Greater Reduction In Body Weight Research Articles

An addiction-based mobile health weight loss intervention: protocol of a randomized controlled trial

BackgroundThe notion of obesity as an addictive process is controversial. However, studies show that between 5.9 and 30.7% of adolescents with obesity report food or eating addiction. Few weight management interventions have tested techniques based on addiction medicine principles. MethodsThis multi-center randomized control trial (RCT) is designed to test the effectiveness of a mobile health (mHealth) weight-loss intervention based on addiction principles, such as withdrawal and tolerance, in a sample of 180 adolescents (ages 14–18) recruited from four pediatric weight management clinics in Southern California. Akin to a Multiphase Optimization Strategy (MOST) design evaluating multicomponent behavioral interventions, we will compare the combination of an app + phone coaching (App+Coach) to app alone (App) and in-clinic multi-disciplinary (Clinic) intervention arms.The primary outcome is mean change in zBMI and %BMIp95 over 18 months. We hypothesize that youth who receive App+Coach will have a greater reduction in body weight over the 18-month study period at a lower cost than standard of care models. Secondary outcomes include adherence to treatment regimen, intervention satisfaction, effect of the intervention on metabolic factors and activity level. We will also explore potential moderators of intervention effectiveness such as addictive eating habits, self-regulation and executive functioning. ConclusionsNew and creative approaches are needed to address pediatric obesity. If successful, this RCT may provide an innovative and cost-effective mHealth approach, based on addiction methods, for weight loss among adolescents with overweight and obesity.

Randomized controlled trial assessing two commercial weight loss programs in adults with overweight or obesity.

SummaryObjectiveLifestyle interventions remain the cornerstone for obesity treatment. Commercial programs offer one weight loss approach, yet the efficacy of few such programs have been rigorously investigated. The purpose of this study was to evaluate the efficacy of two commercial weight‐loss programs, both utilizing pre‐portioned meal replacements (MRs) and different levels of behavioural support, compared to a self‐directed control diet in adults with overweight and obesity.MethodsIn this 16‐week study, participants were randomized to the low‐calorie OPTAVIA® 5&1 Plan® with telephone coaching (OPT), the reduced‐calorie Medifast® 4&2&1 self‐guided plan (MED), or a self‐directed, reduced‐calorie control diet. Differences in weight, body composition (DXA) and body circumferences, all measured monthly, were assessed by analysis of covariance with sex and baseline measures as covariates.ResultsOf 198 participants randomized (80.8% female, BMI 34.2 kg/m2, 45.7 years), 92.3% completed the study. The OPT and MED groups had significantly greater reductions in body weight (−5.7% and − 5.0%, respectively, p < 0.0001), fat and abdominal fat mass (p < 0.0001) and waist and hip circumferences (p ≤ 0.003) than control at 16 weeks. Weight change was correlated with MR usage and completion of coaching support calls.ConclusionsBoth structured commercial programs were more efficacious than a self‐directed, reduced‐calorie diet for weight loss and other anthropometric measures. Evidence‐based commercial programs can be an important tool to help adults with overweight and obesity lose clinically relevant amounts of weight.

Efficacy and tolerability of exenatide once weekly over 7 years in patients with type 2 diabetes: An open-label extension of the DURATION-1 study

AimsTo investigate the glycemic efficacy, effects on cardiovascular risk factors, and safety of exenatide once weekly (QW) in patients with type 2 diabetes over 7 years in the DURATION-1 study. MethodsPatients were initially randomized to exenatide QW 2 mg or exenatide twice daily for 30 weeks, after which they received open-label, open-ended treatment with exenatide QW 2 mg for up to 7 years. Efficacy analyses included changes from baseline in glycated hemoglobin (HbA1C) and cardiovascular risk factors. ResultsOf 295 patients in the intention-to-treat population, 122 (41%) completed 7 years of treatment. Patients in the 7-year completer population showed sustained glycemic improvements from baseline (7-year least-squares mean [LSM] change in HbA1C, −1.53%) and significant improvements in several cardiovascular risk factors, including body weight, diastolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Seven-year completers who received no additional glucose-lowering therapies (n = 65 [53%]) had similar improvements in HbA1C, and numerically greater reductions in body weight (7-year LSM change, −6.46 kg vs −3.87 kg), compared with the overall cohort. There were no unexpected safety findings. ConclusionsTreatment with exenatide QW for 7 years was associated with sustained improvements in glycemic control and several cardiovascular risk factors.

