What influences patient decisions when selecting an obesity treatment?

Objective: The objectives of this study were to understand patient preferences for obesity treatments, to describe how patients choose treatment options, and what factors influence their decisions. Methods: This participatory action research used purposeful sampling to recruit 10 patients with complications of obesity. Photovoice was used as the qualitative research methodology. Recruitment took place in specialist clinics for metabolic dysfunction-associated steatotic liver disease, diabetes mellitus, hypertension, and chronic kidney disease. Two males and eight females aged 18-75 years, with a BMI greater than 35 kg/m2 were recruited. Participants watched a 60-min â€‹video explaining nutritional, pharmacological, and surgical therapies in equipoise. Data was collected using photographs with a disposal camera followed by one-to-one semi-structured interviews. Afterward, this analysis utilised reflective thematic analysis. Results: Five main themes were identified that influenced patients' decisions when selecting an obesity treatment: 1] Accessibility issues, 2] Polypharmacy, 3] Fears around future health 4] Lack of Support 5] Information Mismanagement. Conclusion: The themes identified in this study represent the patients' voices for those living with obesity complications and what influences their decisions on treatment options. The findings underscore the need for a holistic and patient-centred approach to the management of obesity and its associated complications. Patient-centred care including knowledge, health literacy, support, and participation is essential to providing effective care for patients with obesity to make decisions between treatment options.

Metabolic adaptation following gastric bypass surgery: results from a 2-year observational study.

BACKGROUND/OBJECTIVES: Metabolic adaptation is the lowering of basal metabolic rate (BMR) beyond what is predicted from changes in fat mass (FM) and fat-free mass (FFM) and may hamper weight-loss progression. It is unclear whether metabolic adaptation occurs following gastric bypass surgery (GBP) and if it persists. The aim of this study was to evaluate the reduction in BMR that is not explained by changes in body composition in patients following GBP compared to a weight-stable comparator group. SUBJECTS: Thirty-one patients [77.4% female; mean BMI 45.5(SD 7.0) kg/m2; age 47.4(11.6)y] who underwent GBP, and 32 time-matched comparators [50% female; BMI 27.2(4.6) kg/m2; age 41.8(13.6)y) were evaluated at 1-month pre-surgery, 3-, 12- and 24-months post-surgery. METHODS: BMR was measured under standardised residential conditions using indirect calorimetry and body composition using DXA. Linear regression analyses assessed metabolic adaptation post-surgery. RESULTS: After surgery, patients lost a quarter of their body weight [-25.6%(1.8%); p < 0.0001] consisting mainly of FM (4:1 FM to FFM loss ratio) at 24-months post-surgery. Absolute BMR (MJ/d) reduced by 25.7% at 24-months post-surgery with values becoming similar to the comparator group from 3-months post-surgery. Positive associations were observed between changes in BMR and changes in FFM and FM (P < 0.03). Metabolic adaptation was present in patients during the 1) rapid weight loss phase (6.9 kg/month at 3-months post-surgery) (p = 0.011), 2) slower weight loss phase (1.6 kg/month from 3 to 12-months post-surgery) (p < 0.0001), and, 3) weight maintenance phase (24-months post-surgery) (p = 0.00073). However, the degree of metabolic adaptation observed in GBP patients was similar to the weight-stable comparator group (no metabolic adaptation) from 12-months post-surgery onwards (3-months; p = 0.01, 12-months; p = 0.26, 24-months post-surgery; p = 0.70). CONCLUSION: These results suggest that there is a potential biological mechanism of surgery that attenuates the expected postoperative downregulation in BMR thus helping GBP patients maintain weight loss.

Semaglutide and blood pressure: an individual patient data meta-analysis.

