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Background Extended-release naltrexone/bupropion (NB) is indicated for chronic weight management. Incretin agents are recommended for patients with type 2 diabetes. This analysis looked at the add-on of NB to incretins to see if weight loss could occur in patients already stabilized on incretin agents. Methods This was a post-hoc analysis of NB vs. placebo (PL) among subjects with type 2 diabetes stable on an incretin agent prior to randomization in a double-blind, PL-controlled cardiovascular outcome trial (N = 1317). Results Over 1 year, mean weight loss was significantly greater among NB patients vs. PL among those taking DPP-4i (mean absolute difference 4.6% [p p Conclusion NB appears to be effective in reducing weight in patients with T2DM and obesity/overweight who are taking DPP-4ihibitors or GLP-1RA. The SAE rates in all arms of this analysis were lower than have been reported in other cardiovascular outcome trials in type 2 diabetes. more...

Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed.In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions.The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]).In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935). more...

In the approval process for new weight management therapies, regulators typically require estimates of effect size. Usually, as with other drug evaluations, the placebo-adjusted treatment effect (i.e., the difference between weight losses with pharmacotherapy and placebo, when given as an adjunct to lifestyle intervention) is provided from data in randomized clinical trials (RCTs). At first glance, this may seem appropriate and straightforward. However, weight loss is not a simple direct drug effect, but is also mediated by other factors such as changes in diet and physical activity. Interpreting observed differences between treatment arms in weight management RCTs can be challenging; intercurrent events that occur after treatment initiation may affect the interpretation of results at the end of treatment. Utilizing estimands helps to address these uncertainties and improve transparency in clinical trial reporting by better matching the treatment-effect estimates to the scientific and/or clinical questions of interest. Estimands aim to provide an indication of trial outcomes that might be expected in the same patients under different conditions. This article reviews how intercurrent events during weight management trials can influence placebo-adjusted treatment effects, depending on how they are accounted for and how missing data are handled. The most appropriate method for statistical analysis is also discussed, including assessment of the last observation carried forward approach, and more recent methods, such as multiple imputation and mixed models for repeated measures. The use of each of these approaches, and that of estimands, is discussed in the context of the SCALE phase 3a and 3b RCTs evaluating the effect of liraglutide 3.0 mg for the treatment of obesity. more...

POINTS CLES L’obesite est une maladie chronique complexe dans laquelle la graisse corporelle anormale ou excessive (adiposite) nuit a la sante, augmente le risque de complications medicales a long terme et reduit la duree de vie[1][1]. Les etudes epidemiologiques definissent l’obe more...

KEY POINTS Obesity is a complex chronic disease in which abnormal or excess body fat (adiposity) impairs health, increases the risk of long-term medical complications and reduces lifespan.[1][1] Epidemiologic studies define obesity using the body mass index (BMI; weight/height2), which can stratify more...

Soluble fibre beneficially affects metabolism but whether it can augment the reductions in glycemia induced through intensive weight management has not been extensively studied. Our objective was to examine the adjunct effect of the soluble viscous fibre PGX® on glycemic control in adults with type 2 diabetes (T2D) enrolled in a year-long medically supervised weight management program. In a placebo-controlled, double-blind study, 290 adults with overweight/obesity and T2D were randomized to receive PGX (15–20 g/day) or isocaloric placebo (rice flour, 6.4–8.6 g/day) as an adjunct to intensive weight management for 52 weeks. The primary outcome was change in glycemic control (HbA1c). Other outcome measures included weight loss, blood lipids, blood pressure, cytokines and fecal microbiota. Compared to baseline HbA1c in PGX (7.2 ± 1.1%) and placebo (7.0 ± 0.9%) groups, there was a significant reduction at 16 and 26 weeks, however, only PGX showed a significant absolute reduction of 0.23% at 52 weeks; there were no between-group differences in HbA1c. At 52 weeks, only PGX significantly decreased body weight compared to baseline and reduced waist circumference at all time points. Compared to baseline, only PGX showed a significant reduction in LDL cholesterol at 16 and 26 weeks. PGX significantly increased the relative abundance of Collinsella, Parabacteroides and Roseburia. Adding PGX to a weight management program for individuals with T2D provides a sustained reduction in HbA1c compared to placebo. Improvements in other metabolic outcomes suggest that PGX may be a promising adjunct to weight loss programs in patients with T2D. This trial was registered at ClinicalTrials.gov as NCT01644201. more...