Comparison of the Effectiveness of Online and Face-to-Face Weight-loss Interventations in the Workplace: Evidence from Malaysia

A structured weight management programme at a workplace may help in reducing the prevalence of overweight and obesity. Therefore, this intervention study was to determine the effectiveness of weight loss programmes including face-to-face, online and control group at workplace among employees who are overweight and obese. A total of 108 overweight and obese adults were recruited and randomly divided into three groups (face-to-face group (FT), n=38; online group (OG), n=31; control group (CG), n=39). In the FT group, the participants took part in health talks, interactive activities and counselling; the OG group was given access to an online weight management program and the CG group was provided with educational booklets on weight loss. All information given was related to nutrition, physical activity and motivation to reduce weight. Body weight, body mass index (BMI), waist circumference (WC), body fat percentage, dietary intake, fasting lipid profile and glucose levels were assessed at baseline and 4 months. The FT group showed greater reduction in body weight (-5.80 kg) compared to OG (-1.12 kg) and CG (-1.82 kg). Significant interaction effects were found for BMI, WC, fasting serum triglycerides, HDL-cholesterol and total cholesterol/HDL-cholesterol ratio (all p<0.05), with the FT group showing the biggest improvements, compared to the other groups. The face-to-face weight management program offered in the workplace showed to be the most effective at improving anthropometric profile, fasting serum triglycerides, HDL-C, total cholesterol/HDL-C ratio, and dietary intake among overweight and obese employees.

SGLT-2 Inhibitors and DPP-4 Inhibitors as Second-Line Drugs in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Clinical Trials.

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors are both novel and second-line therapies in type 2 diabetes mellitus, yet no well-rounded comparison of these two drugs has been published. Upon searching randomized controlled trials in databases from inception to July 2018, we collected studies on the efficacy or safety of SGLT-2 inhibitors compared with those of DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. A total of 12 randomized controlled studies including 4342 patients were included in this meta-analysis. Compared with DPP-4 inhibitors, SGLT-2 inhibitors achieved greater reductions in HbA1c (SMD -0.22; 95% CI: -0.30, -0.14; p=0.000) and fasting plasma glucose (SMD -0.48; 95% CI: -0.56, -0.41; p=0.000). In addition, these reductions increased with a prolonged treatment duration from 12 to 78 weeks. Geographically, significant reductions of SGLT-2 inhibitors in HbA1c and FPG were found in North America and Europe, but not in Asia. Furthermore, SGLT-2 inhibitors showed greater reductions in body weight (SMD -0.72; 95% CI: -0.81, -0.63; p=0.000) from baseline, with an increased incidence of genital infections (OR 4.49; 95% CI: 2.96, 6.83; p=0.000) and pollakiuria (OR 2.24; 95% CI: 1.05, 4.79; p=0.037) and a decreased incidence of hypertension and hyperglycemia. Overall, the current meta-analysis demonstrated that compared to DPP-4 inhibitors, SGLT-2 inhibitors have beneficial effects on HbA1c, FPG, body weight, SBP, DBP, and HDL-cholesterol in patients with type 2 diabetes. However, SGLT-2 inhibitors are associated with increased total cholesterol and LDL-cholesterol and a higher incidence of genital infections and pollakiuria.

A proof-of-concept study to evaluate the efficacy and safety of BTI320 on post-prandial hyperglycaemia in Chinese subjects with pre-diabetes

BackgroundGalactomannan(s) are plant-derived fiber shown to reduce post-prandial blood glucose by delaying intestinal absorption of carbohydrates and slowing down gastric emptying. We examined glucose-lowering effects of BTI320, a propriety fractionated mannan(s) administered as a chewable tablet before meal in a proof-of-concept study in Chinese subjects with prediabetes.MethodsSixty Chinese adults aged 18–70 years with either impaired fasting glucose, impaired glucose tolerance, or glycated haemoglobin 5.7–6.4% (39-46 mmol/mol), were randomly assigned in 2:2:1 ratio to either BTI320 8 g (high dose), BTI320 4 g (low dose) or matching-placebo three times daily before meal for 16 weeks. The primary endpoint was change in fructosamine in subjects treated with BTI320 compared with placebo from baseline to week 4. Indices of glycaemic variability based on continuous glucose monitoring (CGM) and standard meal tolerance test were explored in secondary analyses.ResultsOf 60 subjects randomized, 3 subjects discontinued study treatment prematurely. In intention-to-treat analysis, no significant differences in change in serum fructosamine between low or high dose BTI320 and placebo were observed. Using random effect models, adjusted for variability by meals, treatment with low dose BTI320 was associated with reduction in 1-h (p < 0.01), 2-h (p = 0.01) and 3-h (p = 0.02) post-prandial incremental glucose area-under-curve and post-meal maximum glucose (p = 0.03) compared with placebo. Subjects receiving low dose BTI320 had greater body weight reduction than placebo group.ConclusionsBTI320 did not change fructosamine levels compared with placebo. BTI320 reduced glycaemic variability based on CGM indices.Trial registrationThe study was registered at www.clinicaltrials.gov, reference number NCT02358668 (9 February 2015).

Continuous versus intermittent administration of furosemide in acute decompensated heart failure: a systematic review and meta-analysis.