BACKGROUND AND AIMS: Randomized clinical trials (RCTs) assessing semaglutide reported reductions of systolic blood pressure (SBP) in trial populations with baseline blood pressure in the normotensive range. This study aimed to determine whether this SBP reduction is greater in hypertensive groups. METHODS: Individual patient data (IPD) from three RCTs examining the effect of semaglutide 2.4 mg on body weight over 68 weeks were included. Trial participants were categorized according to a hypertension diagnosis, treatment or baseline measurement (HTN), baseline SBP > 130 mmHg (HTN130) or >140 mmHg (HTN140), and those with apparent resistant hypertension (RH). The primary analysis compared the in-trial change in SBP in the semaglutide and placebo arms. Alterations of anti-hypertensive medications were quantified by treatment intensity score and compared between arms. These analyses were performed using analysis of covariance. RESULTS: Overall, 3136 participants were included. The difference in SBP change between the treatment (n = 2109) and placebo (n = 1027) groups was -4.95 mmHg [95% confidence interval (CI) -5.86 to -4.05] overall. This difference was -4.78 mmHg (95% CI -5.97 to -3.59) for HTN, -4.93 mmHg (95% CI -6.75 to -3.11) for HTN130, -4.09 mmHg (95% CI -7.12 to -1.06) for HTN140, and -3.16 mmHg (95% CI -8.69-2.37) for RH. Reduction in SBP was mediated substantially by weight loss. The anti-hypertensive treatment intensity score decreased for those on semaglutide compared to placebo (-0.51; 95% CI -0.71 to -0.32). CONCLUSIONS: This IPD analysis of three large RCTs found blood pressure reductions with semaglutide in participants with hypertension that were similar to those seen in all trial participants. This finding may in part be due to concurrent reductions to anti-hypertensive medications. These results suggest that semaglutide is a useful adjunctive treatment for patients with hypertension and obesity.

"What would be left of me?" Patient perspectives on the risks of obesity treatment: An innovative health initiative stratification of obesity phenotypes to optimise future obesity therapy (IMI2 SOPHIA) qualitative study.

Background: The uptake of obesity treatments remains disproportionally low in people living with the disease, even with the advent and availability of GLP-1 agonists in recent years. Efforts to understand this discrepancy have centred on literature syntheses and Healthcare Professionals' (HCPs) perspectives on the barriers to obesity treatment. This study focuses on patient perspectives on the risks of obesity treatment. Method: This qualitative study consisted of online focus groups with 30 adults with obesity from Europe and North America. The focus group discussions were recorded, transcribed verbatim and analysed thematically. Results: Patients identified three risks associated with obesity treatment: (a) the risk that they can't access treatment; (b) the risk that they would fail to meet treatment expectations - their own, their HCPs and societal expectations, and (c) the risk that the treatment would be 'successful' but that they would lose their sense of self, their coping mechanisms and identity along with weight. Conclusion: Understanding patient concerns about the risks of obesity treatment is essential to addressing obesity treatment inertia.

Laxative Properties of Microencapsulated Oleic Acid Delivered to the Distal Small Intestine in Patients with Constipation after Bariatric Surgery or Treatment with Glucagon-Like- Peptide 1 Analogues.

BACKGROUND: Constipation is prevalent after bariatric surgery and glucagon-like-peptide 1 (GLP-1) analogues. Increasing fat content in the distal small intestine and colon can enhance colonic peristalsis, potentially alleviating symptoms of constipation. AIM: We investigated whether oleic acid can ameliorate constipation in patients undergoing bariatric surgery or receiving GLP-1 analogues. METHODOLOGY: Fourteen adults with chronic constipation according to Rome IV criteria following bariatric surgery or GLP-1 analogues were on stable treatment for constipation for more than 4 weeks. This randomized double-blind crossover trial compared microcapsules containing 21.25 g of oleic acid delivered in the distal small intestine or the stomach. The primary outcome was changed in the number of bowel motions over 24 h. Exploratory endpoints included alterations in straining, diarrhoea, faecal leakage over 24 h and hunger, fullness, nausea and calorie intake for the 3 h after ingesting the microcapsules. FINDINGS: Receiving oleic acid into the distal small intestine increased number of bowel movements per day (2.5 vs 1.1, p = 0.009) and caused softer stool consistency (p = 0.03). 9/14 of the control group passed motions and 13/14 of the intervention group passed motions in 24 h (p = 0.059). No significant differences were observed in straining (p = 0.65), rapid bowel movements (p = 0.08), accidental leakage (p = 0.32), hunger, fullness, nausea or food intake between the groups (all p > 0.05). There were no disparities in safety profile between groups. CONCLUSION: Microcapsules containing oleic acid delivered to the distal small intestine appear to be a safe and effective relief from chronic constipation in patients undergoing bariatric surgery and/or receiving GLP-1 analogues.

