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PubMed2025

Oral semaglutide for weight loss and liver fibrosis in overweight and obesity: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: Obesity is a leading risk factor for fatty liver disease and weight loss has been shown to improve liver parameters. This study evaluates the efficacy of oral semaglutide for weight loss in individuals with overweight or obesity, excluding those with diabetes mellitus. METHODS: A randomized, open-label, controlled trial was conducted at the Asian Institute of Gastroenterology, Hyderabad, from June 2022 to December 2023. Adults (≥ 18 years) with a body mass index (BMI) ≥ 30 or ≥ 27 with comorbidities (pre-diabetes, hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease) were randomized into two groups. Both groups received counselling on a reduced-calorie diet and increased physical activity. Group 1 also received oral semaglutide, starting at 3 mg/day and titrated to 14 mg/day over two to four weeks. The objectives were to assess the effects of semaglutide on weight loss, non-invasive markers of liver fibrosis and cardiometabolic parameters. (ClinicalTrials.gov ID: NCT05442450). RESULTS: Total 116 participants (58 per group) completed the study. At 28 weeks, the mean percentage weight reduction was -10.47% (SD 5.3) in the Semaglutide group vs. -2.4% (SD 4.5) in the control group (p < 0.001). Semaglutide treatment significantly improved alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) levels, along with reductions in the aspartate aminotransferase to platelet ratio index (APRI) score, liver fat content and liver stiffness. However, NFS (NAFLD fibrosis score) and FIB-4 (fibrosis-4 index) did not show significant reductions. Improvements in BMI, waist circumference, HbA1c, fasting insulin and C-reactive protein (CRP) were significantly greater with semaglutide (p < 0.001). Total fat mass decreased by 7.3 kg vs. 1.74 kg (p < 0.0001) in controls, while visceral fat ratings dropped by 3.67 vs. 0.6 (p < 0.0001). CONCLUSIONS: In adults with overweight or obesity without diabetes, oral semaglutide, combined with dietary and lifestyle modifications, led to significant and clinically meaningful weight loss and metabolic improvements compared to lifestyle modifications alone.

Adult↗

PubMed2026

Comparative Efficacy of Tirzepatide Versus Semaglutide for Weight Loss in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis of Head-to-Head Studies.

This systematic review and meta-analysis aimed to compare the efficacy and safety of tirzepatide versus semaglutide for weight reduction in adults with overweight or obesity. We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up. The primary outcome was percentage weight change from baseline. Secondary outcomes included absolute weight change, weight-loss thresholds, HbA1c and safety outcomes. Ten studies including 41 381 participants were analysed. Tirzepatide was associated with greater percentage weight reduction than semaglutide (MD -4.28 percentage points; 95% CI -5.28 to -3.28; p < 0.00001) and greater absolute weight loss (MD -4.43 kg; 95% CI -5.56 to -3.30; p < 0.00001). Tirzepatide was also associated with a higher likelihood of achieving ≥ 10%, ≥ 15% and ≥ 20% weight loss, with no difference at ≥ 5%. HbA1c reduction was greater with tirzepatide (MD -0.29%; p = 0.0002). Subgroup analyses by study design and type 2 diabetes status yielded consistent findings. There was no significant difference in treatment discontinuation due to adverse events (RR 1.28; p = 0.54), whereas serious adverse events were more frequent with tirzepatide (RR 1.83; p = 0.007). Overall and gastrointestinal adverse events were similar between groups. Tirzepatide was associated with greater weight reduction, greater glycaemic benefit and a higher likelihood of achieving weight-loss thresholds than semaglutide, but with a higher risk of serious adverse events.

Humans↗

PubMed1977

Anticipated rate of weight loss during dieting.

Two hundred and thirty-five females anxious to lose weight were asked to state their anticipated rate of weight loss each week or each month after the first few weeks of dieting. They were divided into four groups of 50 subjects, one group enrolling in a slimming club for the first time, one group already attending the same slimming organisation and two groups on first attendance at one of two hospital obesity clinics. The remaining group comprised 35 subjects re-enrolling in a slimming club. Only 27 per cent of those interviewed on their first attendance had a realistic concept of the anticipated rate of weight loss (AROWL) while 60 per cent of those re-enrolling and 90 per cent of those currently attending a slimming club were realistic in their expectations. The younger subjects were significantly more obese and the least realistic concepts of the AROWL were held by those subjects most in excess of their ideal weight. This study highlights the frequency with which unrealistic concepts of the AROWL are held and suggests the need to reinforce realistic concepts of weight loss in the obese.