Summary Objective Liraglutide 3.0 mg is associated with clinically significant weight loss in clinical trials, but real‐world data are lacking. In this analysis, weight loss and persistence outcomes with liraglutide 3.0 mg were assessed across obesity classes, in a real‐world clinical setting. Methods Secondary analysis of an observational, retrospective study of liraglutide 3.0 mg for weight management (as adjunct to diet and exercise) at six Wharton Medical Clinics in Canada. Patients were categorized by body mass index (BMI, kg/m2) into obesity class I (BMI 30–34.9); class II (BMI 35–39.9); and class III (BMI ≥40). Change in weight, categorical weight loss, time to maintenance dose (defined as the time to reach the full liraglutide 3.0 mg maintenance dose) and persistence were assessed for each class and for differences between classes. Results Of 308 patients, 70 (22.7%) had obesity class I, 83 (26.9%) obesity class II and 155 (50.3%) obesity class III. Similar percentage change in weight was observed between obesity classes (mean [standard deviation, SD]: −7.0% [6.0], −6.6% [6.0] and −6.1% [5.0], respectively; p = .640), and similar proportions achieved ≥5% weight loss (60.4%, 62.0% and 55.3%, respectively; p = .717) at 6 months. Mean time to maintenance dose (SD) was 64.2 (56.4) d, 76.4 (56.3) d and 71.4 (54.5) d for obesity classes I, II and III, respectively (p = .509). Persistence with medication was also similar between obesity classes (p = .358). Conclusions These findings suggest that real‐world treatment with liraglutide 3.0 mg, regardless of obesity class, is associated with similar clinically significant weight loss, time to maintenance dose and medication persistence. more...

AIM We evaluated gastrointestinal (GI) adverse events (AEs) with once-weekly semaglutide 2.4 mg in adults with overweight or obesity and their contribution to weight loss (WL). MATERIALS AND METHODS AE analyses pooled data from the Semaglutide Treatment Effect in People With Obesity (STEP) 1-3 trials for participants randomized to 68 weeks of semaglutide 2.4 mg (n = 2117) or placebo (n = 1262). WL was analysed by presence/absence of GI AEs. Mediation analysis estimated WL effects mediated by and unrelated to GI AEs. GI tolerability with semaglutide 2.4 mg maintenance and cessation after dose escalation was evaluated using STEP 4 data among 803 participants tolerating 20 weeks of semaglutide run-in. RESULTS GI AEs were more common with semaglutide 2.4 mg than placebo, with most frequently nausea (43.9% vs. 16.1% of participants), diarrhoea (29.7% vs. 15.9%), vomiting (24.5% vs. 6.3%) and constipation (24.2% vs. 11.1%). Most GI AEs with semaglutide were non-serious (99.5% of AEs), mild-to-moderate (98.1%), transient and occurred most frequently during/shortly after dose escalation. Few semaglutide-treated participants (4.3%) permanently discontinued treatment for GI AEs. In STEP 1-3, mean WL with semaglutide 2.4 mg was similar in participants without (9.6%-17.1%) versus with GI AEs (11.4%-17.7%). Consistent with this observation, mediation analysis found that GI AEs contributed little to semaglutide-induced WL: of the additional 7.6%-14.4% WL with semaglutide versus placebo more...

Objective This study aimed to compare weight loss (WL) outcomes for patients taking antidepressants and/or antipsychotics with those not taking psychiatric medication. Methods A total of 17,519 adults enrolled in a lifestyle WL intervention at the Wharton Medical Clinics in Ontario, Canada, were analyzed. Sex-stratified multivariable linear regression analysis was used to examine the association of taking antidepressants, antipsychotics, both, or neither with WL when adjusting for age, initial weight, and treatment time. Results Twenty-three percent of patients were taking at least one psychiatric medication. Patients lost a significant amount of weight (P 0.05). Conversely, men taking antidepressants lost only slightly less weight than men taking both classes or neither class of psychiatric medication (3.2 ± 0.3 kg vs. 5.6 ± 0.9 kg and 4.3 ± 0.1 kg; P 0.05). Conclusions Results of this study suggest that those who participate in a weight management program can lose significant amounts of weight regardless of psychiatric medication use. more...

