Mindful eating for weight loss in women with obesity: a randomised controlled trial.

Mindful eating (ME) has been linked to improvement in binge eating disorder, but this approach in obesity management has shown conflicting results. Our aim was to assess the effect of ME associated with moderate energy restriction (MER) on weight loss in women with obesity. Metabolic parameters, dietary assessment, eating behaviour, depression, anxiety and stress were also evaluated. A total of 138 women with obesity were randomly assigned to three intervention groups: ME associated with MER (ME + MER), MER and ME, and they were followed up monthly for 6 months. ME + MER joined seven monthly mindfulness-based intervention group sessions each lasting 90 min and received an individualised food plan with MER (deficit of 2092 kJ/d - 500 kcal/d). MER received an individualised food plan with MER (deficit of 2092 kJ/d - 500 kcal/d), and ME joined seven monthly mindfulness-based intervention group sessions each lasting 90 min. Seventy patients completed the intervention. Weight loss was significant, but no statistically significant difference was found between the groups. There was a greater reduction in uncontrolled eating in the ME group than in the MER group and a greater reduction in emotional eating in the ME group than in both the MER and the ME + MER groups. No statistically significant differences were found in the other variables evaluated between groups. The association between ME with energy restriction did not promote greater weight loss than ME or MER.

Differences in the gut microbiota of women according to ultra-processed food consumption.

BACKGROUND AND AIMS: High consumption of ultra-processed food (UPF) has been associated with increased risk of obesity and other metabolic diseases, and this dietary pattern seems to be responsible for chronic changes in the gut microbiota. The aim of this study was to assess the associations of UPF with the gut microbiota and obesity-associated biometrics in women. METHODS AND RESULTS: This cross-sectional study examined 59 women. The following parameters were evaluated: food consumption using NOVA classification, anthropometric and metabolic parameters, and gut microbiome by next-generation sequencing. The mean age was 28.0 ± 6.6 years. The mean caloric intake was 1624 ± 531 kcal, of which unprocessed or minimally processed food (G1) accounted for 52.4 ± 13.5%, and UPF accounted for 31.4 ± 13.6%. Leptin levels adjusted for fat mass were negatively associated with G1 and positively associated with UPF. We found 15 species in the gut microbiota that correlated with G1 (3 positively and 12 negatively) and 9 species associated with UPF (5 positively and 4 negatively). CONCLUSION: Higher consumption of UPF was directly associated with leptin resistance, and this study suggests that the consumption of UPF or G1 may affect the composition of the gut microbiota.

Safety and efficacy of hydrothermal duodenal mucosal resurfacing in patients with type 2 diabetes: the randomised, double-blind, sham-controlled, multicentre REVITA-2 feasibility trial.

OBJECTIVE: Hydrothermal duodenal mucosal resurfacing (DMR) is a safe, outpatient endoscopic procedure. REVITA-2, a double-blind, superiority randomised controlled trial, investigates safety and efficacy of DMR using the single catheter Revita system (Revita DMR (catheter and system)), on glycaemic control and liver fat content in type 2 diabetes (T2D). DESIGN: Eligible patients (haemoglobin A1c (HbA1c) 59-86 mmol/mol, body mass index≥24 and ≤40 kg/m2, fasting insulin >48.6 pmol/L, ≥1 oral antidiabetic medication) enrolled in Europe and Brazil. Primary endpoints were safety, change from baseline in HbA1c at 24 weeks, and liver MRI proton-density fat fraction (MRI-PDFF) at 12 weeks. RESULTS: Overall mITT (DMR n=56; sham n=52), 24 weeks post DMR, median (IQR) HbA1c change was -10.4 (18.6) mmol/mol in DMR group versus -7.1 (16.4) mmol/mol in sham group (p=0.147). In patients with baseline liver MRI-PDFF >5% (DMR n=48; sham n=43), 12-week post-DMR liver-fat change was -5.4 (5.6)% in DMR group versus -2.9 (6.2)% in sham group (p=0.096). Results from prespecified interaction testing and clinical parameter assessment showed heterogeneity between European (DMR n=39; sham n=37) and Brazilian (DMR n=17; sham n=16) populations (p=0.063); therefore, results were stratified by region. In European mITT, 24 weeks post DMR, median (IQR) HbA1c change was -6.6 mmol/mol (17.5 mmol/mol) versus -3.3 mmol/mol (10.9 mmol/mol) post-sham (p=0.033); 12-week post-DMR liver-fat change was -5.4% (6.1%) versus -2.2% (4.3%) post-sham (p=0.035). Brazilian mITT results trended towards DMR benefit in HbA1c, but not liver fat, in context of a large sham effect. In overall PP, patients with high baseline fasting plasma glucose ((FPG)≥10 mmol/L) had significantly greater reductions in HbA1c post-DMR versus sham (p=0.002). Most adverse events were mild and transient. CONCLUSIONS: DMR is safe and exerts beneficial disease-modifying metabolic effects in T2D with or without non-alcoholic liver disease, particularly in patients with high FPG. TRIAL REGISTRATION NUMBER: NCT02879383.

