Achieve Weight Loss Research Articles

Weight Changes Are Linked to Adipose Tissue Genes in Overweight Women with Polycystic Ovary Syndrome

Women with polycystic ovary syndrome (PCOS) have varying difficulties in achieving weight loss by lifestyle intervention, which may depend on adipose tissue metabolism. The objective was to study baseline subcutaneous adipose tissue gene expression as a prediction of weight loss by lifestyle intervention in obese/overweight women with PCOS. This is a secondary analysis of a randomized controlled trial where women with PCOS, aged 18–40 and body mass index (BMI) ≥ 27 were initially randomized to either a 4-month behavioral modification program or minimal intervention according to standard care. Baseline subcutaneous adipose tissue gene expression was related to weight change after the lifestyle intervention. A total of 55 obese/overweight women provided subcutaneous adipose samples at study entry. Weight loss was significant after behavioral modification (−2.2%, p = 0.0014), while there was no significant weight loss in the control group (−1.1%, p = 0.12). In microarray analysis of adipose samples, expression of 40 genes differed significantly between subgroups of those with the greatest weight loss or weight gain. 10 genes were involved in metabolic pathways including glutathione metabolism, gluconeogenesis, and pyruvate metabolism. Results were confirmed by real-time polymerase chain reaction (RT-PCR) in all 55 subjects. Expressions of GSTM5, ANLN, and H3C2 correlated with weight change (R = −0.41, p = 0.002; R = −0.31, p = 0.023 and R = −0.32, p = 0.016, respectively). GSTM5, involved in glutathione metabolism, was the strongest predictor of weight loss, and together with baseline waist-hip ratio (WHR) explained 31% of the variation in body weight change. This study shows that baseline subcutaneous adipose tissue genes play a role for body weight outcome in response to lifestyle intervention in overweight/obese women with PCOS.

The Association between a Recorded Diagnosis of Obesity and Clinically Significant Weight Loss in the Primary Care Setting: A Nationwide Registry.

Overweight and obesity (OW/OB) are underdiagnosed. The primary aim was to assess whether a diagnosis of OW/OB recorded by a primary care physician (PCP) is associated with clinically significant weight loss, compared to a missed diagnosis. The secondary aim was to investigate the association between OW/OB diagnosis and patient attendance at dietary consultations. This retrospective, observational cohort study was conducted using a nationwide healthcare database. The study included a random sample of 200 000 adults with BMI ≥ 25 kg/m2, recorded on a primary care visit, between 2014-2020. Patients with prior diagnosis of OW/OB or obesity-related complications were excluded. The independent variable was OW/OB diagnosis recorded by the PCP immediately after BMI measurement. The outcome variable was ≥5% weight loss at a second weight measurement within 9-15 months. Multivariate regression analysis was applied. Of the 200 00 people with OW/OB, 36 033 (18.0%) had a diagnosis of OW/OB, and 37 368 (18.7%) had a second body weight measurement, of which 7 635 (20.4%) lost ≥5% of their baseline body weight. The prescription rate of anti-obesity medication was 1.2% and did not differ between patients who achieved weight loss and those who did not. Those with a recorded diagnosis were 2.6 times more likely to visit a dietitian (OR 2.57, 95%CI 2.56-2.64) and 2.5 times more likely to achieve weight loss (OR 2.53, 95%CI 2.46-2.60). After adjusting for multiple confounders, including attendance at dietary consultation, people who received OW/OB diagnosis were 32% more likely to achieve weight loss (OR 1.32 95% CI 1.28-1.36, p<0.001) compared to people with missed diagnosis. Recording a diagnosis of obesity among relatively healthy people is associated with clinically significant weight loss at 1 year follow up, independent of attendance at dietary consultation. Early obesity diagnosis is a significant opportunity to promote weight loss in the primary care setting and may affect weight trajectory.

GLP-1 receptor agonists are a transformative prehabilitation tool for weight loss in obese patients undergoing elective hernia repair.