OBJECTIVES: Intermittent fasting (IF) is a popular trending diet, yet there is limited evidence-based support considering its clinical impact on cardiometabolic outcomes. In an effort to inform the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy, we conducted a network meta-analysis of randomized controlled trials (RCTs) comparing IF strategies and continuous energy restriction (CER) on cardiometabolic outcomes using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched through Nov 2020. We included RCTs assessing the effect of IF strategies (alternate-day fasting (ADF), whole-day periodic fasting (WDF), time-restricted feeding (TRF)), CER, and ad libitum diet. Outcomes included body weight, fasting glucose and LDL-cholesterol. Two independent researchers extracted data and assessed risk of bias. A network meta-analysis was performed and data were expressed as mean differences (MD) with 95% confidence intervals (CI). The certainty of the evidence was assessed using GRADE. RESULTS: We identified 19 RCTs (n = 590) including adults of varying health backgrounds. ADF and CER both showed a benefit for body weight reduction compared to ad libitum diet (18 trials, n = 520; MD −3.95 kg [95% CI −6.09, −1.81] and MD −2.85 kg [95% CI −4.99, −0.71], respectively). For fasting glucose (17 trials, n = 590), TRF showed a benefit compared to ad libitum diet (MD −0.39 mmol/L [95% CI −0.59, −0.20]), to CER (MD −0.25 mmol/L [95% CI, −0.45 to −0.06]) and to WDF (MD −0.20 mmol/L [95% CI, −0.45, −0.05]). Furthermore, ADF showed a benefit in reducing LDL-cholesterol (17 trials, n = 590) compared to ad libitum diet (MD −0.21 mmol/L [95% CI −0.40, −0.1]), and to CER (MD −0.15 mmol/L [95% CI −0.31, −0.01]). The certainty of the evidence ranged from high to moderate due to variable downgrades for imprecision. CONCLUSIONS: Current evidence provides a good indication that IF strategies have similar benefits to CER for weight loss but may have additional benefits for fasting glucose and LDL-cholesterol. Long-term high quality RCTs are needed to clarify the effect of different IF strategies on cardiometabolic outcomes. FUNDING SOURCES: Diabetes and Nutrition Study Group of the EASD, Canadian Institutes of Health Research (CIHR), Diabetes Canada. more...

An analysis of the STEP 2 trial evaluated the effect of s.c. semaglutide 2.4 mg vs. placebo (PBO) on physical function (PF) in adults with overweight/obesity and type 2 diabetes (T2D). The STEP 2 trial was an RCT in adults with BMI ≥27 kg/m2 and T2D (NCT03552757). Patients were randomized 1:1:1 to 68 weeks’ once-weekly semaglutide 2.4 mg (N=404), 1.0 mg (N=403; data not shown), or PBO (N=403), plus lifestyle changes. Endpoints included change in PF (baseline-week 68) using the SF-36v2® Health Survey acute version (SF-36) and Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQoL-Lite-CT), and achievement of meaningful within-person PF improvements (≥3.7 points [SF‑36]; ≥14.6 points [IWQoL-Lite-CT]). Patients were 51% female, with a mean age of 55 years, body weight 99.8 kg, and BMI 35.7 kg/m2. Body weight change at week 68 with semaglutide 2.4 mg vs. PBO was -9.6% vs. -3.4%. Semaglutide significantly improved PF vs. PBO on SF-36 and IWQoL‑Lite‑CT (Table). SF-36 and IWQoL-Lite-CT PF improvements correlated with weight loss during the trial. Proportions of patients with clinically meaningful PF improvements were greater with semaglutide vs. PBO (Table). In adults with overweight/obesity and T2D, semaglutide 2.4 mg improved PF vs. PBO, and led to greater proportions of patients with clinically meaningful PF changes in SF-36 and IWQoL-Lite-CT. Disclosure S. Wharton: Advisory Panel; Self; Novo Nordisk A/S, Novo Nordisk Canada Inc., Speaker’s Bureau; Self; AstraZeneca, Bausch Health, Canada, Novo Nordisk, Novo Nordisk Canada Inc. H. H. Meincke: Employee; Self; Novo Nordisk A/S. R. F. Kushner: Advisory Panel; Self; Novo Nordisk A/S. T. Kalayci oral: Employee; Self; Novo Nordisk A/S. S. Pedersen: Advisory Panel; Self; AstraZeneca, Bausch and Lomb Incorporated, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Global Services, LLC., Novo Nordisk, Consultant; Self; Abbott, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Speaker’s Bureau; Self; Abbott Laboratories, AstraZeneca, Bausch and Lomb Incorporated, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi. D. Rubino: Advisory Panel; Self; Novo Nordisk, Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk, Speaker’s Bureau; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. D. H. Ryan: Advisory Panel; Self; Alyvent, Naturally Slim, Epitommee,, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Global Services, LLC., Pfizer Inc., Redesign Health, Inc., Sanofi, Consultant; Self; Bausch Health, Canada, Phenomix, Xeno Bioscience, Gila Therapeutics, Scientific Intake, UnitedHealth Group, Other Relationship; Self; Novo Nordisk Inc. N. Zeuthen: Employee; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. R. Kolotkin: Consultant; Self; Novo Nordisk, Other Relationship; Self; Rhythm Pharmaceuticals, Inc. Funding Novo Nordisk A/S more...