Resmetirom and Metabolic Dysfunction-Associated Steatohepatitis: Perspectives on Multidisciplinary Management from Global Healthcare Professionals.

PURPOSE OF REVIEW: The approval of resmetirom brings great hope to patients with metabolic dysfunction-associated steatohepatitis (MASH). The purpose of this review is to explore its impact on the global health environment. The implementation of multidisciplinary management MASH is proposed. RECENT FINDINGS: Resmetirom has benefits in the treatment of MASH, and its safety and effectiveness have been studied. The adverse events (AEs) need to be noticed. To improve patient outcomes, a multimodal approach with medication such as resmetirom, combined with metabolic and bariatric surgery (MBS) and lifestyle interventions can be conducted. MASH, a liver disease linked with obesity, is a challenging global healthcare burden compounded by the absence of any approved pharmacotherapy. The recent conditional approval by the Food and Drug Administration (FDA) in the United States of resmetirom, an oral, liver-directed, thyroid hormone receptor beta-selective agonist, marks a significant milestone, offering a treatment option for adults with non-cirrhotic MASH and who have moderate to advanced liver fibrosis. This narrative review discusses the efficacy and safety of resmetirom and its role in the therapeutic landscape of MASH treatment. Despite the promising hepatoprotective effect of resmetirom on histological liver endpoints, its use need further research, particularly regarding ethnic differences, effectiveness and cost-effectiveness, production scalability, social acceptance and accessibility. In addition, integrating resmetirom with other multidisciplinary therapeutic approaches, including lifestyle changes and MBS, might further improve clinical liver-related and cardiometabolic outcomes of individuals with MASH. This review highlights the importance of a comprehensive treatment strategy, supporting continued innovation and collaborative research to refine treatment guidelines and consensus for managing MASH, thereby improving clinical patient outcomes in the growing global epidemic of MASH. Studies done to date have been relatively short and ongoing, the course of the disease is highly variable, the conditions of various patients vary, and given this complex clinical phenotype, it may take many years of clinical trials to show long-term benefits.

Reformulating ice cream to improve postprandial glucose response: an opportunity for industry to create shared value.

Ultra-processed foods are associated with metabolic dysfunction and driving chronic diseases. The Metabolic Matrix is a tool used to reformulate products to promote positive metabolic outcomes. The Kuwait Danish Dairy Company (KDD) has used this tool to develop a no-added-sugar products. This clinical trial tested the glycaemic response of a no-added-sugar ice cream in individuals with type 2 diabetes. The hypothesis was that the no-added-sugar ice cream would have a substantially better postprandial glycemic response than conventional ice cream in patients with type 2 diabetes. In this randomized cross over designed study, postprandial glycemic response was measured after 300 grams of no-added-sugar ice cream or normal ice cream was consumed. Despite similar composition and palatability, the postprandial responses were better with the no-added sugar ice cream, albeit that the natural sugar in the product still resulted in a marked postprandial glycaemic response. This finding emphasizes the necessity of clearly communicating to both patients and healthcare professionals that "no-added-sugar" does not equate to "zero total sugar." The path to improved metabolic health involves not only product improvement but also transparent messaging to enable informed dietary choices. Reformulation resulting in palatable no-added sugar products provides an opportunity for companies to Create Shared Value by addressing the important social problems such as obesity and type 2 diabetes, by creating scalable solutions, that are profitable. Clinical trial registration:ClinicalTrials.gov, identifiers NCT06135935.

Liver fibrosis and liver stiffness in patients with obesity and type 1 diabetes.

