Liraglutide 3 mg on weight, body composition, and hormonal and metabolic parameters in women with obesity and polycystic ovary syndrome: a randomized placebo-controlled-phase 3 study.

OBJECTIVE: To study the efficacy and safety of the GLP-1 analog liraglutide 3 mg (LIRA 3 mg) vs. placebo (PL) for reduction of body weight (BW) and hyperandrogenism in women with obesity and polycystic ovary syndrome (PCOS). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Hospital-based outpatient endocrine and metabolic center. PATIENT(S): Women diagnosed with PCOS (NIH criteria) were randomly assigned to LIRA 3 mg (n = 55) or PL (n = 27) once daily for 32 weeks with lifestyle intervention. INTERVENTION(S): Study visits at baseline and 32 weeks included BW and body composition by dual-energy x-ray absorptiometry. Oral glucose tolerance tests were done with sex steroids, free androgen index (FAI), and lipids measured in the fasting sample. MAIN OUTCOME MEASURE(S): The primary end points were changes in BW and FAI. Safety was assessed in all patients who received at least one dose of the study drug. RESULT(S): Change in BW from baseline to week 32 was -5.7% (±0.75) with LIRA 3 mg vs. -1.4% (±1.09) with PL. At week 32, more participants on LIRA 3 mg than on PL achieved at least 5% weight reductions (25 of 44 vs. 5 of 23). Free androgen index significantly reduced with LIRA 3 mg compared with the PL where the mean FAI slightly increased. Gastrointestinal events, which were mostly mild to moderate, were reported in 58.2% of the LIRA 3 mg-subjects and 18.5% of PL subjects. CONCLUSION(S): LIRA 3 mg once daily appears superior to PL in reducing BW and androgenicity and improving cardiometabolic parameters in women with PCOS and obesity. CLINICAL TRIAL REGISTRATION NUMBER: NCT03480022.

Exenatide, Dapagliflozin, or Phentermine/Topiramate Differentially Affect Metabolic Profiles in Polycystic Ovary Syndrome.

CONTEXT: Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors reduce weight and improve insulin sensitivity via different mechanisms. OBJECTIVE: The efficacy of once-weekly exenatide (EQW) and dapagliflozin (DAPA) alone and coadministered (EQW/DAPA), DAPA/extended-release (ER) metformin (DAPA/MET), and phentermine topiramate extended release (PHEN/TPM) on metabolic parameters, body composition, and sex hormones were examined in obese women with PCOS. METHODS: Nondiabetic women (n = 119; aged 18-45 years) with a body mass index (BMI) greater than 30 and less than 45 and polycystic ovary syndrome (National Institutes of Health criteria) were randomly assigned in a single-blinded fashion to EQW (2 mg weekly); DAPA (10 mg daily), EQW/DAPA (2 mg weekly/10 mg daily), DAPA (10 mg)/MET (2000 mg XR daily), or PHEN (7.5 mg)/TPM (46 mg ER daily) treatment for 24 weeks. Study visits at baseline and 24 weeks included weight, blood pressure (BP), waist (WC) measures, and body composition evaluated by dual-energy x-ray absorptiometry (DXA). Oral glucose tolerance tests were conducted to assess glycemia and mean blood glucose (MBG), and compute insulin sensitivity (SI) and secretion (IS) measures. Sex steroids, free androgen index (FAI), and lipid profiles were measured in the fasting sample. RESULTS: EQW/DAPA and PHEN/TPM resulted in the most loss of weight and total body fat by DXA, and WC. Despite equivalent reductions in BMI and WC with PHEN/TPM, only EQW/DAPA and EQW resulted in significant improvements in MBG, SI, and IS. Reductions in fasting glucose, testosterone, FAI, and BP were seen with all drugs. CONCLUSION: Dual therapy with EQW/DAPA was superior to either alone, DAPA/MET and PHEN/TPM in terms of clinical and metabolic benefits in this patient population.