Effects of s.c. semaglutide 2.4 mg vs. placebo on health-related quality of life (HRQoL) were evaluated in the STEP 2 trial in adults with overweight/obesity and T2D. The STEP 2 trial was an RCT in adults with BMI ≥27 kg/m2 and T2D (NCT03552757). Patients were randomized 1:1:1 to 68 weeks’ once-weekly semaglutide 2.4 mg (N=404), 1.0 mg (N=403; results not shown), or placebo (N=403), plus lifestyle intervention. Changes in scores at week 68, and achievement of clinically meaningful within-person improvements (see Table for meaningful change thresholds), in weight-related QoL (Impact of Weight on Quality of Life-Lite Clinical Trials Version [IWQoL-Lite-CT]) and HRQoL (SF-36v2® Health Survey acute version [SF-36]) were assessed. Body weight change at week 68 with semaglutide 2.4 mg vs. placebo was -9.6% vs. -3.4%. Changes in IWQoL-Lite-CT scores and SF-36 scores (except role-emotional) were consistently in favor of semaglutide vs. placebo (Table). The proportions of patients with clinically meaningful improvements was greater with semaglutide vs. placebo for all IWQoL-Lite-CT scores and SF-36 physical functioning score (Table). In adults with overweight/obesity and T2D, semaglutide 2.4 mg improved both physical and mental health components vs. placebo and led to greater proportions of patients with clinically meaningful changes in weight-related QoL and physical functioning. Disclosure D. Rubino: Advisory Panel; Self; Novo Nordisk, Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk, Speaker’s Bureau; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. L. Faerch: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. H. H. Meincke: Employee; Self; Novo Nordisk A/S. R. F. Kushner: Advisory Panel; Self; Novo Nordisk A/S. S. Pedersen: Advisory Panel; Self; AstraZeneca, Bausch and Lomb Incorporated, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Global Services, LLC., Novo Nordisk, Consultant; Self; Abbott, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Speaker’s Bureau; Self; Abbott Laboratories, AstraZeneca, Bausch and Lomb Incorporated, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi. D. H. Ryan: Advisory Panel; Self; Alyvent, Naturally Slim, Epitommee,, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Global Services, LLC., Pfizer Inc., Redesign Health, Inc., Sanofi, Consultant; Self; Bausch Health, Canada, Phenomix, Xeno Bioscience, Gila Therapeutics, Scientific Intake, UnitedHealth Group, Other Relationship; Self; Novo Nordisk Inc. S. Wharton: Advisory Panel; Self; Novo Nordisk A/S, Novo Nordisk Canada Inc., Speaker’s Bureau; Self; AstraZeneca, Bausch Health, Canada, Novo Nordisk, Novo Nordisk Canada Inc. N. Zeuthen: Employee; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. R. Kolotkin: Consultant; Self; Novo Nordisk, Other Relationship; Self; Rhythm Pharmaceuticals, Inc. Funding Novo Nordisk A/S more...