Diuretic therapy is important in critically ill patients because fluid overload impairs organ function and increases mortality. Compared to intermittent administration, continuous infusion of loop diuretics is theoretically superior in terms of diuresis and electrolyte balance. However, the available evidence is susceptible to carryover diuretic effects and resistance in earlier crossover trials. Consequently, we conducted a systematic review and meta-analysis of parallel-group randomized controlled trials to compare these two strategies in adults with acute decompensated heart failure. We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from their inceptions to May 26, 2018. We pooled the data using a random effects model. Our primary outcomes were all-cause mortality, length of hospital stay, and body weight reduction. We analyzed 12 parallel-group randomized controlled trials involving 923 patients. Compared with intermittent administration, continuous infusion of furosemide was not associated with an improvement in all-cause mortality (risk ratio 1.19; 95% confidence interval [CI], 0.65 to 2.16), length of hospital stay (weighted mean difference [WMD] - 0.88days; 95% CI, - 2.76 to 1.01), or 24-h urine output (WMD 489.17mL; 95% CI, - 183.18 to 1161.51), but was significantly associated with a greater body weight reduction (WMD 0.63kg; 95% CI, 0.23 to 1.02). No differences in hypokalemia, hyponatremia, increased serum creatinine level, and hypotension were noted. Continuous infusion of furosemide, compared to intermittent administration, is associated with a greater body weight reduction and potential increase in 24-h urine output. The limited available evidence suggests no difference in adverse events between both strategies. Trial registration: PROSPERO (CRD42017083878).

Abstract 4919: Preclinical activity of SDX-7320 in mouse models of obesity and obesity-driven cancer

Abstract Cancer patients who are obese face a greater risk of dying from cancer compared to nonobese patients (Calle, 2003). Obesity is believed to contribute to metastasis and progression of cancer via multiple mechanisms: increased secretion of the adipose tissue hormone leptin, decreased secretion of adiponectin, increased production of estrogen in adipose tissue, and elevated insulin (secondary to peripheral insulin resistance) as well as the local effects of inflammatory cytokines (Gucalp, 2016). Small-molecule inhibitors of methionine aminopeptidase type 2 (MetAP2) have previously demonstrated clinical activity in oncology (Kudelka, 1998) as well as obesity/type 2 diabetes (Hughes, 2013; Kim, 2015). However, development of some small-molecule MetAP2 inhibitors has been hampered by CNS side effects (Bhargava, 1999). SDX-7320 is a copolymer-drug conjugate of a novel fumagillin-derived MetAP2 inhibitor (SDX-7539) attached via a cleavable linker to a hydroxypropylmethacrylamide (HPMA) backbone, intended to limit CNS penetration and therefore reduce CNS toxicity. In vitro MetAP2 binding assays showed that SDX-7320 was unable to bind to MetAP2 while SDX-7539 was a potent binder (apparent IC50 = 0.13 nM), indicating that cleavage of SDX-7320 is required for biologic activity. SDX-7539 inhibited proliferation of human umbilical vein endothelial cells (HUVECs) with an apparent IC50 = 0.2 nM. The preclinical efficacy of SDX-7320 was evaluated in mouse models of obesity/insulin resistance and also in syngeneic tumor models coupled with high fat diet-induced obesity (DIO)/metabolic dysfunction. Obesity and insulin resistance were induced in C57Bl/6 mice by feeding them a high-fat diet (HFD) for at least 12 weeks. SDX-7320 was dosed subcutaneously every 4 days (for 28 days) into DIO mice or control mice fed a low-fat diet. SDX-7320 caused significant reduction in body weight and fat mass in obese mice while also reversing insulin resistance relative to controls. In addition, SDX-7320 caused greater reduction in body weight in obese mice relative to lean mice. Circulating levels of leptin and insulin were reduced while levels of adiponectin were increased in response to SDX-7320. In mouse models of obesity-accelerated tumor growth, SDX-7320 was more efficacious in obese relative to lean mice harboring subcutaneous B16F10 melanoma or EO771 mammary gland tumors. These effects occurred without any signs of neurotoxicity. SDX-7320, currently in phase I (solid tumors; all-comers; NCT02743637), is being developed for the treatment of cancers whose progression is accelerated in the setting of obesity and host metabolic dysfunction, termed “metabo-oncology.” Citation Format: Peter Cornelius, John S. Petersen, Benjamin Mayes, David Turnquist, Kimberly Sullivan, Alfred Anderson-Villaluz, Robert Lutz, Sara Little, Andrew Slee, Bradley J. Carver, James Shanahan. Preclinical activity of SDX-7320 in mouse models of obesity and obesity-driven cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4919.

Comparing the efficacy of therapeutic packages in Persian Medicine with Classical Medicine in overweight patients: a randomized clinical trial.