Non-invasive methods for iron overload evaluation in dysmetabolic patients.

INTRODUCTION: Although hyperferritinemia may reflect the inflammatory status of patients with non-alcoholic fatty liver disease (NAFLD), approximately 33% of hyperferritinemia cases reflect real hepatic iron overload. AIM: To evaluate a non-invasive method for assessing mild iron overload in patients with NAFLD using 3T magnetic resonance imaging (MRI) relaxometry, serum hepcidin, and the expression of ferritin subunits. METHODS: This cross-sectional study assessed patients with biopsy-proven NAFLD. MRI relaxometry was performed using a 3T scanner in all patients, and the results were compared with iron content determined by liver biopsy. Ferritin, hepcidin, and ferritin subunits were assessed and classified according to ferritin levels and to siderosis identified by liver biopsy. RESULTS: A total of 67 patients with NAFLD were included in the study. MRI revealed mild iron overload in all patients (sensitivity, 73.5%; specificity, 70%). For mild (grade 1) siderosis, the transverse relaxation rate (R2*) threshold was 58.9 s-1 and the mean value was 72.5 s-1 (SD, 33.9), while for grades 2/3 it was 88.2 s-1 (SD, 31.9) (p < 0.001). The hepcidin threshold for siderosis was > 30.2 ng/mL (sensitivity, 87%; specificity, 82%). Ferritin H and ferritin L subunits were expressed similarly in patients with NAFLD, regardless of siderosis. There were no significant differences in laboratory test results between the groups, including glucose parameters and liver function tests. CONCLUSIONS: MRI relaxometry and serum hepcidin accurately assessed mild iron overload in patients with dysmetabolic iron overload syndrome.

Effects of clomiphene citrate on male obesity-associated hypogonadism: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Obesity causes secondary hypogonadism (HG) in men. Standard testosterone (T) replacement therapy improves metabolic parameters but leads to infertility. OBJECTIVE: To evaluate clomiphene citrate (CC) treatment of adult men with male obesity-associated secondary hypogonadism (MOSH). DESIGN: Single-center, randomized, double-blind, placebo-controlled trial. PARTICIPANTS: Seventy-eight men aged 36.5 ± 7.8 years with a body mass index (BMI) > 30 kg/m2, total testosterone (TT) ≤ 300 ng/dL, and symptoms in the ADAM questionnaire. INTERVENTION: Random allocation to receive 50 mg CC or placebo (PLB) for 12 weeks. OUTCOMES: (1) Clinical features: ADAM and sexual behavior questionnaires; (2) hormonal profile: serum TT, free T, estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG); (3) body composition: BMI, waist circumference, and bioelectric impedance analysis; (4) metabolic profile: blood pressure, fasting blood glucose, HbA1c, insulin, HOMA-IR, and lipid profile; (5) endothelial function: flow-mediated dilation of the brachial artery, quantitative assessment of endothelial progenitor cells and serum sICAM-1, sVCAM-1, and selectin-sE levels; (6) safety aspects: hematocrit, serum prostate-specific antigen, International Prostate Symptom Score, and self-reported adverse effects. RESULTS: There was an improvement in one sexual complaint (weaker erections; P < 0.001); increases (P < 0.001) in TT, free T, E2, LH, FSH, and SHBG; and improvements in lean mass (P < 0.001), fat-free mass (P = 0.004), and muscle mass (P < 0.001) in the CC group. CC reduced HDL (P < 0.001). No statistically significant differences were seen in endothelial function. CONCLUSIONS: CC appeared to effectively improve the hormonal profile and body composition. CC may be an alternative treatment for MOSH in adult men.