The weight loss history and weight loss goals were examined in 4108 patients referred to a publicly funded evidence-based clinical weight management program using a retrospective chart review. The majority of patients were white females, aged of 50.1 ± 13.7 years and a BMI of 39.0 ± 7.5 kg/m2 . Pregnancy was the most common reason for weight gain in women (17.7%) and while the reasons in men are more varied (injury, stress and medication: all ~5%). Over 50% of patients cited no specific reason for their weight gain. Self-directed diet and exercise were the most commonly used self-reported weight loss methods. Women were more likely to report using medication and bariatric surgical weight loss methods than men (P more...

Objective The obesity epidemic is a public health concern, warranting further research into pharmacological treatments for weight management (WM) as an adjunct to lifestyle interventions. The Semaglutide Treatment Effect in People with obesity (STEP) program aims to investigate the effect of semaglutide versus placebo on weight loss, safety, and tolerability in adults with obesity or overweight. Methods Across five phase 3 trials (NCT03548935, WM; NCT03552757, WM in type 2 diabetes; NCT03611582, WM with intensive behavioral therapy; NCT03548987, sustained WM; and NCT03693430, long-term WM), ~5,000 participants are being randomly assigned to receive semaglutide 2.4 mg once weekly subcutaneously versus placebo. Results will be available in 2020/2021. For all trials, the primary end point is change from baseline to end of treatment in body weight. Results Participants have a mean age of 46.2 to 55.3 years, are mostly female (mean: 74.1%-81.0%), and have a mean BMI of 35.7 to 38.5 kg/m2 and a mean waist circumference of 113.0 to 115.7 cm. Conclusions The STEP program evaluates the efficacy and safety of semaglutide 2.4 mg subcutaneously once weekly in a broad population. The trials will provide insights on WM in people with obesity with and without type 2 diabetes and on long-term follow-up. more...

There is significant overlap between obesity and type 2 diabetes (T2DM). Incretin agents (dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs)) are recommended as second-line to metformin in patients with T2DM due to their glucose-lowering effects, low risk of hypoglycemia, and favorable effect on weight. Naltrexone/bupropion (NB) is a combination therapy approved in North America and Europe for chronic weight management. This is an exploratory analysis of the efficacy and safety of NB in T2DM subjects enrolled in two double-blind, placebo-controlled Phase III studies (N=1344), that were stable on an incretin agent prior to randomization. At 1 year, mean weight change was -4.6% ± 0.21% in NB (N=700) compared to -1.1% ± 0.15% in placebo (N=644). In subjects randomized to NB that achieved at ≥5% weight loss at week 16 (early responders, N=269), mean weight change at 1 year was -8.8% ± 0.34%. An analysis of covariance using LOCF adjusting for age, sex, baseline BMI, baseline weight, and responder status revealed no significant interaction between incretin agent and weight treatment medication (p=0.1317), a significant treatment NB vs. placebo effect (p In conclusion, NB is efficacious and safe in reducing weight in patients with obesity and T2DM on DPP-4 inhibitors and GLP-1RAs, and may be an effective addition when weight loss is a focus in treatment. Disclosure S. Wharton: Advisory Panel; Self; Bausch Health Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. P. Yin: Employee; Self; Bausch Health. F. Camacho: Consultant; Self; Bausch + Lomb, Janssen Pharmaceuticals, Inc. M. Burrows: Employee; Self; Bausch Health. J. Blavignac: Employee; Self; Bausch Health Canada. M. Barakat: Employee; Self; Bausch Health. more...

Background The cause of the obesity epidemic is multifactorial, but may, in part, be related to medication-induced weight gain. While clinicians may strive to do their best to select pharmacotherapy(ies) that has the least negative impact on weight, the literature regarding the weight effects of medication is often limited and devoid of alternative therapies. Results Antipsychotics, antidepressants, antihyperglycemics, antihypertensives and corticosteroids all contain medications that were associated with significant weight gain. However, there are several medication alternatives within the majority of these classes associated with weight neutral or even weight loss effects. Further, while not all of the classes of medication examined in this review have weight-favorable alternatives, there exist many other tools to mitigate weight gain associated with medication use, such as changes in dosing, medication delivery or the use of adjunctive therapies. Conclusion Medication-induced weight gain can be frustrating for both the patient and the clinician. As the use of pharmaceuticals continues to increase, it is pertinent for clinicians to consider the weight effects of medications prior to prescribing or in the course of treatment. In the case where it is not feasible to make changes to medication, adjunctive therapies should be considered. more...