Obesity is an independent risk factor for complications after abdominal hernia repair. Glucagon-like-peptide-1 (GLP-1) receptor agonists are gaining popularity as pharmacologic weight loss adjuncts and may help patients reach weight loss goals for surgery. We examine our early experience utilizing GLP-1 agonists versus lifestyle modifications alone to achieve weight loss in patients before elective hernia repair. This single-center, retrospective review identified obese patients who underwent elective hernia repair from 2014 to 2023. Patients were asked to achieve a BMI ≤ 33kg/m2 before surgery. Patients who lost weight with GLP-1 therapy in addition to lifestyle changes were compared to a control cohort that achieved similar preoperative weight loss without GLP-1 therapy. Primary outcome was mean time from GLP-1 agonist initiation and initial surgery clinic visit to surgery. Secondary outcomes were 30-day morbidity, mortality, and reoperation rates, and hernia recurrence. Forty-six patients with ventral/incisional, flank, umbilical, parastomal, inguinal, and hiatal hernias were identified (GLP-1 N = 24, control N = 22). 81.8% (N = 18) of controls had a ventral/incisional hernia, compared to 45.8% (N = 11) of GLP-1 patients (p = 0.03). Mean BMI at GLP-1 agonist initiation was similar to mean BMI at initial clinic visit for controls (38.1 ± 4.9 vs 38.2 ± 2.7kg/m2, p = 0.66). Preoperative mean percentage total weight loss (14.9 ± 7.5 vs 12.4 ± 6.9kg, p = 0.39) and mean BMI reduction (6.0 ± 3.8 vs 4.9 ± 2.3kg/m2, p = 0.43) were similar between groups. The mean time from GLP-1 agonist initiation to surgery was significantly shorter than initial clinic visit to surgery for controls (6.3 ± 4.0 vs 14.7 ± 17.6months, p = 0.03). There was no statistically significant difference in time from initial clinic visit to surgery between groups (7.6 ± 4.4 vs 14.7 ± 17.6months, p = 0.06). There was no significant difference in 30-day morbidity between groups (8.3 vs 27.3%, p = 0.13). GLP-1 agonists accelerate preoperative weight loss for obese hernia patients without negatively impacting postoperative outcomes.

6488 Factors associated with the response to SGLT2 inhibitors and GLP-1 Receptor Agonists in Veterans with Type 2 Diabetes

Abstract Disclosure: S. Hashmi: None. K. Samson: None. G. Arora: None. S. Azad: None. D. Awad: None. C.V. Desouza: None. Background: SGLT2 inhibitors and GLP1 agonists are recommended as first line pharmacological therapy (along with metformin) for type 2 DM, particularly in patients with CKD, CVD, or HF. Despite their effectiveness, there is limited evidence available to predict which patient subsets will respond favorably to SGLT2 inhibitors or GLP1 agonist. Purpose of study: To determine if baseline characteristics can predict response to therapy and to compare the differences in characteristics between SGLT2 inhibitor and GLP1 agonist groups. Methodology: Retrospective study of veterans ages 19-89 yr with T2DM initiated on treatment from Jan 1, 2015, to Dec 31, 2022, with either SGLT2 inhibitor or GLP 1 agonist for at least 6 months. The cohort comprised 866 patients, of which 544 individuals met the inclusion criteria (332 in the GLP-1 agonist group and 212 in the SGLT2 inhibitor group). Baseline characteristics assessed included age, sex, race, comorbidities, weight, BMI, HbA1c, eGFR, BP and lipids. Treatment response thresholds were defined as an HbA1c reduction of more than 0.5 percentage points and more than 3% of pretreatment weight loss, evaluated 6-12 months after initiating treatment. A complete response was defined as both treatment thresholds being met. Statistical analysis involved Chi-Square tests and independent samples t-test between variables of interest. Logistic regression was conducted with the dichotomous complete response outcome, for variables with bivariate p-values less than 0.10, in addition to variables preselected for inclusion based on the clinical relevance. Results: Three variables were statistically significant in the final logistic regression with complete response outcome. Patients on GLP1 had an increased adjusted odds of having a complete outcome (AOR: 2.45 (95% CI: 1.45, 4.15) relative to patients on SGLT2. In addition, older patients (AOR: 1.34 (95% CI: 1.02, 1.74)) and patients with a higher baseline HbA1c (AOR: 1.18 (95% CI: 1.02, 1.36)) had increased adjusted odds of having a complete response relative to patients 10 years younger and patients with an A1c 1 unit lower, respectively. 72.6% of patients on GLP1 agonists achieved the A1c response goal, in contrast to 48.6% on SGLT2 inhibitors (p < 0.001). Also, 47.6 % of individuals achieved weight loss goals on GLP1 agonist as compared to 41 % on SGLT2 inhibitor. A greater proportion of females (66.7%) achieved the A1c reduction goal compared to males (45.9%) on SGLT2 inhibitors (p = 0.04). Conclusion: Individuals receiving GLP-1 agonists had a twofold increased odds of achieving A1c reduction and weight loss goals after a 6-12 month treatment period compared to those prescribed SGLT2 inhibitors. Older patients and patients with higher baseline A1c levels had greater odds of reaching A1c and weight loss threshold whereas other baseline variables were not significantly associated with the outcome. Presentation: 6/3/2024