Adolescent↗

PubMed1979

Psychological impediments to weight loss.

An understanding of the possible psychologic impediments to weight loss can promote improved therapeutic intervention for the obese patient. Certain psychological tasks are imposed by chronic medical illness including obesity. The universal stresses that accompany medical illness, the basic threat to self-esteem and sense of intactness, the fear--of loss of love and approval, of loss of control of function, of injury to body parts, of pain, and of guilt--all become psychological impediments thwarting weight loss and its maintenance. The physician's awareness of these psychological stresses helps him identify areas of necessary support.

Anxiety, Separation↗

PubMed1975

Weight loss of prostatic tissue during electroresection.

During electroresection the weight loss of prostatic tissue was demonstrated to vary between 15 and 42% with a mean value of 26%. Using a scalpel the mean weight loss was 12%.

Electrosurgery↗

PubMed1977

Plasma fenfluramine levels, weight loss, and side effects.

Fifty women with refractory obesity received fenfluramine for 20 weeks. Every two weeks details of weight change, drug dose, degree of anorexia, and any side effects were recorded and plasma was obtained for fenfluramine and norfenfluramine measurements. Of the 41 patients available for final analysis 26 achieved a maximum plateau dose of 160 mg/day. Plasma fenfluramine concentrations did not correlate with the degree of anorexia or with the incidence of side effects other than the severity of dream disturbance. There was a highly significant relation between weight loss and plasma fenfluramine and norfenfluramine concentrations and also between weight loss and the presence of sustained anorexia. Women who achieved mean plateau concentrations over 200 ng/ml lost a mean 8.8 kg while those with concentrations less than 100 ng/ml lost a mean of only 2.1 kg. When fenfluramine is prescribed in refractory obesity the dose should be increased stepwise until either satisfactory weight loss is achieved or troublesome side effects appear.

Adult↗

PubMed1977

Factors responsible for weight loss in tropical sprue.

The respective roles of reduced dietary intake and malabsorption in the pathogenesis of weight loss in persons with chronic tropical sprue have been evaluated . Dietary intake was found to be significantly (P less than 0.001) less in a group of 45 patients with tropical sprue, all of whom had anorexia due to deficiency of folate and/or vitamin B12, than in a group of 51 healthy Puerto Ricans. Weight loss was equally prominent in those patients with tropical sprue who had normal absorption of fat and protein as in those who had excessive fecal loss and reduced absorption of these nutrients. Treatment of five sprue patients with folic acid or vitamin B12 for 2 weeks resulted in improved appetite and increased in dietary intake with weight gain in the absence of significant improvement in intestinal absorption. Treatment with oral tetracycline for a similar period of time in five other patients was not associated with vitamin repletion, return of appetite or weight gain. These observations indicate that reduced dietary intake resulting from anorexia caused by vitamin deficiency is a significant, and sometimes the most important, factor in the pathogenesis of weight loss in persons with chronic tropical sprue.

Anorexia↗

PubMed1979

Behavior modification in the treatment of obesity. The problem of maintaining weight loss.

The introduction of behavior modification in the treatment of obesity a decade ago resulted in a substantial increase in weight loss of persons treated for mild to moderate obesity. It has been hoped that this increased effectiveness of treatment would extend also to maintenance of weight loss, and the first controlled clinical trial suggested that it did. This article reports the results of (1) a five-year follow-up of this first trial and (2) all follow-up studies of behavior modification for obesity yet conducted, six published and four previously unpublished. A new method of data analysis shows that weight losses are only modestly maintained, although the question of how their maintenance compares with that of other treatments cannot be answered because comparable data on other treatments are not available. In contrast to the vast amount of work on the initiation and generalization of behavior change, study of its maintenance has been a neglected area of behavior modification. We suggest that this area constitutes a new frontier for research in behavior modification.

