARD A VAN DER VEEN. Lipase inhibition and hormonal status, body composition and gastrointestinal processing of a liquid high-fat mixed meal in moderately obese subjects. Obes Res. The effect of Orlistat, a lipase inhibitor used in the treatment of obesity was studied on gastrointestinal transit time, on body composition and on hormones known to be influenced by the degree of hydrolysis of nutritional triglycerides or by reduced nutrient intake and absorption. After a placebo run-in period 14 patients were randomized to a 12-week treatment period on Orlistat 360 mg per day (mean body weight 93.1 ± 9.8 kg) or placebo (mean body weight 90.7 ± 10.5 kg). At randomization and after 12 weeks body weight, body composition, thyroid hormones, catecholamines, insulin-like growth factor I (IGF-I) and IGF-binding protein 3 were measured. During 4 hours after consumption of a liquid fat-rich mixed meal containing study medication, 15 g lactulose and 25 g xylose, blood levels of glucose, insulin, c-peptide, glucagon, triglycerides, free fatty acids, cholecys-tokinin, pancreatic polypeptide and xylose and expiration air levels of hydrogen were measured. Weight loss was 4.2 ± 3.5 kg in the Orlistat group versus 3.0 ± 1.9 kg in the placebo group. Fat mass decreased to an equal degree, whereas lean body mass remained stable. No differences were found for thyroid hormones, catecholamines, IGF-I and IGFBP-3 levels. By comparing the areas under the curve (AUC) and the peak levels at randomization (acute effects) of insulin and c-peptide a tendency was found to be increased in the Orlistat group, whereas those of xylose were increased significantly, suggesting faster gastric empyting after Orlistat. No differences were found in the other parameters. By comparing the changes in responses (longer term effects) no significant differences were found. In conclusion, the presence in the gut of undigested and unabsorbed fat does not seem to have a relevant influence on hormonal status and body composition in a small group of moderately obese patients.