Which GLP1 receptor agonist approved for weight loss is the most effective at achieving weight loss?

Which GLP1 receptor agonist approved for weight loss is the most effective at achieving weight loss?

Metabolic and bariatric surgery outcomes in adolescents: a single center's seven-year update.

Metabolic and bariatric surgery (MBS) is gaining traction as a treatment option for adolescents with severe obesity. Since our weight center last published results in 2014, trends have shown increasingly diverse patient populations undergoing MBS and a shift from laparoscopic Roux-en-Y gastric bypass (LRYGB) to sleeve gastrectomy (LSG). We assessed outcomes including follow-up, weight loss, comorbidity resolution, and complications among our recent adolescent and young adult MBS patients. This is a retrospective cohort analysis of patients under 21years of age with severe obesity who underwent MBS at a single institution between 2014 and 2020. Data on demographics, comorbidities, body mass index (BMI), percent of total body weight loss (%TBWL) at various timepoints, and subsequent complications were collected via chart review. Regression examined associations between preoperative factors, follow-up, and %TBWL. There were 79 patients of whom 73% were female; overall, 53% were White, 24% Hispanic, and 15% non-Hispanic Black. The majority (80%) of patients underwent LSG. Three-fourths of patients had follow-up data beyond 1year, and half beyond 3years. The median %TBWL of LSG patients was 23% at a median follow-up of 3.0years, and LRYGB patients 28% at 2.4years. No preoperative factors were associated with follow-up or final %TBWL, but 6-month %TBWL predicted final %TBWL. Preoperatively, 73% of patients had at least one weight-related comorbidity, and 57% had documented improvements in at least one after surgery. There were three 30-day readmissions and no mortalities. This study, which is an update to a previous series from our center, reflects recent national trends with nearly half non-White patients and predominance of LSG over LRYGB. It adds to a growing body of evidence indicating that MBS is a safe and effective method of achieving weight loss and comorbidity resolution in adolescents with severe obesity.

How much more effective is semaglutide in achieving weight loss than other glucagon-like peptide-1 receptor agonists?

How much more effective is semaglutide in achieving weight loss than other glucagon-like peptide-1 receptor agonists?

Safety and efficacy of sleeve gastrectomy in non-diabetic individuals with class I vs. class II obesity: a matched controlled experiment from Tehran Obesity Treatment Study (TOTS).

This study aimed to evaluate the 3-year outcomes of sleeve gastrectomy in non-diabetic individuals with class I obesity. A total of 78 participants with class I obesity and 78 participants with class II obesity, matched in terms of age, sex (93.6% female), and the rates of dyslipidemia and hypertension, were included in this prospective cohort study. Follow-up data, including metabolic features, body composition, nutritional characteristics, and surgery complications, were gathered at the baseline and 6, 12, 24, and 36 months post-bariatric surgery. Micronutrient deficiencies and comorbidities (hypertension and dyslipidemia) were evaluated in both groups using conditional logistic regression analysis, and Clavien-Dindo classification was used to compare surgical complications. Baseline characteristics of the participants in both groups were similar (n = 78, mean age: 36.4 ± 8.5). The two groups were also comparable in terms of weight loss, cardiovascular risk factors, and remission of obesity-related comorbidities 3 years following sleeve gastrectomy. Overall values of Δ total weight loss (TWL)%, Δ excess weight loss (EWL)%, and β (95% CI) were - 1.86 (1.19), and - 2.56 (4.5) with a P value of 0.118 and 0.568, respectively. The occurrence of surgical complications and undesirable outcomes were also similar between the two study groups. Bariatric surgery is an effective and safe method to achieve weight loss and alleviate cardiovascular risk factors and obesity-related comorbidities in non-diabetic individuals with class I and class II obesity.