Behavior Therapy↗

PubMed1978

Factors determining weight loss in obese patients in a metabolic ward.

A metabolic unit is described in which it is possible to make controlled measurements of energy balance in patients with various types and degrees of obesity. Thirty-seven obese women were studied for three consecutive one-week periods on a diet which provided an average of 3.4MJ (800 kcal) daily, and some also undertook an exercise programme involving the expenditure of 850--1275 kJ (200--300 kcal) extra per day. The distribution of energy intake was varied from week to week, and within the day (nibbling and gorging), but neither these variations in dietary pattern nor the exercise programme significantly affected the total weight loss over the three-week study period. Very large variations were observed between individuals. Total weight loss over the three-week study period ranged from 1.6 to 9.8 kg. The best predictor of weight loss in a patient on a strictly controlled diet is the resting metabolic rate. The previous diet also affects weight loss: patients who had been keeping to a reducing diet before admission lost less weight, especially in the first week, than those who had not been dieting immediately before admission to hospital.

Body Height↗

PubMed1978

Role of caloric intake in the weight loss after jejunoileal bypass for obesity.

Sixty-five patients were studied prospectively after jejunoileal bypass for obesity. Dietary intake pre- and postoperatively was measured either directly by weighing food or by a research dietary history. Of 65 measurements, 59 were made at least 6 months after operation, when over 75% of weight loss had been achieved. Fat absorption was measured in 42 of the patients. The entire group ate fewer calories (mean +/- SE = 2595 +/- 135) postoperatively than preoperatively (mean +/- SE = 3261 +/- 138). This difference was highly significant (P less than 0.001). Forty-eight patients ate less after their operation. The caloric deficit calculated from the observed weight loss could be accounted for entirely by the estimated decrease in intake in 22 of the 48 patients who ate less postoperatively. Moreover, measured fat malabsorption accounted for only 31% of the observed weight loss in those who ate more postoperatively and 21% in those who ate less. We conclude that a decrease in caloric intake, along with malabsorption, is an important factor in the long term postoperative weight loss (1-9 months) after jejunoileal bypass for obesity.

Body Weight↗

PubMed1977

Methods for the calculation of weight loss by water evaporation from small biopsy specimens.

The rate of loss of weight by water evaporation was obtained for biopsies taken from lamprey muscle, and this was related to the original weight of each sample. Hence, two alternative methods are proposed for the correction of small biopsy weights to allow for this evaporation in air. It is suggested that these methods may permit good approximations for corrections in similar conditions to those used, and that the methods for evaluating empirical coefficients may be applied elsewhere to allow for other situations.

Biopsy, Needle↗

PubMed1978

Double blind clinical trial of mazindol on weight loss blood glucose, plasma insulin and serum lipids in overweight diabetic patients.

Mazindol, a drug with tricyclic structure unrelated to amphetamine and other anorectic drugs, has been used as an anorectic agent in a double blind clinical trial at a dose of 2 mg/day for 12 week (mazindol v. s. placebo), associated with a 1000 calorie diet on 46 obese diabetic patients. Thirty seven patients completed the trial with no significant difference between the two groups in the drop-out population; mazindol was well tolerated. In the mazindol-treated group the mean weight loss was 13.5 kg (22.3%) which was significantly greater (p less than 0.001) than in the placebo treated group where the mean weight loss was 4.2 kg (9.8%). Comparing the two groups after the 12 week trial, decrease in fasting blood glucose, serum insulin and triglycerides was not significant. In the mazindol-treated group a significant decrease of serum cholesterol, triglycerides and of the mean area under the curve of insulinemia during the OGTT has been observed. In the placebo treated group only serum triglycerides decreased significantly. The variations of plasma insulin and serum cholesterol were found to be correlated to the magnitude of weight loss. In conclusion mazindol is an effective drug for weight loss on the whole well tolerated but without specific properties on metabolism.

Blood Glucose↗

PubMed1978

Clonidine antagonizes naloxone-induced suppression of conditioned behavior and body weight loss in morphine-dependent rats.