BackgroundObesity is a major risk factor for many diseases. In Persian Medicine, much emphasis has been put on the balanced weight that maintains health. Therefore, the treatment of obesity is a top priority for health care in Persian and Classical Medicine.ObjectiveTo compare the efficacy of therapeutic packages in Persian Medicine with Classical Medicine in overweight treatment.MethodsThis randomized clinical trial was conducted at Ghaem Hospital in Mashhad, Iran, from August 22, 2016 to December 20, 2016. Sixty-nine overweight women with body mass index (BMI) of 27–29.9 and waist circumference more than 88 cm based on inclusion and exclusion criteria, were included in the study. To control bias in sampling, with considering that the age variable is an interventional factor in the process of effective treatment, in addition to using the random allocation method, the population were studied in three groups of 18–30 years old, 31–50 years old and >50 years old, who were classified by blocking method, and three types of treatment interventions were performed in each age group: Group A (Classical diet and orlistat), Group B (Persian diet and MDB) and Group C (classical diet and MDB). Calorie consumption was equivalent in the three groups. Blinding was done only for patients. The treatment period was three months in all three groups. Subsequently, we analyzed the effectiveness of the therapeutic packages on anthropometric index, body composition and laboratory parameters in the three groups. The data were analyzed using SPSS version 16. We used descriptive statistics, Kolmogorov–Smirnov, ANOVA, paired-samples t-test, non-parametric Wilcoxon test and regression methods for the analyses of primary and secondary outcomes.ResultsAlthough anthropometric index and fat mass decreased highly significantly in all three intervention groups (p<0.001), the B group led to a further decrease in BMI (Mean ± SD: 1.61±1.03), weight (Mean ± SD: 4.79±2.26), waist circumference (Mean ± SD: 4.25±0.59) and Fat mass (Mean ± SD: 3.24±2.70), compared with the other two groups. Lipid profile and FBS in groups B and C had significant decrease before and after the intervention, but Group A had no significant effect before or after the intervention. Other laboratory parameters did not change significantly before or after the treatment in the three groups.ConclusionIn this study, Classical Medicine and Persian Medicine had the same levels of effectiveness but Persian Medicine brought a greater reduction in body weight, fat mass%, lipid profile and fasting blood glucose than Classical Medicine during the study period. So Persian Medicine can be effective in weight loss as an alternative therapy, but more studies are needed.Trial registrationThe trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: (IRCT 2016041927477N1).FundingThis paper is supported by a grant from the Research Council, Mashhad University of Medical Sciences, Mashhad, Iran.

Improved Cardiovascular and Renal Outcomes in the CANagliflozin CardioVascular Assessment Study (CANVAS) Program Irrespective of Baseline (BL) Body Mass Index (BMI)

Overweight and obesity increases the risk of heart and kidney disease. The effects of canagliflozin (CANA) in patients with BL BMI &amp;lt;30 or ≥30 kg/m2 was a prespecified analysis in the CANVAS Program. CANA reduced CV and renal outcomes in patients with T2D and high CV risk (N = 10,142). At BL compared to patients with BMI &amp;lt;30 kg/m2, more patients with BMI ≥30 kg/m2 had SBP ≥140 or DBP ≥90 mmHg (47.9% vs. 40.3%) and were taking RAAS inhibitors (83.8% vs. 74.6%). Effects of CANA on the primary outcome (CV death, nonfatal myocardial infarction, or nonfatal stroke) and other CV outcomes were consistent between BMI subgroups (Fig). CANA decreased progression of albuminuria in both BMI subgroups with the effect appearing greater in patients with BMI ≥30 kg/m2. Further statistical testing did not show a qualitative interaction (Gail-Simons P = 0.875). The comparative benefits of CANA on albuminuria in patients with higher BMI may be due to greater reductions in body weight (placebo-subtracted difference at 1 y: -2.1 and -2.8 kg for BMI &amp;lt;30 and ≥30 kg/m2) and BP (SBP: -4.2 and -4.6 mmHg; DBP: -1.0 and -1.7 mmHg for BMI &amp;lt;30 and ≥30 kg/m2); HbA1c reductions were similar with BMI &amp;lt;30 and ≥30 kg/m2 (-0.60% and -0.63%). While small statistical heterogeneity may exist, BMI &amp;lt;30 vs. ≥30 kg/m2 does not appear to be a major determinant of the observed improvements in CV outcomes with CANA. Disclosure H. Bays: Research Support; Self; Amgen Inc. L. Van Gaal: Advisory Panel; Self; Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen J &amp; J, Merck MSD, Novo Nordisk, Sanofi and Servier/Intarcia. Speaker's Bureau; Self; Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen J &amp; J, Merck MSD, Novo Nordisk, Sanofi and Servier/Intarcia. Research Support; Self; EU (Hepadip &amp; Resolve consortium) and National Research Funds. S. Aravind: None. N. Aggarwal: None. R. Violante: Advisory Panel; Self; Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, AstraZeneca, Sanofi-Aventis. Research Support; Self; Novo Nordisk Inc., Merck Sharp &amp; Dohme Corp., Eli Lilly and Company, Janssen Pharmaceuticals, Inc. A. Slee: Other Relationship; Self; Janssen Scientific Affairs, LLC. W. Shaw: Employee; Self; Janssen Research &amp; Development. K.W. Mahaffey: Research Support; Self; Afferent, Amgen, AstraZeneca, Daiichi, Ferring, Google (Verily), Janssen, Medtronic, Merck, Novartis, Sanofi, and St. Jude. Consultant; Self; Ablynx, AstraZeneca, BAROnova, Bio2 Medical, Boehringer Ingelheim, Bristol-Myers Squibb, Cardiometabolic Health Congress, Cubist, Eli Lilly, Elsevier, Epson, GlaxoSmithKline, Janssen, Merck, Mt. Sinai, Radiometer, Springer Publishing, The Medicines Company, Theravance, Vindico, and WebMD. Stock/Shareholder; Self; BioPrint Fitness. D. de Zeeuw: Other Relationship; Self; AbbVie Inc., Astellas Pharma US, Inc., Eli Lilly and Company, Fresenius SE &amp; Co. KGaA, Janssen Scientific Affairs, LLC., Boehringer Ingelheim GmbH, Bayer AG, Mitsubishi Tanabe Pharma Corporation. D.R. Matthews: Other Relationship; Self; Janssen Scientific Affairs, LLC., Novo Nordisk Inc., GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Eli Lilly and Company, Sanofi-Aventis, Servier, Aché Laboratories.