An assay to measure angiogenesis in human fat tissue.

BACKGROUND: Inhibition of angiogenesis reverses rodent obesity. A validated assay in human fat tissue is needed to study the role of angiogenesis in human obesity. METHODS: Human fat tissue fragments from surgery were placed in 96-well plates, embedded in fibrin thrombin clot and overlaid with cell culture media containing 20% fetal bovine serum. After 15 days, the clots were examined by histology and electron microscopy. The effect of taxol, cobalt chloride and a heparin-steroid combination was tested in the fat tissue assay and compared to the validated human placental vein angiogenesis model (HPVAM). RESULTS: Blood vessels initiated growth and elongated from the fat tissue fragments over 15 days. Presence of blood vessels was confirmed with histology and electron microscopy. Taxol at 10(-6) and 10(-7) M completely inhibited angiogenesis, while Taxol 10(-8) and 10(-9) M and the heparin-steroid partially inhibited angiogenesis. The response to taxol and heparin-steroid was similar to that of the HPVAM, a validated angiogenesis assay. Cobalt chloride, a stimulator of vascular endothelial growth factor (VEGF) stimulated angiogenesis initiation at 10(-9) M in fat tissue and the HPVAM, but at 10(-10) M blood vessel growth was stimulated only in the fat assay. CONCLUSION: This angiogenesis assay based on human fat tissue uses three-dimensionally intact human tissue. The vessels are derived from quiescient vessels within the fat. These properties allow the angiogenic switch to be evaluated in an in vitro setting. The angiogenic response of fat tissue is not identical to placental tissue. This assay allows exploration of angiogenesis in fat tissue.

Evaluation of continuous infusion of 0.5% bupivacaine by elastomeric pump for postoperative pain management after open inguinal hernia repair.

BACKGROUND: Postoperative pain management and narcotic usage after inguinal hernia repair is an important concern for anesthesiologists and surgeons. Regional anesthesia incisional infiltration techniques may reduce the need for systemic medications. STUDY DESIGN: Double-blind study of 52 patients undergoing open hernia repair with the Prolene Hernia System prospectively randomized to receive either 0.5% bupivacaine or saline continuously for 48 hours at 2 mL/hour through use of an elastomeric continuous infusion pump (ONQ Pain Relief System). Outcomes measured over the 120 hours postoperatively were: narcotic use, Visual Analogue Scale pain scores, site inflammation (visual inspection), and side effects. Comparisons between the groups were made by applying the Mann-Whitney rank sum test and analysis of variance with treatment as a fixed effect in the model. RESULTS: In the bupivacaine group, 24% (versus 4% in the placebo group) required no narcotics (p < 0.05). Daily and total narcotic usages for all 5 study days were significantly less (p < 0.05) in the bupivacaine group. There were no reports of complications at the catheter-insertion site or surgical-wound site. CONCLUSIONS: Demonstrable benefits include reduction of narcotic usage and pain with no apparent increase in the risk of infection or complication. Continuous infusion of 0.5% bupivacaine at 2 mL/h through the ONQ pump is a safe and effective adjunct in postoperative pain management for open inguinal hernia repair. This represents a viable and possibly superior option for prolonged pain management, minimizing use of narcotics in patients undergoing this procedure.

Short-term pilot study of the effect of sleeve gastrectomy on food preference.

The effect of vertical sleeve gastrectomy (VSG) on food preference has not been examined in humans, but VSG decreases preference for fat and calorically dense foods in rodents. A validated Food Preference Questionnaire (FPQ) assessed food preference changes before and 6 weeks after VSG in humans. The FPQ was completed before and 43 ± 19 days (Mean ± SD) after VSG. Fifteen subjects (14 females) completed the study. Hedonic ratings decreased for foods high in fat and sugar (p = 0.002) and high in fat and complex carbohydrate (p = 0.007). Fat preference (p = 0.048) decreased, VSG reduced preference for calorically dense foods high in fat, sugar, and complex carbohydrate, and these changes may contribute to the weight loss with VSG.

