Tirzepatide Once Weekly for the Treatment of Obesity.

BACKGROUND: Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known. METHODS: In this phase 3 double-blind, randomized, controlled trial, we assigned 2539 adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period. Coprimary end points were the percentage change in weight from baseline and a weight reduction of 5% or more. The treatment-regimen estimand assessed effects regardless of treatment discontinuation in the intention-to-treat population. RESULTS: At baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher. The mean percentage change in weight at week 72 was -15.0% (95% confidence interval [CI], -15.9 to -14.2) with 5-mg weekly doses of tirzepatide, -19.5% (95% CI, -20.4 to -18.5) with 10-mg doses, and -20.9% (95% CI, -21.8 to -19.9) with 15-mg doses and -3.1% (95% CI, -4.3 to -1.9) with placebo (P<0.001 for all comparisons with placebo). The percentage of participants who had weight reduction of 5% or more was 85% (95% CI, 82 to 89), 89% (95% CI, 86 to 92), and 91% (95% CI, 88 to 94) with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 35% (95% CI, 30 to 39) with placebo; 50% (95% CI, 46 to 54) and 57% (95% CI, 53 to 61) of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% (95% CI, 1 to 5) in the placebo group (P<0.001 for all comparisons with placebo). Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively. CONCLUSIONS: In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. (Supported by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).

Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.

Importance: The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. Objective: To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction. Design, Setting, and Participants: This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes. Interventions: Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. Main Outcomes and Measures: The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period. Results: Participants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo. Conclusions and Relevance: In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. Trial Registration: ClinicalTrials.gov Identifier: NCT04660643.

New insights into the treatment of obesity.

Obesity is a chronic, progressive and relapsing disease with a rising global prevalence associated with increased morbidity and mortality and reduced quality of life. Treatment of obesity requires a comprehensive medical approach that includes behavioural interventions, pharmacotherapy and bariatric surgery. The degree of weight loss with all approaches is highly heterogeneous, and long-term weight maintenance remains challenging. For years, antiobesity medications have been limited in number, often delivering meagre efficacy and raising numerous safety concerns. Therefore, there is a need for the development of highly efficacious and safe new agents. Recent insights into the complex pathophysiology of obesity have increased our understanding of intervenable targets for pharmacotherapies to treat obesity and improve weight-related cardiometabolic complications, namely, type 2 diabetes, hyperlipidaemia and hypertension. As a result, novel potent therapies have emerged, such as semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) recently approved for the treatment of obesity. Semaglutide 2.4 mg once weekly significantly reduces body weight by approximately 15%, with simultaneous improvement in cardiometabolic risk factors and physical functioning in people with obesity. Tirzepatide, the first dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RA, has recently demonstrated that body weight reduction exceeding 20% in people with obesity and coupled with improved cardiometabolic measures is feasible. Thus, these novel agents promise to narrow the gap between the weight-loss effects of behaviour interventions, previous pharmacotherapies, and bariatric surgery. In this narrative review, we highlight established and emerging therapeutic treatments for long-term obesity management and position them in a framework according to their weight loss effects.

Five-Year Outcomes of Endoscopic Sleeve Gastroplasty for the Treatment of Obesity.

BACKGROUND AND AIMS: The growing burden of obesity as a chronic disease necessitates a multifaceted approach to management. There has been an increase in the number of available endoscopic therapies for weight management with endoscopic sleeve gastroplasty (ESG) proving to be one of the best options. The long-term efficacy of ESG for management of obesity is not known. This study sought to assess the long-term safety and efficacy of ESG for treatment of obesity. METHODS: This was a prospective cohort study. Participants underwent ESG in a single academic center, and were prospectively enrolled. All procedures were performed by the same therapeutic endoscopist. Patients with a body mass index of >30 kg/m2 (or >27 with comorbidities), who underwent ESG from August 2013 to August 2019 for treatment of obesity were enrolled. Patients were followed for up to 5 years after their procedure. The primary outcome was weight loss at 5 years after the procedure (% total body weight loss, TBWL) RESULTS: 216 patients (68% female) with a mean age of 46±13 years, and mean BMI of 39±6 kg/m2 underwent ESG. Out of 216 patients, 203, 96, and 68 patients were eligible for a 1-, 3-, and 5-year follow up, with complete follow-up rates of 70%, 71%, and 82%, respectively. At 5 years, mean TBWL was 15.9% (95% CI, 11.7-20.5, p < .001) and 90 and 61% of patients maintained 5 and 10% TBWL, respectively. There was an overall rate of 1.3% moderate adverse events (AEs), without any severe or fatal AEs. CONCLUSIONS: Our results suggest that ESG is safe and effective for treatment of obesity, with durable long-term results for at least up to 5 years after the procedure. This procedure should be considered as a reliable option for treatment of obesity.