Gut microbiome shifts in adolescents after sleeve gastrectomy with increased oral-associated taxa and pro-inflammatory potential.

Bariatric surgery is highly effective in achieving weight loss in children and adolescents with severe obesity, however the underlying mechanisms are incompletely understood, and gut microbiome changes are unknown. 1) To comprehensively examine gut microbiome and metabolome changes after laparoscopic vertical sleeve gastrectomy (VSG) in adolescents and 2) to assess whether the microbiome/metabolome changes observed with VSG influence phenotype using germ-free murine models. 1) A longitudinal observational study in adolescents undergoing VSG with serial stool samples undergoing shotgun metagenomic microbiome sequencing and metabolomics (polar metabolites, bile acids and short chain fatty acids) and 2) a human-to-mouse fecal transplant study. We show adolescents exhibit significant gut microbiome and metabolome shifts several months after VSG, with increased alpha diversity and notably with enrichment of oral-associated taxa. To assess causality of the microbiome/metabolome changes in phenotype, pre-VSG and post-VSG stool was transplanted into germ-free mice. Post-VSG stool was not associated with any beneficial outcomes such as adiposity reduction compared pre-VSG stool. However, post-VSG stool exhibited an inflammatory phenotype with increased intestinal Th17 and decreased regulatory T cells. Concomitantly, we found elevated fecal calprotectin and an enrichment of proinflammatory pathways in a subset of adolescents post-VSG. We show that in some adolescents, microbiome changes post-VSG may have inflammatory potential, which may be of importance considering the increased incidence of inflammatory bowel disease post-VSG.

Comparable improvement and resolution of obesity-related comorbidities in endoscopic sleeve gastroplasty vs laparoscopic sleeve gastrectomy: single-center study.

Despite excellent surgical outcomes, a minority of qualified patients undergo weight loss surgery. Endoscopic Sleeve Gastroplasty (ESG), an incisionless procedure, has proven to be effective in achieving weight loss and comorbidity improvement. We aim to compare outcomes of ESG to those of Laparoscopic Sleeve Gastrectomy (LSG). A retrospective review of a prospective database of patients who underwent ESG and LSG at NorthShore University HealthSystem from 2016 to 2023 was completed. Demographic and outcome data were analyzed. Pre- and post-surgical data were compared using chi-square and two-sample t tests. Improvement or resolution of obesity-related comorbidities were also assessed. A total of 212 LSG and 68 ESG patients were reviewed. ESG patients were older (47 ± 10 vs. 43 ± 12, p = 0.006) and less obese (BMI 37.0 ± 5.5 vs. 45.8 ± 0.4, p < 0.001) than LSG patients. Median length of stay after ESG was 0days and after LSG 1day (p < 0.001). Severe adverse events were seen less frequent after ESG (1.47%, vs 3.77%). LSG achieved more significant %TBWL at 6 months (25.2 ± 8.9 vs 14.9 ± 7.4), 1 year (27.5 ± 10.8 vs 14.1 ± 9.8), and 2 years (25.7 ± 10.8 vs 10.5 ± 8.8, all p < 0.001) after surgery when compared to ESG. LSG achieved significantly greater %EWL compared to ESG at 6 months (57.0 ± 20.7 vs 50.4 ± 29.2, p = 0.137), 1 year (61.4 ± 24.6 vs 46.5 ± 34.0, p = 0.026), and 2 years postoperatively (59.7 ± 25.5 vs 32.6 ± 28.2, p = 0.001). There were no statistically significant differences in rates of improvement or resolution of diabetes, obstructive sleep apnea, hyperlipidemia, or hypertension. ESG is an effective procedure for weight loss and comorbidity resolution. Obesity-related comorbidities are comparably improved and resolved following ESG vs LSG. Although the weight loss in LSG is significantly higher, patients can expect a shorter hospital length of stay and a lower rate of complications after ESG. ESG continues to show promise for long-term weight loss and improvement in health.

