Discontinuing semaglutide after weight loss: strategy for weight maintenance and a possible new side effect.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) facilitate weight loss. Weight regain off therapy is concerning. We reported the case of a 35-year-old male prescribed oral semaglutide with 22.7 kg weight loss over 120 days. Herein, we describe the clinical course when discontinuing GLP-1 RA therapy, one approach to maintaining weight loss after discontinuation, and a possible new side effect. At day 120, we continued oral semaglutide 7 mg daily, down from 14 mg, for weight maintenance with subsequent weight regain. We re-increased semaglutide to 14 mg/day with weight re-loss within 1 month and weight maintance for a year. We then discontinued semaglutide; weight loss was maintained for 6 months. The patient reported lactose intolerance ∼13 months before starting semaglutide. During semaglutide therapy, the patient reported worsened lactose intolerance and new gluten intolerance. Food allergy/celiac testing were negative. Intolerances did not improve with semaglutide discontinuation. Six months after semaglutide discontinuation, the patient was diagnosed with small intestinal bacterial overgrowth, possibly worsened by semaglutide. Factors potentially supporting weight maintenance were early drug treatment for new-onset obesity, non-geriatric age, strength training, and diet modification. The case highlights tailoring approaches to maintain weight loss without GLP-1 RAs. Trials are needed to optimize weight maintenance strategies.

An observational study on nutrition status in gastric cancer patients receiving ramucirumab plus taxane: BALAST study.

Limited data are available regarding the efficacy of nutrition support in advanced gastric cancer (AGC) patients receiving a standard second-line combination chemotherapy. The BALAST study is conducted as a prospective, multicenter observational study to evaluate the efficacy of nutrition support for patients with AGC treated with ramucirumab plus taxane as second-line treatment. As part of the routine care, patients who are malnourished or at risk of malnutrition will receive nutrition support from dietitians. We will enroll a total of 26 patients to estimate weight control rate at 12 weeks as primary end point. This study will generate valuable data reinforcing the role of nutrition support therapy for AGC patients receiving second-line chemotherapy.

Lay abstract Various guidelines recommend that nutrition support therapy should be considered if cancer patients are malnourished or at risk of malnutrition. Several studies have revealed that body weight loss, which is an important factor in determining the nutrition status, may predict survival during second-line standard chemotherapy with ramucirumab and a taxane for advanced gastric cancer (AGC) patients. However, limited data are available regarding the efficacy of nutrition support in AGC patients receiving ramucirumab and a taxane. This study is conducted as a prospective, multicenter observational study to evaluate the efficacy of nutrition support for Japanese patients with AGC treated with ramucirumab and a taxane. This study will generate valuable data reinforcing the role of nutrition support therapy for AGC patients in second-line treatment. Clinical trial registration: UMIN000037867.

Caloric restriction, physical exercise, and CB1 receptor blockade as an efficient combined strategy for bodyweight control and cardiometabolic status improvement in male rats.

Obesity is critically associated with the development of insulin resistance and related cardiovascular and kidney diseases. Several strategies for weight loss have been developed but most of them exhibit a post-intervention rebound effect. Here, we aimed to design combined weight-loss strategies of caloric restriction, physical exercise, and administration of a CB1 receptor blocker to inhibit food intake that also accomplish the objectives of lost-weight maintenance and improvement of cardiovascular and renal function. Diet-induced obesity (DIO) was generated in Sprague Dawley rats for 12 weeks to test the effects of single or combined strategies (i.e. caloric restriction, mixed training protocol, and/or administration of appetite suppressant) on caloric intake, body weight, cardiovascular and renal functionality resulting from a weight-loss intervention period of 3 weeks followed by 6 weeks of weight maintenance. Consumption of a high-fat diet (HFD) caused a significant increase in body weight (5th week of the experimental period) and led to the development of insulin resistance, cardiovascular, and renal alterations. The different interventions tested, resulted in a significant body weight loss and improved glucose metabolism, aerobic capacity, electrocardiographic parameters, vascular expression of adhesion molecules and inflammatory mediators, and renal functionality, reaching values similar to the control normocaloric group or even improving them. Successful maintenance of lost weight was achieved along a 6-week maintenance period in addition to adequate health status. In conclusion, the weight-loss and maintenance intervention strategies tested were efficient at reversing the obesity-related alterations in body weight, glucose metabolism, aerobic capacity, cardiovascular and renal functionality. The beneficial action was very consistent for caloric restriction and physical exercise, whereas administration of a CB1 receptor blocker complemented the effects of the prior interventions in some parameters like body weight or aerobic capacity, and showed specific actions in renal status, increasing glomerular filtration rate and diuresis. Overall, the novelty of our study relies on the easy implementation of combined strategies for effective weight management that resulted in significant health benefits.

A combined healthy strategy for successful weight loss, weight maintenance and improvement of hepatic lipid metabolism.