Outpatient metformin use is associated with reduced severity of COVID-19 disease in adults with overweight or obesity.

Observational studies suggest outpatient metformin use is associated with reduced mortality from coronavirus disease-2019 (COVID-19). Metformin is known to decrease interleukin-6 and tumor-necrosis factor-α, which appear to contribute to morbidity in COVID-19. We sought to understand whether outpatient metformin use was associated with reduced odds of severe COVID-19 disease in a large US healthcare data set. Retrospective cohort analysis of electronic health record (EHR) data that was pooled across multiple EHR systems from 12 hospitals and 60 primary care clinics in the Midwest between March 4, 2020 and December 4, 2020. Inclusion criteria: data for body mass index (BMI) > 25 kg/m2 and a positive SARS-CoV-2 polymerase chain reaction test; age ≥ 30 and ≤85 years. Exclusion criteria: patient opt-out of research. Metformin is the exposure of interest, and death, admission, and intensive care unit admission are the outcomes of interest. Metformin was associated with a decrease in mortality from COVID-19, OR 0.32 (0.15, 0.66; p = .002), and in the propensity-matched cohorts, OR 0.38 (0.16, 0.91; p = .030). Metformin was associated with a nonsignificant decrease in hospital admission for COVID-19 in the overall cohort, OR 0.78 (0.58-1.04, p = .087). Among the subgroup with a hemoglobin HbA1c available (n = 1193), the adjusted odds of hospitalization (including adjustment for HbA1c) for metformin users was OR 0.75 (0.53-1.06, p = .105). Outpatient metformin use was associated with lower mortality and a trend towards decreased admission for COVID-19. Given metformin's low cost, established safety, and the mounting evidence of reduced severity of COVID-19 disease, metformin should be prospectively assessed for outpatient treatment of COVID-19.

Improvement in insulin resistance and estimated hepatic steatosis and fibrosis after endoscopic sleeve gastroplasty.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and is closely associated with obesity and insulin resistance (IR). Weight loss is the best treatment for NAFLD. Endoscopic sleeve gastroplasty (ESG) is a promising endoscopic procedure for treatment of obesity. Our aim is to evaluate the change in IR and estimated hepatic steatosis and fibrosis after ESG. METHODS: One hundred eighteen patients with obesity and NAFLD underwent ESG and were followed for 2 years. Weight loss was evaluated as % total body weight loss. IR was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). The previously validated hepatic steatosis index and NAFLD fibrosis score were used to estimate hepatic steatosis and risk of fibrosis. RESULTS: Patients' mean body mass index was 40 ± 7 kg/m2 at baseline. Eighty-four percent of patients completed 2 years of follow-up. At 2 years, the mean total body weight loss was 15.5% (95% confidence interval, 13.3%-17.8%). Patients' HOMA-IR improved significantly from 6.7 ± 11 to 3.0 ± 1.6 after only 1 week from ESG (P = .019) with continued improvement up to 2 years (P = .03). Patients' hepatic steatosis index score improved significantly, decreasing by 4 points per year (P for trend, <.001). Patients' NAFLD fibrosis score improved significantly, decreasing by 0.3 point per year (P for trend, .034). Twenty-four patients (20%) improved their risk of hepatic fibrosis from F3-F4 or indeterminate to F0-F2, whereas only 1 patient (1%) experienced an increase in the estimated risk of fibrosis (P = .02). CONCLUSIONS: Our results suggest a significant and sustained improvement in estimated hepatic steatosis and fibrosis after ESG in patients with NAFLD. Importantly, we showed an early and weight-independent improvement in insulin resistance, which lasted for 2 years after the procedure.

Changes in weight control behaviors and hedonic hunger in a commercial weight management program adapted for individuals with type 2 diabetes.