Lead-in calorie restriction enhances the weight-lowering efficacy of incretin hormone-based pharmacotherapies in mice

ObjectivesThe potential benefits of combining lifestyle changes with weight loss pharmacotherapies for obesity treatment are underexplored. Building on recent clinical observations, this study aimed to determine whether “lead-in” calorie restriction before administering clinically approved weight loss medications enhances the maximum achievable weight loss in preclinical models. MethodsDiet-induced obese mice (DIO) were exposed to 7 or 14 days of calorie restriction before initiating treatment with semaglutide (a glucagon-like peptide-1 receptor (GLP-1R) agonist), tirzepatide (a GLP-1R/glucose insulinotropic peptide receptor (GIPR) co-agonist), or setmelanotide (a melanocortin-4 receptor (MC4R) agonist). Follow-up assessments using indirect calorimetry determined the contributions of energy intake and expenditure linked to consecutive exposure to dieting followed by pharmacotherapy. ResultsCalorie restriction prior to treatment with semaglutide or tirzepatide enhanced the weight loss magnitude of both incretin-based therapies in DIO mice, reflected by a reduction in fat mass and linked to reduced energy intake and a less pronounced adaptive drop in energy expenditure. These benefits were not observed with the MC4R agonist, setmelanotide. ConclusionsOur findings provide compelling evidence that calorie restriction prior to incretin-based therapy enhances the achievable extent of weight loss, as reflected in a weight loss plateau at a lower level compared to that of treatment without prior calorie reduction. This work suggests that more intensive lifestyle interventions should be considered prior to pharmacological treatment, encouraging further exploration and discussion of the current standard of care.

The role of impulsivity and binge eating in outpatients with overweight or obesity: an EEG temporal discounting study

BackgroundBinge eating (BE) is associated with a range of cognitive control deficits related to impulsivity, including lower response inhibition, preference for immediate gratification, and maladaptive decision-making. The aim was to investigate whether impulsivity and BE may interact with the decision process and underlying brain activity in outpatients with overweight or obesity who are starting a treatment to achieve weight loss.MethodsA sample of 26 treatment-seeking outpatients with overweight or obesity was evaluated for impulsivity, BE, and temporal discounting rates. Impulsivity was measured with the Barratt Impulsiveness Scale (BIS-11), according to which two groups were composed: high BIS and low BIS; BE was assessed with the eating disorders module of the Structured Clinical Interview for DSM5—Research Version, according to which two groups were composed: with (BE group) or without BE (NBE group). Changes in subjective value of rewards were measured with the Temporal Discounting Task (TDt) where participants had to choice between sooner but smaller vs. later but larger monetary rewards. These choices were made in two differently delayed conditions (“Now” and “Not-now”). Brain rhythms were recorded through high-density electroencephalogram (hd-EEG) during the TDt.ResultsPatients with BE reported more impulsive tendencies and perceived sooner rewards as more gratifying when both options were delayed (Not-now condition, p = 0.02). The reward choice in the TDt was accompanied by a general EEG alpha band desynchronization in parietal areas observed without differences between experimental conditions and patients groups. No effects were observed within the Now condition or in the other EEG bands.ConclusionsThe tendency to favor immediate rewards may constitute an obstacle to adhering to treatment plans and achieving weight loss goals for outpatients with overweight or obesity. Clinicians are therefore encouraged to include psychological factors, such as impulsivity and dysfunctional eating behaviors, when designing weight loss programs. By addressing these psychological aspects, clinicians can better support patients in overcoming barriers to adherence and achieving sustainable weight loss.Trial registrationThis study was approved by the Ethics Committee of the Department of Psychological, Health, and Territorial Sciences of the University G. d’Annunzio of Chieti-Pescara (Prot. n. 254 of 03/14/2017).

Medical and Surgical Weight Loss as a Pathway to Renal Transplant Listing.