Initial Beta-Hydroxybutyrate Elevation in Relation to Subsequent Weight Loss in Type 2 Diabetes via the SGLT2 Inhibitor Tofogliflozin

The elevation of ketones is clinically concerned in the use of SGLT2 inhibitor (SGLT2i), however little is known about the association between that elevation and subsequent clinical process. We aimed to clarify the association of the initial beta-hydroxybutyrate (BHB) elevation via the SGLT2i, tofogliflozin with subsequent weight loss in type 2 diabetes participants. Analyzed were 774 type 2 diabetes participants who received tofogliflozin in two phase 3 studies. The participants were divided into four groups according to the quartiles for their change in BHB after 4 weeks of tofogliflozin therapy. The adjusted assessments of variables were analyzed using an analysis of covariance model with the quartiles, their baseline values, age, sex, and eGFR as covariates. BHB levels significantly increased (mean: +107.1 µmol/L) from baseline to week 4. Those changes in the first (Q1), second (Q2), third (Q3), and fourth (Q4) quartiles, respectively, were -33.7, +31.4, +98.0, and +331.1 µmol/L. Glycemic control at baseline was poorer, while CPI was lower within the higher quartiles. The difference of BHB changes among the quartiles was maintained during tofogliflozin therapy. At week 52, the increase of BHB levels from baseline was significant (+142.7 µmol/L) in Q4, but not changed in Q1. The weight loss at week 52 in Q4 (least square mean: -3.6 kg) was greater than in Q1 (-2.4 kg) although the improvement of hyperglycemia was identical. Furthermore, the reduction in waist circumference and increase in adiponectin were greater in Q4. And the increase in fasting free fatty acid was also greater in Q4, but not changed in Q1. The distinct response of BHB elevation was observed early after the SGLT2i, tofogliflozin therapy. The higher initial BHB elevation resulted in the greater reduction in body weight, especially fat mass via lipolysis. The progressive weight loss might be clinically associated with one of the signs of the higher ketone elevation. Disclosure Y. Sato: None. K. Nunoi: None. K. Kaku: Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Mitsubishi Tanabe Pharma Corporation, MSD K.K.. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Ono Pharmaceutical Co., Ltd.. Advisory Panel; Self; Sanwa Kagaku Kenkyusho Co., Ltd.. Speaker's Bureau; Self; Taisho Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceuticals, Japan Inc., Kowa Pharmaceuticals, Japan Inc.. Advisory Panel; Self; Astellas, Japan Inc. A. Yoshida: Employee; Self; Kowa Pharmaceutical Co. Ltd. H. Suganami: Employee; Self; Kowa Company, Ltd..

Effect of weight loss on circulating fatty acid profiles in overweight subjects with high visceral fat area: a 12-week randomized controlled trial