BACKGROUND: A WW (formerly Weight Watchers) program adapted for persons with type 2 diabetes mellitus (T2DM) previously was found to be more effective than standard care (SC) intervention for weight loss, improved glycemic control, and weight- and diabetes-related quality of life measures. With data from the same national trial, this study examined whether WW adapted for persons with T2DM also increased engagement in weight control behaviors and decreased hedonic hunger, each of which could contribute to improved diabetes management. INTERVENTION AND METHODS: Individuals with T2DM (n = 563) and overweight or obesity participated in a 12-month, 16-site, randomized trial of WW with diabetes counseling or SC. Hierarchical linear modeling (HLM) evaluated whether 12-month changes in weight control behaviors (Eating Behavior Inventory; EBI) and hedonic hunger (Power of Food Scale; PFS) differed by treatment condition. If a significant treatment effect was found, 12-month changes in EBI/PFS were regressed on 12-month changes in HbA1c and percent weight loss to explore potential treatment differences in these associations. RESULTS: EBI scores increased significantly over the 12-months (p < 0.001), with greater improvements in WW than SC (p < 0.001). PFS decreased significantly in the 12-months (p < 0.001), with no differences between treatment groups (p = 0.15). HLM analyses that followed up on the significant treatment effect for 12-month change in EBI revealed no significant differences by treatment condition for the relationship between change in EBI scores and change in HbA1c (p = 0.14) or percent weight loss (p = 0.32). Across all participants, 12-month improvements in EBI and PFS were related to improved HbA1c (r = 0.22; -0.13, respectively) and greater percent weight loss (r = 0.41; -0.18, respectively) (ps < 0.01). CONCLUSIONS: WW with diabetes counseling produced greater engagement in weight control behaviors in those with T2DM than did SC. Across both groups, improved weight control behaviors and hedonic hunger were related to improved glycemic control and weight loss.

Effect of an Online Weight Management Program Integrated With Population Health Management on Weight Change: A Randomized Clinical Trial.

Importance: Online programs may help with weight loss but have not been widely implemented in routine primary care. Objective: To compare the effectiveness of a combined intervention, including an online weight management program plus population health management, with the online program only and with usual care. Design, Setting, and Participants: Cluster randomized trial with enrollment from July 19, 2016, through August 10, 2017, at 15 primary care practices in the US. Eligible participants had a scheduled primary care visit and were aged 20 to 70 years, had a body mass index between 27 and less than 40, and had a diagnosis of hypertension or type 2 diabetes. Follow-up ended on May 8, 2019. Interventions: Participants in the usual care group (n = 326) were mailed general information about weight management. Participants in the online program only group (n = 216) and the combined intervention group (n = 298) were registered for the online program. The participants in the combined intervention group also received weight-related population health management, which included additional support from nonclinical staff who monitored their progress in the online program and conducted periodic outreach. Main Outcomes and Measures: The primary outcome was weight change at 12 months based on measured weights recorded in the electronic health record. Weight change at 18 months was a secondary outcome. Results: Among the 840 participants who enrolled (mean age, 59.3 years [SD, 8.6 years]; 60% female; 76.8% White), 732 (87.1%) had a recorded weight at 12 months and the missing weights for the remaining participants were imputed. There was a significant difference in weight change at 12 months by group with a mean weight change of -1.2 kg (95% CI, -2.1 to -0.3 kg) in the usual care group, -1.9 kg (95% CI, -2.6 to -1.1 kg) in the online program only group, and -3.1 kg (95% CI, -3.7 to -2.5 kg) in the combined intervention group (P < .001). The difference in weight change between the combined intervention group and the usual care group was -1.9 kg (97.5% CI, -2.9 to -0.9 kg; P < .001) and the difference between the combined intervention group and the online program only group was -1.2 kg (95% CI, -2.2 to -0.3 kg; P = .01). At 18 months, the mean weight change was -1.9 kg (95% CI, -2.8 to -1.0 kg) in the usual care group, -1.1 kg (95% CI, -2.0 to -0.3 kg) in the online program only group, and -2.8 kg (95% CI, -3.5 to -2.0 kg) in the combined intervention group (P < .001). Conclusions and Relevance: Among primary care patients with overweight or obesity and hypertension or type 2 diabetes, combining population health management with an online program resulted in a small but statistically significant greater weight loss at 12 months compared with usual care or the online program only. Further research is needed to understand the generalizability, scalability, and durability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02656693.