THE MASTICATORY SYSTEM OF THE OBESE: CLINICAL AND ELECTROMYOGRAPHIC EVALUATION.

UNLABELLED: Masticatory performance is determined not only through the speed of mastication, or by the quantity of food ingested; it also depends on the structures and functional integration of the stomatognathic system (SS). OBJECTIVES: This study investigated differences in the SS and orofacial motricity between obese and normal--weight women. METHOD: A total of 18 obese women, with an average age of 28 ± 7.3 years and an average body mass index (BMI) of 37.4 ± 5.1 Kg/m2, and 18 normal--weight women, with an average age of 26 ± 7.6 years and an average BMI of 20.7 ± 1.8 kg/m2, took part in the study. During the speech therapy evaluation, chewing, the number of chewing strokes, and swallowing were observed. The posture, mobility and tonus of lips and tongue, morphology, mobility and tonus of cheeks were designated as normal or altered. The electrical activity of the anterior temporalis, the masticatory muscle was evaluated for both groups using surface electromyography (EMG), which was expressed in microvolts (pV) and registered as Root Mean Squares. RESULTS: Significant differences were found between the two groups in clinical evaluation. In surface EMG, the obese group showed asymmetry of electrical activity of the anterior temporalis. CONCLUSION: This study suggests that speech therapist investigation of the SS should be combined with interdisciplinary obesity management.

The impact of obesity in hospitalized patients with COVID-19: a retrospective cohort study.

BACKGROUND: Obesity is believed to be a risk factor for COVID-19 and unfavorable outcomes, although data on this remains to be better elucidated. OBJECTIVE: To evaluate the impact of obesity on the endpoints of patients hospitalized due to SARS-CoV-2. METHODS: This retrospective cohort study evaluated patients hospitalized at a tertiary hospital (Hospital das Clínicas da Faculdade de Medicina da USP) from March to December 2020. Only patients positive for COVID-19 (real-time PCR or serology) were included. Data were collected from medical records and included clinical and demographic information, weight and height, SAPS-3 score, comorbidities, and patient-centered outcomes (mortality, and need for mechanical ventilation, renal replacement therapy, or vasoactive drugs). Patients were divided into categories according to their BMI (underweight, eutrophic, overweight and obesity) for comparison porpoise. RESULTS: A total of 2547 patients were included. The mean age was 60.3 years, 56.2% were men, 65.2% were white and the mean BMI was 28.1 kg/m2. SAPS-3 score was a risk factor for all patient-centered outcomes (HR 1.032 for mortality, OR 1.03 for dialysis, OR 1.07 for vasoactive drug use, and OR 1.08 for intubation, p < 0.05). Male sex increased the risk of death (HR 1.175, p = 0.027) and dialysis (OR 1.64, p < 0.001), and underweight was protective for vasoactive drug use (OR 0.45, p = 0.027) and intubation (OR 0.31, p < 0.003). CONCLUSION: Obesity itself was not an independent factor for worse patient-centered outcomes. Critical clinical state (indirectly evaluated by SAPS-3) appears to be the most important variable related to hard outcomes in patients infected with COVID-19.

The efficacy and safety of GLP-1 receptor agonists in youth with type 2 diabetes: a meta-analysis.