Clonidine's action on naloxone (Nx)-induced suppression of fixed-ratio (FR15) responding and body weight loss was studied in morphine (M)-dependent rats. Clonidine (10--70 microgram/kg IP) injected 30 min prior to the behavioral session resulted in a dose-related suppression of operant behavior in M-naive animals. A small, but significant decrease (3--5%) in body weight was also observed at the higher doses of clonidine. More than twice as much weight loss, associated with diarrhea, was obtained when Nx (5.0 mg/kg IP) was administered to M-dependent animals. When clonidine (10--50 microgram/kg IP) was administered prior to Nx, in M-dependent animals, the withdrawal-induced disruption of operant responding was significantly attenuated. Concurrent weight loss, which was significantly antagonized by 1 microgram clonidine/kg, was decreased by as much as 40 percent. The degree of amelioration of withdrawal that was observed appeared to be inversely related to the dose of clonidine. The optimal dose was 10 microgram/kg, which by itself was only partially behaviorally active. At higher doses, clonidine's blocking properties were less apparent as a result of its own potent behavioral suppressant and diuretic effects which masked its capacity to attenuate withdrawal. The data are discussed in relation to the application of operant technics for assessing drug treatment(s) designed to alter the severity of narcotic withdrawal.

Animals↗

PubMed1976

[Prenatal weight loss in the infant (author's transl)].

Hillemanns and coworkers established, that infants born after induced labor were heavier, on the average, than those from a control group; who were born after spontaneous labor. Since it was postulated, that a weight loss preceded the onset of spontaneous labor, the birth weight and length of 444 infants born after induced labor and 70 infants born via a primary cesarean section was compared with a control group of 1,028 uncomplicated births via spontaneous labor. Thirty seven post term infants were also included in the study. The birth weight and length of infants after induced labor or delivered by primary cesarean section significantly higher than those in the control group. The post term infants were also significantly longer, but their weight was not significantly lower, than that in the control group. The major differences could not be accounted for by varying periods of gestation nor could they be accounted for by the special conditions of induced labor or cesarean section. Therefore, the only possibility remaining is that a weight loss precedes spontaneous labor. This may possibly be explained by the reduction in the relative water content which begins before birth and continues through the newborn period or by a relative placenta insufficiency. The infant weight loss and loss of amniotic fluid after the thirtyeighth week of pregnancy refutes the theory, that birth is induced by a stretching of the uterine wall. The possibility is discussed, that the onset of labor is influenced by a corresponding relief from tension such as that, which occurs following a premature rupture of the fetal membranes.

Birth Weight↗

PubMed2026

Effectiveness of Internet-Delivered Cognitive Behavioural Therapy (ICBT) in Improving Weight-Loss and Psychosocial Well-Being Among Adults With High BMI: A Systematic Review.

AIM: To examine the effectiveness of Internet-delivered Cognitive Behaviour Therapy (ICBT) in improving psychosocial well-being and promoting weight-loss in adults ≥ 18 years with BMI ≥ 25 kg/m2. BACKGROUND: Global obesity engenders significant physical and psychosocial health consequences. Second-wave ICBT focused on restructuring negative thoughts and behaviours has been explored as a potential intervention for elevated BMI and mental health concerns, but its effectiveness remains to be fully established, making further evaluation essential. METHODS AND DATA SOURCES: Eight databases were searched from inception to January 2025 for randomised controlled trials (RCTs), including participants ≥ 18 years with BMI ≥ 25 kg/m2 and second-wave ICBT evaluating BMI, weight, depression, eating behaviours, and self-esteem. This review followed PRISMA 2020. Study quality was assessed using the Cochrane Risk of Bias (ROB 2) and GRADE. Data were extracted using a modified Cochrane form. Random-effects meta-analysis calculated Standardised Mean Differences (SMD) with 95% confidence intervals, with subgroup analyses exploring heterogeneity. RESULTS: Nine trials with 2278 participants were included. Significant improvements were seen in BMI, weight, and depressive symptoms while self-esteem effects were small and non-significant. Compared with passive controls, ICBT showed greater improvements in BMI and weight, whereas differences versus active control were smaller and inconsistent. Face-to-face CBT demonstrated superior outcomes for depression and self-esteem. Male-tailored interventions showed greater improvements. Shorter programmes yielded larger short-term weight loss, while longer programmes supported more sustained effects. Narrative synthesis indicated improvements in emotional and external eating, with increased mindful and restrictive eating behaviours. CONCLUSION: ICBT improved weight, BMI, and depressive symptoms, with limited evidence for self-esteem. Male-tailored interventions and longer programmes may enhance sustainable outcomes. IMPACT: Future ICBT programs should integrate strategies targeting sustainable weight loss and psychosocial well-being to support long-term outcomes. NO PATIENT OR PUBLIC CONTRIBUTION: Patients or members of the public were not involved, as this study synthesised previously published data. TRIAL REGISTRATION: PROSPERO registration number: CRD42024497961.