Early resolution of type 2 diabetes seen after Roux-en-Y gastric bypass and vertical sleeve gastrectomy.

BACKGROUND: Type 2 diabetes (T2D) accounts for the majority of diagnosed cases of diabetes in adults in the United States. Many of these individuals are also morbidly obese and choose to undergo bariatric surgery to lose weight and gain glycemic control. The Roux-en-Y gastric bypass (RYGB) has been shown to resolve diabetes before substantial weight loss occurs. Several studies suggest that the vertical sleeve gastrectomy (VSG), a newer bariatric operation, may result in comparable weight loss and rapid diabetes control. METHODS: We conducted a retrospective chart review of 262 patients diagnosed with diabetes who underwent either the RYGB or the VSG between 2002 and 2010. Medication usage before and after surgery was recorded. Patients who discontinued all medications postoperatively were considered "resolved" of T2D, and those who reduced the number of medications were considered as "showing improvement" in their T2D. Peri- and postoperative complications were also recorded for each operation. RESULTS: At 8 weeks postoperatively, follow-up data were available for 38 RYGB patients and 71 VSG patients. Approximately 79% of RYGB patients and 83% of VSG patients remained off their diabetes medication. VSG patients experienced a significantly lower incidence of major and minor complications both peri- and postoperatively compared with RYGB patients. CONCLUSIONS: Both operations appear to equally resolve T2D in an obese, adult population; however, the incidence of both major and minor complications is much lower in the VSG patient group. Therefore, the VSG should also be considered as a treatment option for obese individuals with T2D.

Racial differences in weight loss, payment method, and complications following Roux-en-Y gastric bypass and sleeve gastrectomy.

OBJECTIVES: Obesity affects approximately one-third of the US adult population. Although more black adults are considered to be obese compared to white adults, black adults are less likely to undergo bariatric surgery for weight loss. Black adults typically lose less weight and are more prone to adverse events following bariatric surgery than white adults. The objectives of this study were to compare weight loss, payment methods, and early postoperative complications between black and white adults. DESIGN: A retrospective chart review of 420 Roux-en-Y gastric bypass (RYGB) patients and 454 sleeve gastrectomy (SG) patients (all female) was conducted. A mixed-model analysis was used to assess statistical significance of differences in weight loss between surgeries and races. A Chi-square test was used to assess racial differences in payment method (insurance or private pay) and postoperative complications by operation. Statistical significance was set as P > 0.05. RESULTS: RYGB patients lost significantly more weight at 26, 52, 78, and 104 weeks postoperatively compared to SG patients. White females (WF) lost significantly more weight than black females (BF) at 26, 52, 78, and 104 weeks postoperatively. WF experienced more minor and major complications in the perioperative period than BF, but BF experienced more minor and overall complications in the postoperative period than WF. A greater percentage of black patients had insurance coverage compared to white patients for both surgeries. CONCLUSION: WF appear to lose more weight than BF regardless of surgery, but both races experience surgical complications. Black patients may be less likely to undergo bariatric surgery without insurance coverage.