Obesity is critically related with the development of metabolic and pathophysiological alterations among which non-alcoholic fatty liver disease (NAFLD) is of especial relevance. Although there are numerous strategies to successfully treat obesity, the prevention of weight regain still remains challenging for individuals who have undergone weight loss programs. In such context, diet and physical activity are considered essential for the regulation of body weight and lipid metabolism. In this study, rats were fed a high-fat diet (HFD) to induce obesity and alterations in hepatic lipid metabolism. Obese rats were then treated with single or combined strategies of caloric restriction, physical exercise, and/or pharmacological treatment with an appetite suppressant, to lose weight, reverse the obesity-related alterations in hepatic morphology and lipid metabolism and maintain the beneficial effects of the interventions used. HFD induced excess body weight, hepatic steatosis, altered fatty acid profile, dysregulated gene expression of lipogenic and lipolytic enzymes, as well as plasma markers of liver damage, and modifications in liver antioxidant enzyme activity. Such alterations were ameliorated by caloric restriction in combination with a mixed training protocol and/or food-intake inhibitor administration during a weight loss intervention period of 3 weeks, and the beneficial effects remained after 6 weeks of weight maintenance, with some interesting interactions observed. In conclusion, weight loss strategies assayed were efficient at correcting the obesogenic action of a HFD and related alterations in hepatic functionality through different molecular mechanisms. The beneficial effects were also evident along the post-intervention maintenance period to avoid body weight regain.

Double jeopardy: a review of weight gain and weight management strategies for psychotropic medication prescribing during methadone maintenance treatment.

Methadone maintenance treatment (MMT) is an important treatment tool for the opioid epidemic. One challenge is that many persons who present for MMT also have co-occurring psychiatric disorders. Individually, both methadone and psychiatric medications carry risk of weight gain. Therefore, concurrent prescribing of methadone and psychiatric medications places dual diagnosis patients at even greater risk. As a parallel obesity epidemic grows, results from clinical trials assessing weight gain and weight management strategies among MMT and psychiatric patients can both inform and guide clinical practice. This study reviews findings from a literature search for recent clinical trials that focused on weight gain and weight management strategies during MMT with concurrent psychotropic medication use. While several studies have documented weight gain during MMT and psychotropic medication treatment, this study failed to identify recent work that explored concurrent prescribing. Most weight management strategies involved the use of additional medications and available data suggests that MMT and concurrent use of psychotropic medications increases the risk for obesity. More robust research is needed on weight gain and potential mitigation strategies when these treatment modalities are jointly utilized. Clarification of underlying biological mechanisms and development of non-pharmacological interventions merit further consideration.

The future of weight management in pharmacy education - Perspectives of new generation pharmacists.

INTRODUCTION: Over recent years, the profession of pharmacy has transitioned towards providing more individualised patient care services. In this context, community pharmacy has proven to be an excellent facilitator for weight management programs. However, education on weight management in pharmacy undergraduate curricula is often lacking. The perspectives of early career pharmacists on their perceived role in weight management services and their associated educational needs can inform curricula review. METHODS: In-depth, semi-structured interviews were conducted with 20 final year pharmacy students of The University of Sydney and five early career pharmacists from the greater Sydney, Australia area. Interviews were recorded, transcribed, and analysed for themes emerging. RESULTS: Participants were positive about their perceived role in providing weight management services. They regarded a program not based on commercial products as most suitable for pharmacy-delivered weight management services. However, some barriers were identified, such as lack of training and communication skills related to weight management. Participants requested more educational resources to ensure the delivery of high quality weight management services. DISCUSSION: Methods to enhance (future) pharmacists' knowledge of weight management services could include case-based learning, enhancement of communication skills, and the development of suitable guidelines. CONCLUSIONS: Participants perceived a clear role for themselves in providing weight management services in community pharmacies. However, the current educational system does not meet their requirements to prepare them for this role. A hands-on approach in education on weight management and appropriate communication skills should be introduced in pharmacy curricula to ensure future pharmacists are well prepared to deliver weight management services.

Unhealthy Weight Management Practices and Non-medical Use of Prescription Drugs.

INTRODUCTION: Non-medical use of prescription drugs (NMUPD) has reached epidemic proportions in the U.S. With approximately one in five high school students engaging in NMUPD, it is important to understand behavioral correlates. METHODS: Data were combined from the 2011 and 2013 cycles of the Youth Risk Behavior Survey, a nationally representative, cross-sectional survey. After restricting the analytic sample to students who reported a weight loss goal of either staying the same weight or losing weight, logistic regression models were used to estimate adjusted prevalence ratios and 95% CIs for associations between unhealthy weight management practices (UWMPs) and lifetime NMUPD. Individual UWMPs-fasting; taking diet pills, powders, or liquids without a doctor's advice; and vomiting or taking laxatives-and total number of UWMPs were examined. Data were analyzed in 2016. RESULTS: UWMPs were more prevalent among female students (21.1% vs 10.7% for fasting; 7.5% vs 5.2% for taking diet pills, powders, or liquids; and 7.6% vs 3.2% for vomiting or taking laxatives). Significant associations between individual UWMPs and NMUPD and between the number of UWMPs and NMUPD were observed. DISCUSSION: UWMPs were associated with NMUPD. Health educators in the school setting, as well as other health professionals who provide services to an adolescent population, can focus on healthy weight management strategies, and other substance-specific messages. CONCLUSIONS: The association between UWMPs and NMUPD may reflect a constellation of problem behaviors exhibited among some adolescents.