Severe obesity is a barrier to listing for kidney transplantation due to concern for poor outcomes. This study aims to compare bariatric surgery with medical weight loss as a means of achieving weight loss and subsequent listing for renal transplant. We hypothesize that bariatric surgery will induce greater frequency of listing for transplant within 18 months of study initiation. We performed a randomized study of metabolic bariatric surgery (MBS) vs medical weight loss (MM) in patients on dialysis with a body mass index (BMI) of 40-55kg/m2. The primary outcome was suitability for renal transplant within 18 months of initiating treatment. Secondary outcomes included weight loss, mortality, and complications. Twenty patients enrolled, only 9 (5 MBS, 4MM) received treatment. Treated groups did not differ in age, gender, or race (P ≥ .44). There was no statistically significant difference in the primary endpoint: 2 MBS (40%) and 1MM (25%) listed for transplant ≤18 months (P = 1.00). With additional time, 100% MBS and 25% MM patients achieved listing status (P = .048); 100% of MBS and 0MM received kidney transplants to date (P = .008). Weight, weight loss, and BMI trajectories differed between the groups (P ≤ .002). One death from COVID-19 occurred in the MM group, and 1 MBS patient had a myocardial infarction 3.75 years after baseline evaluation. These results suggest MBS is superior to MM in achieving weight loss prior to listing for kidney transplantation. Larger studies are needed to ensure the safety profile is acceptable in patients with ESRD undergoing bariatric surgery.

Preventing diabetes complications.

The key aim of diabetes management is to prevent complications, which are a major cause of morbidity and mortality. At an individual level, people with diabetes are less likely than they were several decades ago to experience classical macrovascular and microvascular complications as a result of improvements in modifiable cardiovascular risk factors and preventive healthcare. However, a significant burden of diabetes complications persists at a population level because of the increasing incidence of diabetes, as well as longer lifetime exposure to diabetes because of younger diagnosis and increased life expectancy. Trials have shown that the most effective strategy for preventing complications of diabetes is a multifactorial approach focussing simultaneously on the management of diet, exercise, glucose levels, blood pressure and lipids. In addition to the cornerstone strategies of addressing diet, exercise and lifestyle measures, the introduction of newer glucose-lowering agents, including sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 agonists, have brought about a paradigm shift in preventing the onset and progression of complications of type 2 diabetes, particularly cardiovascular and renal disease. The improvement in rates of classical complications of diabetes over time has been accompanied by a growing awareness of non-traditional complications, including non-alcoholic fatty liver disease. These emerging complications may not respond to a glycaemic-centred approach alone and highlight the importance of foundational strategies centred on lifestyle measures and supported by pharmaceutical therapy to achieve weight loss and reduce metabolic risk in patients living with diabetes.

Impacts of dietary animal and plant protein on weight and glycemic control in health, obesity and type 2 diabetes: friend or foe?

It is well established that high-protein diets (i.e. ~25-30% of energy intake from protein) provide benefits for achieving weight loss, and subsequent weight maintenance, in individuals with obesity, and improve glycemic control in type 2 diabetes (T2D). These effects may be attributable to the superior satiating property of protein, at least in part, through stimulation of both gastrointestinal (GI) mechanisms by protein, involving GI hormone release and slowing of gastric emptying, as well as post-absorptive mechanisms facilitated by circulating amino acids. In contrast, there is evidence that the beneficial effects of greater protein intake on body weight and glycemia may only be sustained for 6-12 months. While both suboptimal dietary compliance and metabolic adaptation, as well as substantial limitations in the design of longer-term studies are all likely to contribute to this contradiction, the source of dietary protein (i.e. animal vs. plant) has received inappropriately little attention. This issue has been highlighted by outcomes of recent epidemiological studies indicating that long-term consumption of animal-based protein may have adverse effects in relation to the development of obesity and T2D, while plant-based protein showed either protective or neutral effects. This review examines information relating to the effects of dietary protein on appetite, energy intake and postprandial glycemia, and the relevant GI functions, as reported in acute, intermediate- and long-term studies in humans. We also evaluate knowledge relating to the relevance of the dietary protein source, specifically animal or plant, to the prevention, and management, of obesity and T2D.

Efficacy and safety of tirzepatide versus placebo in overweight or obeseadults without diabetes: a systematic review and meta-analysis of randomized controlled trials.