AIM: To compare hepatic stiffness and fat fraction in patients with obesity and type 1 diabetes (T1D) with type 2 diabetes (T2D) with a similar body mass index (BMI). METHODS: In this prospective cross-sectional study, 90 participants with T1D (BMI 30.5 ± 4.5 kg/m2; diabetes duration 20.5 ± 9.8 years; HbA1c 8.2% ± 1.4%) and 69 with T2D (BMI: 30.8 ± 4.6 kg/m2; diabetes duration: 11.7 ± 7.8 years; HbA1c: 7.3% ± 1.4%) were included. Liver fat fraction and stiffness were examined by magnetic resonance imaging and elastography, respectively. Logistic regressions were used to evaluate associations with biomedical variables. RESULTS: The mean liver stiffness score in patients with obesity and T1D was 2.2 ± 0.5 kPa, while in T2D it was 2.6 ± 0.8 kPa (P < .001). The liver fat fraction in patients with obesity and T1D was 3.7% ± 6.3%, and in T2D it was 10.6% ± 7.9% (P < .001). Metabolic dysfunction-associated steatotic liver disease (MASLD) was present in 13.3% of patients with T1D and in 69.6% of patients with T2D, whereas fibrosis was suggested in 7.8% of patients with T1D and in 27.5% of patients with T2D. Liver stiffness was four times higher in patients with T2D compared with those with T1D (odds ratio = 5.4, 95% confidence interval: 2.1-13.6, P < .001). Aspartate transaminase (AST), alanine transaminase, gamma-glutamyl transferase (GGT), triglycerides and the android-to-gynoid ratio were associated with elevated fat fraction in both cohorts. AST and GGT were associated with elevated liver stiffness in both cohorts. CONCLUSIONS: Patients with obesity and T1D had lower liver fat and liver stiffness compared with those patients with T2D, despite similar levels of BMI, a longer duration of diabetes and worse glycaemic control.

Patient perspectives on personalised medicine for obesity: An IMI2 SOPHIA Study.

OBJECTIVE: Personalised medicine is seen as an exciting opportunity to improve the health outcomes of people with obesity. As research on phenotyping and personalised treatment for obesity rapidly advances, this study sought to understand patient preferences and perspectives on personalised medicine for obesity. METHODS: A participatory world café methodology was used to garner the perspectives of people living with obesity on the potential opportunities and limitations associated with a personalised approach to obesity risk identification and treatment. Data were recorded by participants on tablemats and analysed thematically using thematic analysis. RESULTS: Patients expressed the hope that personalised medicine for obesity would reduce stigma, support understanding of obesity as a disease, and improve treatment outcomes and acceptance. They also expressed concern about the accuracy of personalised medicine for obesity, its implications for insurance and that further advances in individual, personalised medicine, would detract attention from social, environmental, economic and psychological drivers of obesity. CONCLUSIONS: This study highlights how patients are generally very optimistic about the potential for personalised obesity medicine but also raise a number of legitimate concerns that will be of interest to clinicians, industry, and policy makers.

Harnessing the melanocortin system in the control of food intake and glucose homeostasis.

The central and peripheral melanocortin system, comprising of five receptors and their endogenous ligands, is responsible for a wide array of physiological functions such as skin pigmentation, sexual function and development, and inflammation. A growing body of both clinical and pre-clinical research is demonstrating the relevance of this system in metabolic health. Disruption of hypothalamic melanocortin signalling is the most common cause of monogenic obesity in humans. Setmelanotide, an FDA-approved analogue of alpha-melanocyte stimulating hormone (α-MSH) that functions by restoring central melanocortin signalling, has proven to be a potent pharmacological tool in the treatment of syndromic obesity. As the first effective therapy targeting the melanocortin system to treat metabolic disorders, its approval has sparked research to further harness the links between these melanocortin receptors and metabolic processes. Here, we outline the structure of the central and peripheral melanocortin system, discuss its critical role in the regulation of food intake, and review promising targets that may hold potential to treat metabolic disorders in humans.

Sex, race, and BMI in clinical trials of medications for obesity over the past three decades: a systematic review.

Medications for obesity have been studied in various populations over the past three decades. We aimed to quantify the baseline demographic characteristics of BMI, sex, age, and race in randomised clinical trials (RCTs) across three decades to establish whether the population studied is representative of the global population affected by the disease. Clinical trials of 12 medications for obesity (ie, orlistat, naltrexone-bupropion, topiramate-phentermine, liraglutide, semaglutide, lorcaserin, sibutramine, rimonabant, taranabant, tirzepatide, retatrutide, and orforglipron) published from Jan 20, 1999, to Nov 12, 2023, were assessed through a systematic review for methodological quality and baseline demographic characteristics. 246 RCTs were included, involving 139 566 participants with or without type 2 diabetes. Most trials over-recruited White, female participants aged 40 years or older with class 1 (30·0-34·9 kg/m2) and class 2 (35·0-39·9 kg/m2) obesity; older participants, those with class 3 (≥40·0 kg/m2) obesity, non-White participants, and male participants were under-recruited. Our systematic review suggests that future trials need to recruit traditionally under-represented populations to allow for accurate measures of efficacy of medications for obesity, enabling more informed decisions by clinicians. It is also hoped that these data will help to refine trial recruitment strategies to ensure that future studies are relevant to the population affected by obesity.