BACKGROUND: Glucagon-like peptide 1 receptor agonists have been proven to be effective in adults with diabetes and children with obesity. However, children with type 2 diabetes constitute an underrepresented subpopulation with limited treatment options. This meta-analysis aimed to determine more precise estimates of the efficacy and safety of glucagon-like peptide-1 agonists in pediatric type 2 diabetes mellitus. METHODS: Three databases were searched (PubMed, Embase, and Cochrane Central Register of Controlled Trials) for trials published until the end of March 2024. The search indexing terms included 3 categories: [1] type 2 diabetes mellitus [2], youth, and [3] glucagon-like peptide-1 receptor agonist (GLP-1 RA). Randomized controlled trials in youth with type 2 diabetes (age ≤ 18 years) that assessed anthropometric and metabolic parameters were included. A total of 1119 nonduplicate studies were retrieved, and 137 full-text articles were screened. The data were analyzed using mean differences (MDs) with 95% CIs and odds ratios (ORs) with 95% CIs. For outcomes with low heterogeneity, a fixed-effects model was used. Otherwise, we applied a random effects model. Our outcomes were Hb1Ac, fasting blood glucose (FBG), blood pressure, weight, and side effects. RESULTS: Five studies comprehending 415 children and adolescents were included. On average, GLP-1 RA reduced HbA1c levels (-1.01%; 95% CI, -1.26 to -0.76), fasting blood glucose levels (-1.88 mmol/L; 95% CI, -2.51 to -1.26), and body weight (-1.6 kg; 95% CI, -2.83 to -0.36). No significant reductions in systolic blood pressure (MD -0.19 mmHg; 95% CI, -3.9 to 3.52 mmHg) or diastolic blood pressure (MD 0.3 mmHg; 95% CI, -2.33 to 2.93 mmHg) were observed. Despite a higher incidence of side effects, withdrawal rates from the studies remained low. CONCLUSIONS: Within this specific population, GLP-1 RAs exhibit a notable association with substantial reductions in HbA1c, FBG, and body weight. The administration of these medications is concurrent with an elevated incidence of side effects, which are predominantly gastrointestinal and tolerable. TRIAL REGISTRATION: PROSPERO identifier: CRD42023393020.

Continuous Glucose Monitoring Captures Glycemic Variability After Roux-en-Y Gastric Bypass in Patients with and Without Type 2 Diabetes Mellitus: A Prospective Cohort Study.

PURPOSE: To evaluate glycemic variability (GV) using continuous glucose monitoring (CGM) in individuals with and without type 2 diabetes mellitus (T2DM) undergoing Roux-en-Y gastric bypass (RYGB). METHODS: This prospective cohort study compared the CGM data of fourteen patients with T2DM (n = 7) and without T2DM (n = 7) undergoing RYGB. After 6 months, these patients were compared to a non-operative control group (n = 7) matched by BMI, sex, and age to the T2DM group. RESULTS: Fourteen patients underwent RYGB, with a mean BMI of 46.9 ± 5.3 kg/m2 and an average age of 47.9 ± 8.9 years; 85% were female. After 6 months post-surgery, the total weight loss (TWL) was 27.1 ± 6.3%, with no significant differences between the groups. Patients without diabetes had lower mean interstitial glucose levels (81 vs. 94 and 98 mg/dl, p < 0.01) and lower glucose management indicator (GMI) (5.2 vs. 5.6 and 5.65%, p = 0.01) compared to the control and T2DM groups, respectively. The coefficient of variation (CV) significantly increased only in patients with diabetes (17% vs. 26.7%, p < 0.01). Both groups with (0% vs. 2%, p = 0.03) and without (3% vs. 22%, p = 0.03) T2DM experienced an increased time below range with low glucose (54-69 mg/dL). However, patients without T2DM had significantly less time in rage (70-180 mg/dL) (97% vs. 78%, p = 0.04). CONCLUSION: Significant differences in CGM metrics among RYGB patients suggest an increase in glycemic variability after surgery, with a longer duration of hypoglycemia, especially in patients without T2DM.

Consensus on pharmacological treatment of obesity in Latin America.

A panel of 10 experts in obesity from various Latin American countries held a Zoom meeting intending to reach a consensus on the use of anti-obesity medicines and make updated recommendations suitable for the Latin American population based on the available evidence. A questionnaire with 16 questions was developed using the Patient, Intervention, Comparison, Outcome (Result) methodology, which was iterated according to the modified Delphi methodology, and a consensus was reached with 80% or higher agreement. Failure to reach a consensus led to a second round of analysis with a rephrased question and the same rules for agreement. The recommendations were drafted based on the guidelines of the American College of Cardiology Foundation/American Heart Association Task Force on Practice. This panel of experts recommends drug therapy in patients with a body mass index of ≥30 or ≥27 kg/m2 plus at least one comorbidity, when lifestyle changes are not enough to achieve the weight loss objective; alternatively, lifestyle changes could be maintained while considering individual parameters. Algorithms for the use of long-term medications are suggested based on drugs that increase or decrease body weight, results, contraindications, and medications that are not recommended. The authors concluded that anti-obesity treatments should be individualized and multidisciplinary.

Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial.

In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. At 208 weeks, semaglutide was associated with mean reduction in weight (-10.2%), waist circumference (-7.7 cm) and waist-to-height ratio (-6.9%) versus placebo (-1.5%, -1.3 cm and -1.0%, respectively; P < 0.0001 for all comparisons versus placebo). Clinically meaningful weight loss occurred in both sexes and all races, body sizes and regions. Semaglutide was associated with fewer serious adverse events. For each BMI category (<30, 30 to <35, 35 to <40 and ≥40 kg m-2) there were lower rates (events per 100 years of observation) of serious adverse events with semaglutide (43.23, 43.54, 51.07 and 47.06 for semaglutide and 50.48, 49.66, 52.73 and 60.85 for placebo). Semaglutide was associated with increased rates of trial product discontinuation. Discontinuations increased as BMI class decreased. In SELECT, at 208 weeks, semaglutide produced clinically significant weight loss and improvements in anthropometric measurements versus placebo. Weight loss was sustained over 4 years. ClinicalTrials.gov identifier: NCT03574597 .

Down the rabbit hole: reviewing the evidence for primary prevention of cardiovascular disease in people with obesity.

Obesity is a prevalent chronic disorder and a well-known risk factor for cardiovascular disease. However, the evidence of treating obesity for primary prevention of major cardiovascular events is still scarce and controversial. In this review, we provided a comprehensive description of the current evidence in treating obesity regarding cardiovascular protection. Bariatric surgery appears to be the most robust method to reduce events in people without established cardiovascular disease. High compliance to lifestyle interventions can further reduce cardiovascular risk. Concerning pharmacological therapies, a post hoc analysis from SUSTAIN-6 and a meta-analysis from STEP trials suggest that semaglutide, a GLP-1 receptor agonist, could reduce cardiovascular events in people without established cardiovascular disease. The first study addressed specifically a high-risk population with diabetes and, the second, low- or intermediary-risk individuals without diabetes. Tirzepatide, a novel dual GIP/GLP-1 agonist, although not yet tested in specific cardiovascular outcomes trials, could be an alternative since it induces loss in weight similar to the achieved by bariatric surgery. Therefore, extrapolated data in distinct baseline cardiovascular risk populations suggest that these two drugs could be used in primary prevention with the aim of preventing cardiovascular events, but the grade of this evidence is still low. Specifically designed studies are needed to address this specific topic.

Plasma Concentration of Essential and Toxic Trace Elements After Brazil Nut Intake: Results from a Randomized Controlled Trial.

Brazil nut (BN) is a good source of essential nutrients, but little is known about the content of other components, such as toxic elements. Moreover, the high consumption of BN could probably contribute to increased levels of toxic and essential elements in the blood. Thus, this study aimed to evaluate the concentration of essential and toxic trace elements in BN and their concentration in plasma of obese women after regular intake of BN. A randomized controlled clinical trial was carried out with 55 subjects that were randomly assigned to either the Brazil nut group (BN) (n = 29) or the control group (CO) (n = 26) and followed up for 2 months. The BN group consumed one unit of Brazil nut per day, and the CO group did not receive any intervention. The concentration of essential elements (zinc, copper, manganese, and cobalt) and toxic (barium, lead, and cadmium) in BN samples and plasma of obese women (before and after the intervention) were determined by inductively coupled plasma mass spectrometry. Barium followed by copper, and manganese were the trace elements present in higher amounts in Brazil nuts. After the BN intervention period was observed an increase in plasma cadmium (p = 0.002) and a reduction of plasma manganese (p < 0.001) levels. In conclusion, our findings suggest that the regular consumption of BN from the Brazilian Amazon rainforest contributes to the intake of essential trace elements and can be considered safe regarding the content of heavy metals.

Treatment with Antiobesity Drugs in Weight Regain After Bariatric Surgery: a Retrospective Cohort Study.