BackgroundSignificant associations between visceral fat and alterations in plasma fatty acids have been identified in overweight individuals. However, there are scant data regarding the relationships of the visceral fat area (VFA) with the plasma fatty acid profiles and desaturase activities following weight loss. We investigated the effect of weight loss with mild calorie restriction on the circulating fatty acid profiles and desaturase activities in nondiabetic overweight subjects with high VFA.MethodsEighty overweight subjects with high VFA (L4 VFA ≥100 cm2) were randomized into the 12-week mild-calorie-restriction (300 kcal/day) or control groups.ResultsComparison of the percent of body weight changes between groups revealed that the weight-loss group had greater reductions in body weight. The VFA decreased by 17.7 cm2 from baseline in the weight-loss group (P < 0.001). At follow-up, the weight-loss group showed greater reductions in serum triglycerides, insulin, and HOMA-IR than the control group. Significantly greater reductions in total saturated fatty acids, palmitic acid, stearic acid, total monounsaturated fatty acids, palmitoleic acid, oleic acid, eicosadienoic acid, and dihomo-γ-linolenic acid levels were detected in the weight-loss group compared with the control group after adjusting for baseline values. Following weight loss, C16 Δ9-desaturase activity was significantly decreased and Δ5-desaturase activity was significantly increased, and the changes were greater in the weight-loss group than in the control group.ConclusionsThe results suggest that mild weight loss improves abdominal obesity, overall fatty acid profiles, and desaturase activities; therefore, mild calorie restriction has potential health benefits related to obesity-related diseases in overweight subjects with high VFA.Trial registrationNCT02992639. Retrospectively registered 11 December 2016.

An indirect treatment comparison of the efficacy of insulin degludec/liraglutide (IDegLira) and insulin glargine/lixisenatide (iGlarLixi) in patients with type 2 diabetes uncontrolled on basal insulin

Aims: To obtain estimates of the relative treatment effects between insulin degludec/liraglutide (IDegLira) and insulin glargine U100/lixisenatide (iGlarLixi) in patients with type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin therapy.Materials and methods: Data from phase 3 trials providing evidence for estimating the relative efficacy and safety of IDegLira vs iGlarLixi in patients uncontrolled on basal insulin-only regimens were used in this analysis. Outcomes of interest were changes in HbA1c, body weight and insulin dose, and rate ratio of hypoglycemia. The indirect comparison of the reported trial findings followed the principles of Bucher et al.Results: IDegLira was estimated to provide a 0.44 [95% CI = 0.17–0.71] %-point reduction in HbA1c compared with iGlarLixi. Body weight was reduced by 1.42 [95% CI = 0.35–2.50] kg with IDegLira compared with iGlarLixi. Insulin dose was comparable between the two interventions. The rate of severe or blood glucose-confirmed (self-measured plasma glucose [SMPG] ≤ 3.1 mmol/L) hypoglycemia with IDegLira was approximately half that of iGlarLixi (rate ratio = 0.51 [95% CI = 0.29–0.90]). However, using the American Diabetes Association definition of documented symptomatic hypoglycemia (SMPG ≤3.9 mmol/L) the rate was comparable between the two treatments (rate ratio = 1.07 [95% CI = 0.90–1.28]).Limitations: The assumptions made in the indirect comparison and differences between the included trials in baseline HbA1c levels, previous use of sulfonylureas, definitions of hypoglycemia, presence or absence of run-in period, the different duration of the trials, and the cross-over design of one of the trials.Conclusions: The results of this indirect treatment comparison demonstrate that, among patients with T2DM uncontrolled on basal insulin, treatment with IDegLira results in a greater reduction of HbA1c and a greater reduction in body weight compared with iGlarLixi at similar insulin doses.

Effects of 12-week supplementation of Citrus bergamia extracts-based formulation CitriCholess on cholesterol and body weight in older adults with dyslipidemia: a randomized, double-blind, placebo-controlled trial

BackgroundsRecent experiments suggest that Citrus bergamia extracts could benefit people with dyslipidemia and obesity but this needs to be further validated.MethodsA total of 98 people age-matched older adults (65 years) with elevated blood lipids were enrolled to receive 12-week supplementation of a Citrus bergamia extracts-based formulation (CitriCholess)(n = 48) and placebo (n = 50).ResultsNo group differences were found in baseline bodyweight, body mass index (BMI), blood cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and glucose levels. CitriCholess supplementation resulted in lower levels than placebo in TG (1.83 ± 0.92 vs. 1.95 ± 1.34 mmol/L, P = 0.612), TC (5.14 ± 0.98 vs. 5.44 ± 0.77 mmol/L, P = 0.097), and LDL-C (3.13 ± 0.74 vs. 3.43 ± 0.62 mmol/L, P = 0.032). Compared to placebo, CitriCholess also resulted in greater reductions in body weight (−0.604 ± 0.939 vs. 0.06 ± 0.74 kg, P < 0.01), waist circumferences (−0.60 ± 1.349 cm vs. -0.16 ± 1.503 cm, P < 0.01) and BMI (−0.207 ± 0.357 vs. 0.025 ± 0.274, P < 0.01). Additionally, females had a significantly higher level of HDL-C than males. TC was significantly correlated with LDL-C, and to a less degree, with TG. TG was inversely correlated with HDL-C. Body weight and waist circumference were negatively correlated with HDL-C and positively correlated with glucose.Conclusion12-week supplementation of CitriCholess could benefit lipid metabolism and weight management in old adults with dyslipidemia.