Real world use of tirzepatide in the treatment of type 2 diabetes in an Arab population.

AIM: Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) dual receptor agonist (RA) that reduces glycated haemoglobin (HbA1c) and weight in patients with type 2 diabetes. We assessed the effectiveness of tirzepatide in real-world use in an Arab population. METHODS: Review of clinical data from a specialist outpatient diabetes centre; study time points and outcome measures were pre-specified. RESULTS: Tirzepatide was initiated in 8945 patients between 24 October 2022 and 31 December 2023. Of these, 3686 individuals reached 40 weeks of follow-up. At initiation, the mean ± SD age was 54.1 ± 11.5 years, body mass index 34.6 ± 6.0 kg/m2 and HbA1c 7.3 ± 1.5% (56 ± 17 mmol/mol); 2296 (62%) were switched to tirzepatide from another GLP-RA and 317 (8.6%) reported previous bariatric surgery. The maximum dose dispensed was ≥12.5 mg/week in 1087, 7.5-10.0 mg/week in 1688 and 2.5-5.0 mg/week in 911. The mean 40-week reduction in HbA1c was 0.6 ± 1.2% (8 ± 13 mmol/mol) and the reduction in weight was 4.5 ± 6.9 kg (4.8 ± 7.3%). GLP-RA-naïve patients experienced a significantly greater reduction in HbA1c [1.0 ± 1.3% (11 ± 14 mmol/mol) versus 0.5 ± 1.2% (6 ± 13 mmol/mol), p < .0001] and weight (7.2 ± 8.6 vs. 4.2 ± 6.6 kg, p < .0001) compared with previously exposed individuals. Post-metabolic bariatric surgery patients lost significantly more weight (7.8 ± 9.4 vs. 4.5 ± 7.0 kg, p < .0001). Improvements in blood pressure, lipid profile, and liver transaminases were noted at 40 weeks. Tirzepatide was well tolerated, with 288 (7.8%) of patients discontinuing treatment because of adverse effects, predominantly gastrointestinal. CONCLUSION: In real-world use, tirzepatide significantly reduced HbA1c levels and weight and was well tolerated. Previous GLP-RA use was associated with significantly lesser HbA1c and weight reduction, and previous metabolic bariatric surgery was associated with greater weight loss.

Effectiveness of integrating a pragmatic pathway for prescribing liraglutide 3.0 mg in weight management services (STRIVE study): a multicentre, open-label, parallel-group, randomized controlled trial.

Background: An effective prescribing pathway for liraglutide 3 mg, an approved obesity pharmacotherapy, may improve treatment access. This trial compared a targeted prescribing pathway for liraglutide 3 mg with multiple stopping rules in specialist weight management services (SWMS) to standard SWMS care. Methods: This phase four, two-year, multicentre, open-label, parallel-group, real-world randomized clinical trial (ClinicalTrials.gov: NCT03036800) enrolled adults with BMI ≥35 kg/m2 plus prediabetes, type 2 diabetes, hypertension or sleep apnoea from five SWMS in Ireland and UK. Participants were randomly allocated (2:1, stratified by centre and BMI) to SWMS care plus a targeted prescribing pathway for once daily subcutaneous liraglutide 3 mg (intervention) with stopping rules at 16 (≥5% weight loss, WL), 32 (≥10% WL) and 52 weeks (≥15% WL) or to SWMS care alone (control) through an online randomization service. The primary outcome was WL ≥15% at 52 weeks, assessed by complete cases analysis. All randomized participants were included in safety analysis. Findings: From November 28, 2017 to February 28, 2020, 434 participants were screened, and 392 randomized (260 intervention; 132 control), while 294 (201 intervention; 93 control) included in the 52 weeks complete case analysis. More intervention than control participants achieved WL ≥15% at 52 weeks [51/201 (25.4%) vs 6/93 (6.5%); odds ratio 5.18; 95% CI 2.09, 12.88; p < 0.0001]. More adverse events occurred in the intervention (238/260, 91.5%; two deaths) than control (89/132, 67.4%; no deaths) group. Interpretation: A targeted prescribing pathway for liraglutide 3 mg helps more people achieve ≥15% WL at 52 weeks than standard care alone. Funding: Novo Nordisk A/S.