The impact of food order on postprandial glycaemic excursions in prediabetes.

Data suggest that nutrient order during a meal significantly impacts postprandial glucose and insulin excursions in type 2 diabetes, while its effects in prediabetes have not been reported. Fifteen participants with prediabetes consumed the same meal on 3 days in random order: carbohydrate first, followed 10 minutes later by protein and vegetables (CF); protein and vegetables first, followed 10 minutes later by carbohydrate (PVF); or vegetables first followed by protein and carbohydrate (VF). Blood was sampled for glucose and insulin measurements at 0, 30, 60, 90, 120, 150 and 180 minutes. Incremental glucose peaks were similarly attenuated by >40% in the PVF and VF meal conditions compared with CF. The incremental area under the curve for glucose was 38.8% lower following the PVF meal order, compared with CF, and postprandial insulin excursions were significantly lower in the VF meal condition compared with CF. The CF meal pattern showed marked glycaemic variability whereas glucose levels were stable in the PVF and VF meal conditions. Food order presents a novel, simple behavioural strategy to reduce glycaemic excursions in prediabetes.

Practical Use of Pharmacotherapy for Obesity.

Obesity management requires a multidisciplinary approach, as there are many factors that contribute to the development of obesity, as well as the preservation of excess weight once it has been gained. Diet, exercise, and behavior modification are key components of treatment. In addition to lifestyle changes, weight gain secondary to medications is an important modifiable risk factor. Even after appropriate lifestyle modification, and medication adjustments (where possible) to avoid agents that can contribute to weight gain, many patients are still unable to achieve clinically meaningful weight loss. Pharmacotherapy for obesity management can fill an important role for these patients. This article will review medications that can lead to weight gain and potential alternatives, currently approved anti-obesity medications and best practices to individualize the selection process, and the use of testosterone in men with hypogonadism and obesity.

Single Fluid-Filled Intragastric Balloon Safe and Effective for Inducing Weight Loss in a Real-World Population.

BACKGROUND & AIMS: The Orbera intragastric balloon (OIB) is a single fluid-filled intragastric balloon approved for the induction of weight loss and treatment of obesity. However, little is known about the effectiveness and safety of the OIB outside clinical trials, and since approval, the Food and Drug Administration has issued warnings to health care providers about risk of balloon hyperinflation requiring early removal, pancreatitis, and death. We analyzed data on patients who have received the OIB since its approval to determine its safety, effectiveness, and tolerance in real-world clinical settings. METHODS: We performed a postregulatory approval study of the safety and efficacy of the OIB, and factors associated with intolerance and response. We collected data from the Mayo Clinic's database of patient demographics, outcomes of OIB placement (weight loss, weight-related comorbidities), technical aspects of insertion and removal, and adverse events associated with the device and/or procedure, from 8 centers (3 academic, 5 private, 4 surgeons, and 4 gastroenterologists). Our final analysis comprised 321 patients (mean age, 48.1 ± 11.9 y; 80% female; baseline body mass index, 37.6 ± 6.9). Exploratory multivariable linear and logistic regression analyses were performed to identify predictors of success and early balloon removal. Primary effectiveness outcomes were percentage of total body weight lost at 3, 6, and 9 months. Primary and secondary safety outcomes were rates of early balloon removal, periprocedural complications, dehydration episodes requiring intravenous infusion, balloon migration, balloon deflation or hyperinflation, pancreatitis, or other complications. RESULTS: Four patients had contraindications for placement at the time of endoscopy. The balloon was safely removed in all instances with an early removal rate (before 6 months) in 16.7% of patients, at a median of 8 weeks after placement (range, 1-6 mo). Use of selective serotonin or serotonin-norepinephrine re-uptake inhibitors at the time of balloon placement was associated with increased odds of removal before 6 months (odds ratio, 3.92; 95% CI, 1.24-12.41). Total body weight lost at 3 months was 8.5% ± 4.9% (n = 204), at 6 months was 11.8% ± 7.5% (n = 199), and at 9 months was 13.3% ± 10% (n = 47). At 6 months, total body weight losses of 5%, 10%, and 15% were achieved by 88%, 62%, and 31% of patients, respectively. Number of follow-up visits and weight loss at 3 months were associated with increased weight loss at 6 months (ß = 0.5 and 1.2, respectively) (P < .05). Mean levels of cholesterol, triglycerides, low-density lipoprotein, and hemoglobin A1c, as well as systolic and diastolic blood pressure, were significantly improved at 6 months after OIB placement (P < .05). CONCLUSIONS: In an analysis of a database of patients who received endoscopic placement of the OIB, we found it to be safe, effective at inducing weight loss, and to reduce obesity-related comorbidities in a real-world clinical population. Rates of early removal (before 8 weeks) did not differ significantly between clinical trials and the real-world population, but were affected by use of medications.