Tirzepatide was approved to treat type 2 diabetes and obesity, but its efficacy and safety in patients without diabetes has not beeninvestigated. This meta-analysis aimed to evaluate the efficacy and safety of tirzepatide compared to placebo in overweight or obesepatients without diabetes. PubMed, Embase and Cochrane were searched on January 18, 2024. Randomized controlled trials (RCTs) that used tirzepatide in overweight or obeseadults without diabetes were included. Efficacy outcomes included the proportion of participants achieving weight loss targets, changes in body weight (%), body mass index (BMI), waist circumference (WC), and blood pressure (BP). Safety outcomes were commonly reported adverse events. Standardized mean differences (SMD) or odds ratios (OR) with 95% confidence intervals (CIs) were used for continuous and dichotomous outcomes, respectively. Three RCTs with 3901 participants were included. Tirzepatide was associated with increased proportion of participants achieving weight loss targets, reduced body weight (SMD -1.61, 95% CI -2.20 to -1.02), BMI (SMD -2.13, 95% CI -3.08 to -1.18), WC (SMD -0.91, 95% CI -1.14 to -0.69), and BP versus placebo. However, the risk of adverse events such as nausea (OR 4.26, 95% CI 2.60 to 3.81), vomiting (OR 8.35, 95% CI 5.19 to 13.45), and diarrhea (OR 3.57, 95% CI 2.80 to 4.57) was significantly higher for tirzepatide versus placebo. Tirzepatide significantly reduced weight and improved metabolic markers among overweight or obesewithout diabetes. However, increased adverse events highlights the need for benefits versus risks assessment before initiation and continuous monitoring.

Personalized Nutrition Therapy without Weight Loss Counseling Produces Weight Loss in Individuals with Prediabetes Who Are Overweight/Obese: A Randomized Controlled Trial.

Obesity stands out as a primary risk factor for diabetes. Attaining healthy weight loss, especially reducing body fat, is important in managing prediabetes and preventing progression to full diabetes and its co-morbidities. This study examined the effects of personalized nutrition therapy (PNT) combined with continuous glucose monitoring (CGM) on body weight and composition in individuals with prediabetes. A total of 30 individuals with prediabetes who were overweight or obese were assigned randomly to either the treatment, observed CGM data plus PNT, or the control group which was blinded to their blood glucose results throughout the study. Both groups were provided with dietary recommendations for calorie intake and macronutrient distribution, coupled with personalized goal setting for glucose control and healthy eating, without any specific emphasis on weight reduction or changes in physical activity. Regular visits were scheduled every 10 days to perform measurements and replace CGMs. Data were analyzed using General Linear Model with repeated measures. Over the 30-day follow-up period, both groups experienced significant reductions in weight and fat mass. The treatment group exhibited two-fold greater reductions in both weight and fat mass, a significant decrease in carbohydrate intake, and a significant increase in time spent on physical activitycompared to the control group. In addition, compliance was notably higher in the treatment group. These findings indicate that overweight or obese individuals with prediabetes can achieve weight loss and improved body composition through personalized education for glucose control, without exclusively emphasizing weight loss as the primary objective. Additionally, the real-time feedback provided by CGM enhances these improvements.

The Impact of Longer Biliopancreatic Limb Length on Weight Loss and Comorbidity Improvement at 5 Years After Primary Roux-en-Y Gastric Bypass Surgery: A Population-Based Matched Cohort Study

IntroductionDifferent limb lengths are used in Roux-en-Y gastric bypass (RYGB) surgery, as there is no consensus which limb length strategy has the best outcomes. The biliopancreatic limb (BPL) is thought to play an important role in achieving weight loss and associated comorbidity resolution. The objective of this study was to assess the impact of a longer BPL on weight loss and comorbidity improvement at 5 years after primary RYGB.MethodsAll patients aged ≥ 18 years undergoing primary RYGB between 2014–2017 with registered follow-up 5 years after surgery were included. Long BPL was defined as BPL ≥ 100 cm and short BPL as BPL < 100 cm. The primary outcome was achieving at least 25% total weight loss (TWL) at 5 years. Secondary outcomes included absolute %TWL and improvement of comorbidities. A propensity score matched logistic and linear regression was used to estimate the difference in outcomes between patients with long and short BPL.ResultsAt 5 years, long BPL had higher odds to achieve ≥ 25% TWL (odds ratio (OR) 1.19, 95% confidence interval (CI) [1.01 – 1.41]) and was associated with 1.26% higher absolute TWL (β = 1.26, 95% CI [0.53 – 1.99]). Furthermore, long BPL was more likely to result in improved diabetes mellitus (OR = 2.17, 95% CI [1.31 – 3.60]) and hypertension (OR = 1.45, 95% CI [1.06 – 1.99]).ConclusionPatients undergoing RYGB with longer BPL achieved higher weight loss and were more likely to achieve improvement of comorbidities at 5 years.Graphical

Longitudinal gut microbial signals are associated with weight loss: insights from a digital therapeutics program.