Bariatric surgery for spontaneous ovulation in women living with polycystic ovary syndrome: the BAMBINI multicentre, open-label, randomised controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Obesity exacerbates the reproductive complications of PCOS; however, the management of obesity in women with PCOS remains a large unmet clinical need. Observational studies have indicated that bariatric surgery could improve the rates of ovulatory cycles and prospects of fertility; however, the efficacy of surgery on ovulation rates has not yet been compared with behavioural modifications and medical therapy in a randomised trial. The aim of this study was to compare the safety and efficacy of bariatric surgery versus medical care on ovulation rates in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. METHODS: In this multicentre, open-label, randomised controlled trial, 80 women older than 18 years, with a diagnosis of PCOS based on the 2018 international evidence-based guidelines for assessing and managing PCOS, and a BMI of 35 kg/m2 or higher, were recruited from two specialist obesity management centres and via social media. Participants were randomly assigned at a 1:1 ratio to either vertical sleeve gastrectomy or behavioural interventions and medical therapy using a computer-generated random sequence (PLAN procedure in SAS) by an independent researcher not involved with any other aspect of the clinical trial. The median age of the entire cohort was 31 years and 79% of participants were White. The primary outcome was the number of biochemically confirmed ovulatory events over 52 weeks, and was assessed using weekly serum progesterone measurements. The primary endpoint included the intention-to-treat population and safety analyses were per-protocol population. This study is registered with the ISRCTN registry (ISRCTN16668711). FINDINGS: Participants were recruited from Feb 20, 2020 to Feb 1, 2021. 40 participants were assigned to each group and there were seven dropouts in the medical group and ten dropouts in the surgical group. The median number of ovulations was 6 (IQR 3·5-10·0) in the surgical group and 2 (0·0-4·0) in the medical group. Women in the surgical group had 2.5 times more spontaneous ovulations compared with the medical group (incidence rate ratio 2·5 [95% CI 1·5-4·2], p<0·0007). There were more complications in the surgical group than the medical group, although without long-term sequelae. There were 24 (66·7%) adverse events in the surgical group and 12 (30·0%) in the medical group. There were no treatment-related deaths. INTERPRETATION: Bariatric surgery was more effective than medical care for the induction of spontaneous ovulation in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. Bariatric surgery could, therefore, enhance the prospects of spontaneous fertility in this group of women. FUNDING: The Jon Moulton Charity Trust.

Weight loss with GLP-1 analogues in preparation for transplantation.

This case describes a woman in her 20s with a 6-month history of progressive exertional dyspnoea and cough. Examination revealed hypoxia on room air, sinus tachycardia, finger clubbing and bibasal inspiratory crackles. Inflammatory markers were mildly elevated and empirical antimicrobial therapy was commenced. A multidisciplinary discussion consensus diagnosis of acute interstitial pneumonitis was made based on the findings of high-resolution CT of the chest, macrophage predominant bronchoalveolar lavage cell differential and surgical lung biopsy. There was clinical and radiological deterioration despite glucocorticoids and antifibrotic therapy. A body mass index of 37.5 kg/m2 precluded her from lung transplant assessment and consideration. Following consultation with the weight management service, she was commenced on glucagon-like peptide 1 (GLP-1) analogue therapy. She had a remarkable response within 6 months, was listed for lung transplantation, and within 18 months of her initial presentation, a double lung transplantation was performed.

"Treated as second class citizens" - the lived experience of obesity-related stigma: an IMI2 SOPHIA study.