BACKGROUND: Bariatric surgery is the most efficient treatment for obesity. However, in some cases, weight regain can occur. Currently, it is unknown the best antiobesity medication (AOM) for such clinical situation. This study aims to evaluate the effect of AOM in patients with weight regain after bariatric surgery. METHODS: A retrospective cohort study from December 2010 to July 2019 with patients submitted to bariatric surgery that had weight regain and received AOM for at least 2 years. RESULTS: Of 96 patients that had weight regain in the analyzed period and received AOM, 16 were excluded from the analysis due to non-compliance (n = 7), treatment failure (n = 5), intolerable side effects with all available AOM (n = 2), or interaction with other medications (n = 2). Eighty patients were included in the analysis. The mean age was 59.0 ± 10.1 years, 88.8% were female, 91.2% white, and most of them were submitted to gastric bypass (87.6%). The mean preoperative and nadir weight after surgery were 127.9 ± 25.5 kg and 84.7 ± 22.8 kg, respectively. At the initiation of AOM, the mean baseline weight was 99.4 ± 23.1 kg. After 2 years of follow-up, there was significant weight loss in the groups treated with topiramate-alone (- 3.2 kg), topiramate plus sibutramine (- 6.1kg), and orlistat-alone or in combination (- 3.9kg). No statistical difference was observed in the sibutramine-alone group. CONCLUSION: Topiramate (alone or associated with sibutramine) and orlistat (alone or in combination) promoted significant weight loss after 2 years of use in patients submitted to bariatric surgery with weight regain.

Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso).

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up,14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusion: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

Proposal of an obesity classification based on weight history: an official document by the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO).

Obesity is a chronic disease associated with impaired physical and mental health. A widespread view in the treatment of obesity is that the goal is to normalize the individual's body mass index (BMI). However, a modest weight loss (usually above 5%) is already associated with clinical improvement, while weight losses of 10%-15% bring even further benefits, independent from the final BMI. The percentage of weight reduction is accepted as a treatment goal since a greater decrease in weight is frequently difficult to achieve due to metabolic adaptation along with environmental and lifestyle factors. In this document, the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO) propose a new obesity classification based on the maximum weight attained in life (MWAL). In this classification, individuals losing a specific proportion of weight are classified as having "reduced" or "controlled" obesity. This simple classification - which is not intended to replace others but to serve as an adjuvant tool - could help disseminate the concept of clinical benefits derived from modest weight loss, allowing individuals with obesity and their health care professionals to focus on strategies for weight maintenance instead of further weight reduction. In future studies, this proposed classification can also be an important tool to evaluate possible differences in therapeutic outcomes between individuals with similar BMIs but different weight trajectories.

Pharmacokinetics of oral levonorgestrel and ethinylestradiol in women after Roux-en-Y gastric bypass surgery.

BACKGROUND: Most patients undergoing Roux-en-Y gastric bypass (RYGB) are women in reproductive age. It is not known if bariatric surgery affects the pharmacokinetics of oral contraceptives. OBJECTIVES: The primary objective was to evaluate ethinylestradiol (EE) and levonorgestrel (LNG) absorption in women undergoing RYGB, compared with nonoperated controls matched by age and body mass index (BMI). A secondary objective was to assess whether the time since surgery and BMI in the postoperative period influenced the absorption parameters. SETTING: University hospital, Brazil. METHODS: This study was designed to compare the maximum plasma concentration (Cmax), the time to the peak plasma level (Tmax), the area under the curve (AUC0-8 and AUC0-∞) after a single dose of a combined oral contraceptive with 0.03 mg EE and 0.15 mg LNG among 20 women after RYGB and 20 controls. Blood samples were obtained for 8 hours. RESULTS: The mean LNG AUC0-8 and LNG AUC0-∞ were higher in RYGB group (P = .048 and P = .004, respectively). We found a positive correlation for LNG AUC0-8 (P = .045) and AUC0-∞ (P = .004) and the time since surgery, and we found a negative correlation for LNG Cmax (P = .018), AUC0-8 (P = .003), and AUC0-∞ (P = .001) and BMI. CONCLUSION: No significant differences were found in oral EE pharmacokinetics. The operated group showed higher mean LNG AUC0-8 and AUC0-∞ but it was not considered clinically significant. The present study suggests that RYGB may not affect EE and LNG absorption.