International Sleeve Gastrectomy Expert Panel Consensus Statement: best practice guidelines based on experience of >12,000 cases.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an emerging surgical approach, but 1 that has seen a surge in popularity because of its perceived technical simplicity, feasibility, and good outcomes. An international expert panel was convened in Coral Gables, Florida on March 25 and 26, 2011, with the purpose of providing best practice guidelines through consensus regarding the performance of LSG. The panel comprised 24 centers and represented 11 countries, spanning all major regions of the world and all 6 populated continents, with a collective experience of >12,000 cases. It was thought prudent to hold an expert consensus meeting of some of the surgeons across the globe who have performed the largest volume of cases to discuss and provide consensus on the indications, contraindications, and procedural aspects of LSG. The panel undertook this consensus effort to help the surgical community improve the efficacy, lower the complication rates, and move toward adoption of standardized techniques and measures. The meeting took place at on-site meeting facilities, Biltmore Hotel, Coral Gables, Florida. METHODS: Expert panelists were invited to participate according to their publications, knowledge and experience, and identification as surgeons who had performed >500 cases. The topics for consensus encompassed patient selection, contraindications, surgical technique, and the prevention and management of complications. The responses were calculated and defined as achieving consensus (≥70% agreement) or no consensus (<70% agreement). RESULTS: Full consensus was obtained for the essential aspects of the indications and contraindications, surgical technique, management, and prevention of complications. Consensus was achieved for 69 key questions. CONCLUSION: The present consensus report represents the best practice guidelines for the performance of LSG, with recommendations in the 3 aforementioned areas. This report and its findings support a first effort toward the standardization of techniques and adoption of working recommendations formulated according to expert experience.

Laparoscopic sleeve gastrectomy, 529 cases without a leak: short-term results and technical considerations.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is gaining acceptance among bariatric surgeons as a viable option for treating morbidly obese patients. We describe results of a single surgeon's experience with LSG in a community practice revealing a low complication rate and describing the surgical technique. METHODS: LSG was performed in 529 consecutive patients from December 2006 to March 2010. A technique is described where all operations were performed with attention to avoiding strictures at the incisura angularis and stapling close to the esophagus at the angle of His. No operations performed used buttressing material or over-sewing of the staple line. A retrospective chart review and e-mail survey was conducted to determine the occurrence of complications and weight loss. RESULTS: Follow-up data was collected on 490 of the 529 (92.6%) patients at 6 weeks. A total complication rate of 3.2% and a 1.7% 30-day readmission rate were observed. No leaks occurred in any of the 529 patients, and one death (0.19%) was observed. The most common complications were nausea and vomiting with dehydration and venous thrombosis. The percentages of excess weight loss were 42.36, 65.92, 66.11, and 64.42 with a follow-up of 71%, 68%, 63%, and 49% at 6 months, 1 year, 2, and 3 years, respectively. CONCLUSION: The LSG can be performed in a community practice with a low complication rate. Surgeons performing LSG should strive to minimize the risk of creating strictures at the incisura angularis and stapling near the esophagus at the angle of His.

Safety of the Ullorex oral intragastric balloon for the treatment of obesity.

BACKGROUND: Intragastric balloons have been used for weight loss with varying success. Widespread use of intragastric balloons has been limited because balloons must be placed in, and removed from, the stomach endoscopically. Development of a balloon that does not require endoscopy suggests that obesity treatment with intragastric balloons is feasible. The purpose of this study was to test the Ullorex oral intragastric balloon (OIB) in a sample of human participants. METHODS: The Ullorex OIB is a large capsule that is injected with citric acid and swallowed. After 4 minutes, the balloon inflates to 300 cm(3). Stomach acid degrades a plug on the balloon over 25-30 days, when the balloon deflates and passes in feces. The Ullorex OIB was tested in 12 humans (two participants received placebo capsules). Body weight was monitored before and after balloon placement, and test meals quantified food intake among 6 of the 12 participants, all of whom received one balloon. RESULTS: A single significant adverse event occurred. The one participant randomized to receive three balloons developed nausea and vomiting, requiring intravenous fluids, which was likely influenced by noncompliance (eating solid foods after balloon placement). Participants who received balloons had a significant mean weight loss over 2 weeks, amounting to 1.5 kg (p < 0.05). A marginally significant food intake reduction from baseline to week 1 was found (149 kcal, 24.4%) (p = 0.055). CONCLUSIONS: The Ullorex OIB was successfully utilized in this study, with one serious adverse event that was likely influenced by noncompliance. Body weight and food intake data suggest that the Ullorex OIB be tested further as a possible treatment for obesity.