Semaglutide Reduces Body Weight Across Baseline BMI Subgroups Across SUSTAIN 1–5

Semaglutide, a GLP-1 analog in development for once-weekly subcutaneous treatment of T2D, demonstrated superior reductions in HBA1c levels and body weight (BW) across SUSTAIN 1–5 clinical trials. A post-hoc analysis of SUSTAIN 1–5 data was conducted to assess semaglutide efficacy (0.5 mg; 1.0 mg) vs comparators (placebo, sitagliptin, exenatide ER, insulin glargine) by baseline BMI (kg/m2) subgroups (<25, 25-<30, 30-<35, ≥35). The role of baseline BMI in semaglutide-induced BW loss was investigated. Across the SUSTAIN trials, semaglutide reduced mean BW from baseline in all BMI subgroups vs comparators, ranging between decreases of 2.5–5.7 kg with semaglutide 0.5 mg and 2.0–7.9 kg with 1.0 mg, vs a 1.5 kg increase to 3.7 kg decrease with comparators. All subjects, in SUSTAIN 1–5, had a significant reduction in mean BW with semaglutide vs comparators (p<0.05) (Figure). There were greater BW reductions with semaglutide 1.0 vs 0.5 mg or comparators. Higher baseline BMI was associated with higher absolute weight loss with semaglutide. In the baseline BMI ≥35 kg/m2 subgroup, a ≥5% BW loss was achieved by 30–49% of subjects on semaglutide 0.5 mg, 47–68% on 1.0 mg, vs 6–27% on comparators; 5–12% and 11–23% vs 3–8% achieved ≥10% BW loss, respectively. There were no new safety or tolerability issues in the SUSTAIN trials. Semaglutide consistently had greater efficacy in reducing BW vs comparators, regardless of baseline BMI.

Starch Digestion-Related Amylase Genetic Variant Affects 2-Year Changes in Adiposity in Response to Weight-Loss Diets: The POUNDS Lost Trial.

Salivary and pancreatic amylases (encoded by AMY1 and AMY2 genes, respectively) are responsible for digesting starchy foods. AMY1 and AMY2 show copy number variations that affect differences in amylase amount and activity, and AMY1 copies have been associated with adiposity. We investigated whether genetic variants determining amylase gene copies are associated with 2-year changes in adiposity among 692 overweight and obese individuals who were randomly assigned to diets varying in macronutrient content. We found that changes in body weight (BW) and waist circumference (WC) were significantly different according to the AMY1-AMY2 rs11185098 genotype. Individuals carrying the A allele (indicating higher amylase amount and activity) showed a greater reduction in BW and WC at 6, 12, 18, and 24 months than those without the A allele (P < 0.05 for all). The association was stronger for long-term changes compared with short-term changes of these outcomes. The genetic effects on these outcomes did not significantly differ across diet groups. In conclusion, the genetic variant determining starch metabolism influences the response to weight-loss dietary intervention. Overweight and obese individuals carrying the AMY1-AMY2 rs11185098 genotype associated with higher amylase activity may have greater loss of adiposity during low-calorie diet interventions.

Effect of orlistat on plasma lipids and body weight: A systematic review and meta-analysis of 33 randomized controlled trials

Orlistat, an inhibitor of intestinal lipase, promotes body weight reduction. The lipid-lowering efficacy of orlistat is controversial and the effect of orlistat-induced body weight reduction on lipid changes has not been explored in meta-regression analyses. A systematic literature search was conducted to identify randomized controlled trials investigating the efficacy of orlistat on plasma total, low-density lipoprotein and high-density lipoprotein cholesterol, triglycerides and lipoprotein(a) levels. Thirty-three studies were included in the meta-analysis (5522 and 4210 participants in the orlistat therapy and control groups, respectively). Orlistat reduced body weight (weighted mean difference: −2.12, p <0.001), total-cholesterol (weighted mean difference: −0.30mmol/L, p <0.001), low-density lipoprotein cholesterol (weighted mean difference: −0.27mmol/L, p <0.001), high-density lipoprotein cholesterol (weighted mean difference: −0.034mmol/L, p <0.001) and triglyceride (weighted mean difference: −0.09mmol/L, p <0.001) concentrations, while no effect on lipoprotein(a) was observed. Total- and low-density lipoprotein cholesterol-lowering were associated negatively with duration of orlistat treatment and positively with body weight changes. In conclusion, Orlistat treatment slightly reduces cholesterol and triglyceride levels, but not lipoprotein(a) levels. Total- and low-density lipoprotein cholesterol levels reductions are more consistent in patients with greater body weight reduction and shorter duration of orlistat treatment.