A single-operator learning curve analysis for the endoscopic sleeve gastroplasty.

BACKGROUND AND AIMS: Endoscopic sleeve gastroplasty (ESG) is a novel, incisionless technique for gastric volume reduction to promote weight loss. Our aim was to describe the learning curve for performing ESG using a prospective case series. METHODS: Using a prospective case series design, we analyzed the first 128 consecutive patients at a tertiary care academic medical center who underwent ESG performed by a single operator from August 2013 to December 2016. Efficiency (refining performance to decrease procedure time) and mastery (absence of outliers) for performing ESG was evaluated by using a penalized basis-spline regression and cumulative sum analysis. RESULTS: Efficiency for ESG was attained after 38 ESGs, with mastery after 55 procedures. At 12 months, the mean percent total body weight loss was 15.8% (standard deviation, 9.47%). A total of 71.7% of patients achieved successful weight loss. When using multiple linear regression analysis, both number of sutures and baseline weight were significantly associated with procedure time. Other patient characteristics, such as age, sex, and race, did not significantly affect procedure time. In addition, number of sutures, baseline weight, and endoscopist achieving efficiency were not correlated with successful weight loss at 12 months. CONCLUSIONS: Mastery of ESG by a single operator is suggested after sufficient endoscopic experience and may help guide widespread clinical adaptability.

White Paper AGA: POWER - Practice Guide on Obesity and Weight Management, Education, and Resources.

The epidemic of obesity continues at alarming rates, with a high burden to our economy and society. The American Gastroenterological Association understands the importance of embracing obesity as a chronic, relapsing disease and supports a multidisciplinary approach to the management of obesity. Because gastrointestinal disorders resulting from obesity are more frequent and often present sooner than type 2 diabetes mellitus and cardiovascular disease, gastroenterologists have an opportunity to address obesity and provide an effective therapy early. Patients who are overweight or obese already fill gastroenterology clinics with gastroesophageal reflux disease and its associated risks of Barrett's esophagus and esophageal cancer, gallstone disease, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, and colon cancer. Obesity is a major modifiable cause of diseases of the digestive tract that frequently goes unaddressed. As internists, specialists in digestive disorders, and endoscopists, gastroenterologists are in a unique position to play an important role in the multidisciplinary treatment of obesity. This American Gastroenterological Association paper was developed with content contribution from Society of American Gastrointestinal and Endoscopic Surgeons, The Obesity Society, Academy of Nutrition and Dietetics, and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, endorsed with input by American Society for Gastrointestinal Endoscopy, American Society for Metabolic and Bariatric Surgery, American Association for the Study of Liver Diseases, and Obesity Medicine Association, and describes POWER: Practice Guide on Obesity and Weight Management, Education and Resources. Its objective is to provide physicians with a comprehensive, multidisciplinary process to guide and personalize innovative obesity care for safe and effective weight management.

Endoscopic Sleeve Gastroplasty Significantly Reduces Body Mass Index and Metabolic Complications in Obese Patients.