Safety and Efficacy of Banaba-Moringa oleifera-Green Coffee Bean Extracts and Vitamin D3 in a Sustained Release Weight Management Supplement.

This 60-day, 30-subject pilot study examined a novel combination of ingredients in a unique sustained release (Carbopol matrix) tablet consumed twice daily. The product was composed of extracts of banaba leaf, green coffee bean, and Moringa oleifera leaf and vitamin D3. Safety was assessed using a 45-measurement blood chemistry panel, an 86-item self-reported Quality of Life Inventory, bone mineral density, and cardiovascular changes. Efficacy was assessed by calculating a body composition improvement index (BCI) based on changes in dual energy X-ray absorptiometry measured fat mass (FM) and fat-free mass (FFM) as well as between the study group (SG) and a historical placebo group. No changes occurred in any blood chemistry measurements. Positive changes were found in the Quality of Life (QOL) inventory composite scores. No adverse effects were observed. Decreases occurred in FM (p = 0.004) and increases in FFM (p = 0.009). Relative to the historical placebo group, the SG lost more FM (p < 0.0001), gained more FFM (p = <0.0001), and had a negative BCI of -2.7 lb. compared with a positive BCI in the SG of 3.4 lb., a 6.1 discordance (p = 0.0009). The data support the safety and efficacy of this unique product and demonstrate importance of using changes in body composition versus scale weight and BMI.

The Impact of Gender and Protein Intake on the Success of Weight Maintenance and Associated Cardiovascular Risk Benefits, Independent of the Mode of Food Provision: The DiOGenes Randomized Trial.

OBJECTIVE: Maintenance of weight loss and associated cardiovascular benefits after following energy-restricted diets is still a challenging field, and thorough investigation is needed. The present research aimed to determine the role of protein and gender in relation to two different intervention models related to food supply, in a weight maintenance trial. SUBJECTS AND METHODS: The DiOGenes trial was a long-term, multicenter, randomized, dietary intervention study, conducted in eight European countries (Clinical Trials.gov, NCT00390637), focusing on assessing the effectiveness of weight maintenance over 6 months. This secondary analysis intended to evaluate the different benefits for weight maintenance and cardiometabolic markers of two dietary advice delivery models: "shop + instruction intervention" vs "instruction-alone intervention," which were further categorized for gender and macronutrient intake. RESULTS: The weight maintenance intervention based on different macronutrient intake showed, independently of the advice delivery model, in both sexes that higher protein consumption was more effective for weight stability, showing better results in obese women (low protein: 1.65 kg in males and 0.73 Kg in females vs high protein: 1.45 kg in males and -0.93 Kg in females) . Measurements concerning cardiovascular risk markers from subjects on both structured models produced similar trends in the subsequent follow-up period, with a lower rebound in women for most of the markers analyzed. CONCLUSION: The reported dietary benefits for weight sustainability should be ascribed to the macronutrient distribution (higher protein diets) rather than to the structured mode of delivery. Higher weight regain in males was noted, as well as a metabolic divergence attributable to the sex, with a better biochemical outcome in women.

Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults.

OBJECTIVE: The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults. DESIGN: To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults. RESULTS: Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group. CONCLUSIONS: These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans. TRIAL REGISTRATION NUMBER: NCT00750438.

Effects of rye bread enriched with green tea extract on weight maintenance and the characteristics of metabolic syndrome following weight loss: a pilot study.

We examined whether the incorporation of green tea extract enriched rye bread (GTRB) into the diet can improve weight loss (WL) maintenance and control of abnormalities linked to metabolic syndrome (MS). A total of 55 obese men and women (mean age: 53.0±7.0 years, body mass index: 35.0±5.5 kg m(-2)) were recruited. The study had a single-blind randomized study design and consisted of an 8-week WL phase with low-energy calorie diet, followed by a 12-week weight maintenance (WM) phase. During the WM phase, the subjects were randomized into two groups, receiving either the control rye bread (control group) or the GTRB (intervention group). The ingestion of 280 and 360 g GTRB provided daily totals of 123.2 and 158.4 mg caffeine, and 188.3 and 242.1 mg of epigallocatechin gallate, for women and men, respectively. After the WL phase, subjects lost 7.3±3.1 kg of their baseline body weight. GTRB intake did not significantly influence the maintenance of WL, high-density lipoprotein-cholesterol, triglycerides, and glucose concentrations. Although, it resulted in significant differences (mean difference [95% confidence interval]) between the treatment groups in the maintenance of waist circumference (-1.22 cm [-2.4, -0.02; P=.04]), the results were not clinically meaningful. Nevertheless, the ingestion of GTRB led to the maintenance of lower blood pressure (BP), also the proportion of subjects fulfilling the criteria of MS after the WM phase was lower in the intervention group than in the control group. Although GTRB consumption did not improve significantly the WL maintenance, it resulted in a better control of BP.