The gut microbiome's influence on weight management has gained significant interest for its potential to support better obesity therapeutics. Patient stratification leading to personalized nutritional intervention has shown benefits over one-size-fit-all diets. However, the efficacy and impact on the gut's microbiome of personalizing weight loss diets based on individual factors remains under-investigated. This study assessed the impact of Digbi Health's personalized dietary and lifestyle program on weight loss and the gut microbiome end-points in 103 individuals. Participants' weight loss patterns and gut microbiome profiles were analyzed from baseline to follow-up samples. Specific microbial genera, functional pathways, and communities associated with BMI changes and the program's effectiveness were identified. 80% of participants achieved weight loss. Analysis of the gut microbiome identified genera and functional pathways associated with a reduction in BMI, including Akkermansia, Christensenella, Oscillospiraceae, Alistipes, and Sutterella, short-chain fatty acid production, and degradation of simple sugars like arabinose, sucrose, and melibiose. Network analysis identified a microbiome community associated with BMI, which includes multiple taxa known for associations with BMI and obesity. The personalized dietary and lifestyle program positively impacted the gut microbiome and demonstrated significant associations between gut microbial changes and weight loss. These findings support the use of the gut microbiome as an endpoint in weight loss interventions, highlighting potential microbiome biomarkers for further research.

Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity

Although tirzepatide and semaglutide were shown to reduce weight in randomized clinical trials, data from head-to-head comparisons in populations with overweight or obesity are not yet available. To compare on-treatment weight loss and rates of gastrointestinal adverse events (AEs) among adults with overweight or obesity receiving tirzepatide or semaglutide labeled for type 2 diabetes (T2D) in a clinical setting. In this cohort study, adults with overweight or obesity receiving semaglutide or tirzepatide between May 2022 and September 2023 were identified using electronic health record (EHR) data linked to dispensing information from a collective of US health care systems. On-treatment weight outcomes through November 3, 2023, were assessed. Adults with overweight or obesity and regular care in the year before initiation, no prior glucagon-like peptide 1 receptor agonist receptor agonist use, a prescription within 60 days prior to initiation, and an available baseline weight were identified. The analysis was completed on April 3, 2024. Tirzepatide or semaglutide in formulations labeled for T2D, on or off label. On-treatment weight change in a propensity score-matched population, assessed as hazard of achieving 5% or greater, 10% or greater, and 15% or greater weight loss, and percentage change in weight at 3, 6, and 12 months. Hazards of gastrointestinal AEs were compared. Among 41 222 adults meeting the study criteria (semaglutide, 32 029; tirzepatide, 9193), 18 386 remained after propensity score matching. The mean (SD) age was 52.0 (12.9) years, 12 970 were female (70.5%), 14 182 were white (77.1%), 2171 Black (11.8%), 354 Asian (1.9%), 1679 were of other or unknown race, and 9563 (52.0%) had T2D. The mean (SD) baseline weight was 110 (25.8) kg. Follow-up was ended by discontinuation for 5140 patients (55.9%) receiving tirzepatide and 4823 (52.5%) receiving semaglutide. Patients receiving tirzepatide were significantly more likely to achieve weight loss (≥5%; hazard ratio [HR], 1.76, 95% CI, 1.68, 1.84; ≥10%; HR, 2.54; 95% CI, 2.37, 2.73; and ≥15%; HR, 3.24; 95% CI, 2.91, 3.61). On-treatment changes in weight were larger for patients receiving tirzepatide at 3 months (difference, -2.4%; 95% CI -2.5% to -2.2%), 6 months (difference, -4.3%; 95% CI, -4.7% to -4.0%), and 12 months (difference, -6.9%; 95% CI, -7.9% to -5.8%). Rates of gastrointestinal AEs were similar between groups. In this population of adults with overweight or obesity, use of tirzepatide was associated with significantly greater weight loss than semaglutide. Future study is needed to understand differences in other important outcomes.