Abstract P223: Starch Digestion Related Amylase Genotypes Affect 2-year Adiposity Changes in Response to Weight-loss Diets: The Pounds Lost Trial

Background/Aim: Salivary amylase, which is encoded by the salivary gene ( AMY1 ), is responsible for digesting starchy foods into sugar, and the AMY1 shows extensive copy number variations which directly affect differences in salivary and serum amylase amount and activity. Recent evidence suggests associations of low serum amylase levels and obesity. We investigated whether the copy number related AMY1 genotypes were associated with 2-year changes of adiposity in response to weight-loss diet intervention. Methods: This study included 692 obese individuals with data on AMY1 variant rs11185098 who were randomly assigned to 1 of 4 diets varying in macronutrient contents. Changes of body weight (BW) and waist circumference (WC) over 2 years during the intervention were evaluated according to the genotype. Results: We found that changes in BW and WC were significantly different according to the AMY1 genotype (Figure). After adjustment for age, sex, ethnicity, diet groups and value for the respective outcome traits at baseline, carrying the minor A allele (which indicates higher amylase amount and activity-associated allele) of rs11185098 was significantly associated with greater reduction of BW at 6, 12, 18, and 24 months (β (SE), p value; -0.7 (0.35), 0.04; -1.21 (0.46), 0.009; -1.63 (0.52), 0.0017; -1.27 (0.49), 0.0095, respectively). Also, increasing number of allele A was associated with a greater decrease of WC at 6, 12, 18 and 24 months (p &lt;0.05 for all). The genetic effects on these outcomes did not significantly differ across the diet groups. Conclusions: Our study indicated that the genetic variant responsible for starch metabolism significantly influenced on the response to weight-loss dietary intervention. Obese individuals carrying the AMY1 genotype that associated with higher salivary amylase activity may benefit from greater weight loss and the improvement of central adiposity in response to low-calorie diet interventions.

The Influence of a Meal Replacement Formula on Leptin Regulation in Obese Adults

Background and Purpose: The increasing prevalence of overweight and obese adults warrants improved dietary strategies for weight management and metabolic control. Hence, the objective of this study was to investigate the effects of a high-protein diet on leptin regulation. Methods: This study was a secondary analysis of data collected from a randomized controlled trial, conducted in 90 overweight adults (age: 47.5 ± 7.5 yrs.; BMI: 31.5 ± 2.3 kg/m2) who were followed over a 24-week control period. Changes in leptin levels were quantified to determine the influence of age, gender, leptin baseline levels, weight loss and intervention type. Participants were randomized into 3 interventions groups: 1) therapeutic lifestyle changes, (LS); 2) standardized meal replacement (Almased®) (MR); and 3) standardized meal replacement accompanied by supervised physical training (MRPT). For the analyses, both diet groups (MR, MRPT) were pooled into one common group and compared to the LS group in a parallel two-group study design with endpoint assessment after 24 weeks of intervention. Results: In total, 83 participants completed the 24-week study. Significant improvements in body composition and metabolic regulation occurred in all intervention participants regardless of their group assignment (LS; MR, MRPT). Participants’ consumption of the meal replacement (MR; MRPT) had an independent, significant effect on serum leptin levels (-15.5 ± 7.5 and -12.5 ± 7.8 vs. -8.7 ± 6.1 ng/ml). Greater body weight reductions were also observed in the diet groups (-8.9 ± 3.9 kg) compared to the LS group (-6.2 ± 4.2 kg). Conclusions: Our findings suggest that meal replacement can safely and effectively produce significant weight loss, which may be in part due to a reduction in plasma leptin levels. ClinicalTrials.gov Identifier: NCT00356785

Obesity treatment by very low-calorie-ketogenic diet at two years: reduction in visceral fat and on the burden of disease.

The long-term effect of therapeutic diets in obesity treatment is a challenge at present. The current study aimed to evaluate the long-term effect of a very low-calorie-ketogenic (VLCK) diet on excess adiposity. Especial focus was set on visceral fat mass, and the impact on the individual burden of disease. A group of obese patients (n = 45) were randomly allocated in two groups: either the very low-calorie-ketogenic diet group (n = 22), or a standard low-calorie diet group; (n = 23). Both groups received external support. Adiposity parameters and the cumulative number of months of successful weight loss (5 or 10 %) over a 24-month period were quantified. The very low-calorie-ketogenic diet induced less than 2 months of mild ketosis and significant effects on body weight at 6, 12, and 24 months. At 24 months, a trend to regress to baseline levels was observed; however, the very low-calorie-ketogenic diet induced a greater reduction in body weight (-12.5 kg), waist circumference (-11.6 cm), and body fat mass (-8.8 kg) than the low-calorie diet (-4.4 kg, -4.1 cm, and -3.8 kg, respectively; p < 0.001). Interestingly, a selective reduction in visceral fat measured by a specific software of dual-energy x-ray absorptiometry (DEXA)-scan (-600 g vs. -202 g; p < 0.001) was observed. Moreover, the very low-calorie-ketogenic diet group experienced a reduction in the individual burden of obesity because reduction in disease duration. Very low-calorie-ketogenic diet patients were 500 months with 5 % weight lost vs. the low-calorie diet group (350 months; p < 0.001). In conclusion, a very low-calorie-ketogenic diet was effective 24 months later, with a decrease in visceral adipose tissue and a reduction in the individual burden of disease.