PURPOSE: Obesity-related stigma impacts on and shapes the physical and psychosocial wellbeing of individuals living with obesity. Often absent from the literature in the field is the voice(s) of those living with obesity capturing the nuances of the lived experiences of obesity-related stigma. METHODS: This study adopted a qualitative approach encompassing individual (n = 15) and photovoice method (n = 12), with a purposeful sample of patients accessing treatment for obesity within the healthcare setting during 2021. Analysis was undertaken using thematic analysis. RESULTS: Key themes developed from the analysis related to experiencing obesity-related stigma as exposure to external judgement, societal exclusion and felt environmental stigmatization. Exposure to external judgement was described as judgemental comments resulting in hypervigilance to societal judgement. Participants reported how being overlooked and ignored by others had various negative effects and compounded obesity-related stigma through societal exclusion. Public spaces lacking suitable equipment further made obesity-related stigma visible through felt environmental stigmatization when pursuing hobbies and in everyday life. CONCLUSIONS: Obesity-related stigma had a profoundly negative impact on participants in this study, particularly in shaping social interaction, limiting life experiences and impacting psychosocial wellbeing.

Changes in food preferences and ingestive behaviors after glucagon-like peptide-1 analog treatment: techniques and opportunities.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) analogs are approved for the treatment of obesity in adults and adolescents. Reports have emerged that the weight loss effect of these medications may be related to changes in food preferences and ingestive behaviors following the treatment. Understanding the mechanisms which impact ingestive behavior could expand opportunities to develop more refined and personalized treatment options for obesity. METHODS: Recent studies investigating the relationship between GLP-1 analogs and ingestive behaviors were retrieved from PubMed using the search terms: "obesity," "food preference," "taste," "ingestive behavior," "weight loss medication," "anti-obesity medication," "GLP-1 analog," "tirzepatide," "liraglutide," "semaglutide." Measurement tools were studied to compare variables used to assess food intake behavior. The main outcomes from each study were analyzed to evaluate the current standing and future directions of appetitive, ingestive, and consummatory behaviors and their association with GLP-1 analogs. RESULTS: Thus far, studies have primarily explored the weight loss phase and report decreased short-term appetite and food intake upon treatment. However, research during the weight maintenance phase and objective measurements of food intake are notably sparse. Additionally, verbal reports have been primarily used to examine food intake, which can be susceptible to subjectivity. CONCLUSIONS: Elucidating the relationship between GLP-1 analogs and ingestive behavior could reveal additional parameters which contribute to their anti-obesity effects. To better understand these mechanisms, it is imperative to consider objective measurements of food intake in future studies. Several measurement tools have been adapted to measure variables of food behavior in humans, and each must be carefully considered with their strengths and limitations to develop optimal investigations.

Genetic Evidence of Causal Relation Between Intestinal Glucose Absorption and Early Postprandial Glucose Response: A Mendelian Randomization Study.

The postprandial glucose response is an independent risk factor for type 2 diabetes. Observationally, early glucose response after an oral glucose challenge has been linked to intestinal glucose absorption, largely influenced by the expression of sodium-glucose cotransporter 1 (SGLT1). This study uses Mendelian randomization (MR) to estimate the causal effect of intestinal SGLT1 expression on early glucose response. Involving 1,547 subjects with class II/III obesity from the Atlas Biologique de l'Obésité Sévère cohort, the study uses SGLT1 genotyping, oral glucose tolerance tests, and jejunal biopsies to measure SGLT1 expression. A loss-of-function SGLT1 haplotype serves as the instrumental variable, with intestinal SGLT1 expression as the exposure and the change in 30-min postload glycemia from fasting glycemia (Δ30 glucose) as the outcome. Results show that 12.8% of the 1,342 genotyped patients carried the SGLT1 loss-of-function haplotype, associated with a mean Δ30 glucose reduction of -0.41 mmol/L and a significant decrease in intestinal SGLT1 expression. The observational study links a 1-SD decrease in SGLT1 expression to a Δ30 glucose reduction of -0.097 mmol/L. MR analysis parallels these findings, associating a statistically significant reduction in genetically instrumented intestinal SGLT1 expression with a Δ30 glucose decrease of -0.353. In conclusion, the MR analysis provides genetic evidence that reducing intestinal SGLT1 expression causally lowers early postload glucose response. This finding has a potential translational impact on managing early glucose response to prevent or treat type 2 diabetes.