Humans↗

PubMed2026

Weight Loss without Food Intake Suppression through Size-Dependent Retention of Anti-Inflammatory Nanomedicines.

Obesity is a risk factor for high-mortality health conditions, including cardiovascular diseases and type 2 diabetes, which makes the advancement of efficacious and safe weight loss therapies a high priority in pharmacology. The causal link between obesity and its comorbid conditions is believed to be a chronic state of inflammation originating within adipose tissue, with macrophages playing central roles, an axis that is not targeted directly by current therapies. Here, we use nanocarriers to deliver an anti-inflammatory glucocorticoid receptor agonist to adipose tissue macrophages and report the impact of size on therapeutic effect. Three dextran nanocarriers between 4-30 nm in hydrodynamic diameter released molecular drug cargo at equivalent rates and exhibited similar biological potency in vitro. In vivo in a mouse model of obesity, body weight and body fat were reduced in a size-dependent manner after 2-4 weeks of treatment. Unlike current clinical pharmacotherapies for weight loss, these body composition changes were not associated with changes in food intake. Greater retention of larger dextran nanocarriers in visceral adipose tissue appears to elicit a local change to promote browning by increasing mitochondrial abundance and lipid droplet fragmentation. Further development of this platform may result in a safe and potent modulator of adipose tissue in the state of obesity without direct action on nutrient intake to address malnutrition and lean body mass deficiencies observed with current weight loss pharmacotherapies.

Animals↗

PubMed1979

Effects of a combined behavioral and pharmacological program on weight loss.

The effects of an 'anorectic' drugs as an adjunct to a behavioral weight-loss programme were investigated. Four groups of 20 began an initial two weeks of instruction. Groups 1, 2, and 3 were instructed in a behavioral programme utilizing a food diary, stimulus control techniques, and reinforcement. Group 4 was instructed in a relaxation programme. Group 1 took phentermine resin 30 mg for eight weeks, followed by a placebo for eight. Group 2 took placebo for eight and phentermine for eight. Group 3 took placebo for 16. Group 4 took placebo for eight and phentermine for eight. All groups were followed for an additional eight weeks. A significant number of subjects in all behavioral groups achieved some weight loss. (A significant difference among the mean percentage body weight reduction for the three behavioral groups was also found.) In addition, a group of 'slow losers' who initially lost less than one half-pound (0.2 kg) per week and were subsequently placed on phentermine lost significantly more weight than a similar group which continued on placebo. These differences were maintained for 24 weeks.

Behavior Therapy↗

PubMedDate not supplied

Serum thyroid hormone concentrations and weight loss relationships in eight obese women during semistarvation.

Eight obese female patients were studied over a period of 15 days whilst on 300 kcal diet. Serum levels of thyroxine and free throxine index were not altered significantly by semistarvation. A TRH test performed before and after the diet showed no appreciable change. Weight loss was intially rapid but later slowed despite good patients compliance. Serum concentrations of T 3 and reverse T 3 (rT3) early decreased (p less than 0.01) and increased (p less than 0.05) respectively, but returned towards control levels even before discontinuation of semistarvation. There was a positive correlation between the percentage decrease in body weight and the percentage increase in serum rT 3 (p less than 0.001), and a negative correlation between decrease in body weight and decrease in serum T 3 (p less than 0.001). Our results do not suggest that the variations in serum triiodothyronines limit the weight loss; it is probable, on the contrary, that the weight loss promotes the observed variations in thyroid hormones by as yet unknown adaptive metabolic forces.

Adult↗