BACKGROUND & AIMS: Endoscopic sleeve gastroplasty (ESG) is an incisionless, minimally invasive bariatric procedure that reduces the length and width of the gastric cavity to facilitate weight loss. We performed a prospective study to evaluate the effects of ESG on total body weight loss and obesity-related comorbidities. METHODS: We collected data from 91 consecutive patients (mean age, 43.86 ± 11.26 years; 68% female) undergoing ESG from August 2013 through March 2016. All patients had a body mass index (BMI) greater than 30 kg/m2 and had failed noninvasive weight-loss measures or had a BMI greater than 40 kg/m2 and were not considered as surgical candidates or refused surgery. All procedures were performed with a cap-based flexible endoscopic suturing system to facilitate a triangular pattern of sutures to imbricate the greater curvature of the stomach. Patients were evaluated after 6 months (n = 73), 12 months (n = 53), and 24 months (n = 12) for anthropometric features (BMI, weight, waist circumference, blood pressure) and underwent serologic (hemoglobin A1c), lipid panel, serum triglycerides, and liver function tests. The primary outcomes were total body weight loss at 6, 12, and 24 months. Secondary outcomes were the effects of ESG on metabolic factors (blood pressure, diabetes, hyperlipidemia, steatohepatitis) and safety. RESULTS: The patients' mean BMI before the procedure was 40.7 ± 7.0 kg/m2. Patients had lost 14.4% of their total body weight at 6 months (80% follow-up rate), 17.6% at 12 months (76% follow-up rate), and 20.9% at 24 months (66% follow-up rate) after ESG. At 12 months after ESG, patients had statistically significant reductions in levels of hemoglobin A1c (P = .01), systolic blood pressure (P = .02), waist circumference (P < .001), alanine aminotransferase (P < .001), and serum triglycerides (P = .02). However, there was no significant change in low-density lipoprotein after vs before ESG (P = .79). There was one serious adverse event (1.1%) (perigastric leak) that occurred that was managed non-operatively. CONCLUSIONS: ESG is a minimally invasive and effective endoscopic weight loss intervention. In addition to sustained total body weight loss up to 24 months, ESG reduced markers of hypertension, diabetes, and hypertriglyceridemia.

Percutaneous Gastrostomy Device for the Treatment of Class II and Class III Obesity: Results of a Randomized Controlled Trial.

OBJECTIVES: The AspireAssist System (AspireAssist) is an endoscopic weight loss device that is comprised of an endoscopically placed percutaneous gastrostomy tube and an external device to facilitate drainage of about 30% of the calories consumed in a meal, in conjunction with lifestyle (diet and exercise) counseling. METHODS: In this 52-week clinical trial, 207 participants with a body-mass index (BMI) of 35.0-55.0 kg/m2 were randomly assigned in a 2:1 ratio to treatment with AspireAssist plus Lifestyle Counseling (n=137; mean BMI was 42.2±5.1 kg/m2) or Lifestyle Counseling alone (n=70; mean BMI was 40.9±3.9 kg/m2). The co-primary end points were mean percent excess weight loss and the proportion of participants who achieved at least a 25% excess weight loss. RESULTS: At 52 weeks, participants in the AspireAssist group, on a modified intent-to-treat basis, had lost a mean (±s.d.) of 31.5±26.7% of their excess body weight (12.1±9.6% total body weight), whereas those in the Lifestyle Counseling group had lost a mean of 9.8±15.5% of their excess body weight (3.5±6.0% total body weight) (P<0.001). A total of 58.6% of participants in the AspireAssist group and 15.3% of participants in the Lifestyle Counseling group lost at least 25% of their excess body weight (P<0.001). The most frequently reported adverse events were abdominal pain and discomfort in the perioperative period and peristomal granulation tissue and peristomal irritation in the postoperative period. Serious adverse events were reported in 3.6% of participants in the AspireAssist group. CONCLUSIONS: The AspireAssist System was associated with greater weight loss than Lifestyle Counseling alone.

Pharmacotherapy for Weight Management in the VHA.

Weight management medications (WMM) are underutilized as an adjunct to behavioral and lifestyle interventions. In fiscal years 2014-2015, a total of approximately 2500 veterans-a mere 2% of veterans receiving care from the Veterans Health Administration (VHA)-eligible for a WMM received a prescription for one. A State of the Art Conference on Weight Management workgroup, focused on pharmacotherapy, developed evidence-based recommendations and strategies to foster the appropriate use of WMM in the VHA. The workgroup identified patient, prescriber, and health system barriers to and facilitators for prescribing WMM. Barriers included patient and provider concerns about medication safety and efficacy, limited involvement of primary care, restrictive medication criteria for use (CFU), and skepticism among providers regarding the safety and efficacy of WMM and the perception of obesity as a disease. Potential facilitators for removing barriers included patient and provider education about WMM and the health benefits of weight loss, increased engagement of primary care providers in weight management, relaxation of the CFU, and creation of a system to help patients navigate through weight management treatment options. Several research questions were framed with regard to WMM in general, and specifically to the care of obese veterans. While some of the workgroup's conclusions reflect issues specific to the VHA, many are likely to be applicable to other health organizations.