Cardiovascular safety of naltrexone and bupropion therapy: Systematic review and meta-analyses.

Despite being approved for clinical use, evidence of cardiovascular safety (CV) is lacking for treatment with bupropion, naltrexone, or their combination (B-N). The purpose of the study is to determine the relationship between these treatments and the risk of major cardiovascular adverse events (MACE). Phase 3 randomized clinical trials (RCT) evaluating bupropion, naltrexone, or B-N versus control with reported incidence of MACE. The meta-analysis included 12 RCTs, 69% for weight loss and 29% for smoking cessation, with 19,176 patients and 7354 patient-years who were randomized to an active treatment (bupropion [n = 2965] or B-N [n = 6980] or naltrexone [n = 249]) versus control (placebo [n = 6968] or nicotine patch [n = 2014]). The mean age was 54 ± 8 years (55% female), and the baseline BMI was 32 ± 5 kg/m2 . The additive network meta-analysis model for random effects showed no association between bupropion, B-N, or naltrexone and MACE (odds ratio [OR] = 0.90 [95%CI 0.65-1.25], p = 0.52; OR = 0.97 [95%CI 0.75-1.24], p = 0.79; OR = 1.08 [95%CI 0.71-1.63], p = 0.73, respectively; I2 = 0%, p = 0.86). Meta-regression analyses showed no significant association between MACE and potential confounders from RCT demographic disparities (p = 0.58). The statistical power (post hoc two-tailed) for non-inferiority was 91%, giving a strong probability of validity. Naltrexone, bupropion, or B-N is not associated with the incidence of MACE as compared with placebo.

Efficacy and safety of evogliptin in the treatment of type 2 diabetes mellitus in a Brazilian population: a randomized bridging study.

BACKGROUND: Evogliptin (EVO) is a potent and selective dipeptidyl peptidase-4 inhibitor (DPP4i) developed for the treatment of type 2 diabetes mellitus (T2DM). DPP4is are known to exhibit a better glucose-lowering effect in Asians compared to other ethnic groups. Once EVO's clinical development program was conducted in Asian patients, this bridging study was designed to validate for the Brazilian population the efficacy and safety of the approved dose regimen (once-daily 5.0 mg). METHODS: In this randomized, double-blind, double-dummy, parallel trial, 146 patients with T2DM with inadequate glycemic control on diet and exercise (7.5% ≤ HbA1c ≤ 10.5%) were randomly assigned to a 12-week once-daily treatment with EVO 2.5 mg (N = 35), EVO 5 mg (N = 36), EVO 10 mg (N = 36), or sitagliptin (SITA) 100 mg (N = 39). Absolute changes (Week 12-baseline) in HbA1c, fasting plasma glucose (FPG) and body weight (BW) were obtained. One-sided one sample t test was used to determine if mean HbA1c reduction in each group was < - 0.5% (beneficial metabolic response). An analysis of covariance estimated the change in HbA1c and FPG adjusted by baseline HbA1c, FPG, body mass index (BMI) and study site. Response rates to treatment were also established. No between-group statistical comparisons were planned. RESULTS: HbA1c mean reductions were - 1.26% (90% CI - 1.7%, - 0.8%), - 1.12% (90% CI - 1.4%, - 0.8%), - 1.29% (90% CI - 1.6%, - 1.0%), and - 1.15% (90% CI - 1.5%, - 0.8%) in groups EVO 2.5 mg, EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. FPG levels showed a mean increase of 10.89 mg/dL in group EVO 2.5 mg, with significant mean reductions of - 18.94 mg/dL, - 21.17 mg/dL, and - 39.90 mg/dL in those treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. BW showed significant reductions of approximately 1 kg in patients treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg. Mean adjusted reductions of HbA1c and FPG levels confirmed the significant clinical benefit of all study treatments. The clinical benefit of EVO's "target" dose (5 mg) was confirmed. No safety concerns were identified. CONCLUSIONS: These results validate for the Brazilian population the approved dose regimen of EVO (once-daily 5 mg).Trial registration ClinicalTrials.gov Identifier: NCT02689362 (first posted on 02/23/2016).