Background Obesity is a major public health issue, and new pharmaceuticals for weight management are needed. Therefore, we evaluated the efficacy and safety of the glucagon-like peptide-1 (GLP-1) analogue semaglutide in comparison with liraglutide and a placebo in promoting weight loss. Methods We did a randomised, double-blind, placebo and active controlled, multicentre, dose-ranging, phase 2 trial. The study was done in eight countries involving 71 clinical sites. Eligible participants were adults (≥18 years) without diabetes and with a body-mass index (BMI) of 30 kg/m 2 or more. We randomly assigned participants (6:1) to each active treatment group (ie, semaglutide [0·05 mg, 0·1 mg, 0·2 mg, 0·3 mg, or 0·4 mg; initiated at 0·05 mg per day and incrementally escalated every 4 weeks] or liraglutide [3·0 mg; initiated at 0·6 mg per day and escalated by 0·6 mg per week]) or matching placebo group (equal injection volume and escalation schedule to active treatment group) using a block size of 56. All treatment doses were delivered once-daily via subcutaneous injections. Participants and investigators were masked to the assigned study treatment but not the target dose. The primary endpoint was percentage weight loss at week 52. The primary analysis was done using intention-to-treat ANCOVA estimation with missing data derived from the placebo pool. This study is registered with ClinicalTrials.gov, number NCT02453711. Findings Between Oct 1, 2015, and Feb 11, 2016, 957 individuals were randomly assigned (102–103 participants per active treatment group and 136 in the pooled placebo group). Mean baseline characteristics included age 47 years, bodyweight 111·5 kg, and BMI 39·3 kg/m 2. Bodyweight data were available for 891 (93%) of 957 participants at week 52. Estimated mean weight loss was −2·3% for the placebo group versus −6·0% (0·05 mg), −8·6% (0·1 mg), −11·6% (0·2 mg), −11·2% (0·3 mg), and −13·8% (0·4 mg) for the semaglutide groups. All semaglutide groups versus placebo were significant (unadjusted p≤0·0010), and remained significant after adjustment for multiple testing (p≤0·0055). Mean bodyweight reductions for 0·2 mg or more of semaglutide versus liraglutide were all significant (−13·8% to −11·2% vs −7·8%). Estimated weight loss of 10% or more occurred in 10% of participants receiving placebo compared with 37–65% receiving 0·1 mg or more of semaglutide (p more...

The aim of this study was to examine the associations between baseline and changes in resting metabolic rate (RMR) with chronic condition(s) and weight loss (WL). Sex stratified analysis was undertaken on 393 adults from the Wharton Weight Management Clinics. The association between baseline RMR and WL was examined adjusting for age, BMI, ethnicity and treatment time. The association between changes in RMR (ΔRMR) and WL was also examined adjusting for baseline RMR and above covariates. Models were further adjusted for high glucose, triglycerides, blood pressure, low-density lipoprotein (LDL) and low high-density lipoprotein (HDL). While men (6.0 ± 8.6 kg) and women (5.6 ± 8.3 kg) had significant WL throughout the intervention, their measured decreases in RMR (-48 ± 322 kcal and -5 ± 322 kcal, respectively) were non-significant (P > 0.05). Individuals with a high blood pressure had a higher baseline RMR and women with a high LDL had a lower baseline RMR than those without the chronic condition (P 0.05) in both models. Participants with a low baseline RMR do not appear to be at a disadvantage for WL. Further, WL can occur without decreases in RMR in populations with high levels of obesity and obesity-related comorbidities. more...

Summary Objective Weight management medications can significantly increase patients' chances of achieving a clinically meaningful weight loss if patients persist with treatment. This retrospective observational study of de‐identified medical records of 311 patients is the first real‐world study examining persistence with liraglutide 3.0 mg in Canada, and also investigates associations between the SaxendaCare® patient support program and persistence and weight loss. Methods Overall persistence was assessed, as well as associations of enrollment in SaxendaCare®, persistence and weight loss. Results Overall mean (standard deviation) persistence with liraglutide 3.0 mg was 6.3 (4.1) months, and 67.5% (n = 210) and 53.7% (n = 167) of patients persisted for ≥4 and ≥ 6 months, respectively. Enrollment in SaxendaCare® was associated with significantly longer persistence with liraglutide 3.0 mg and greater weight loss. Patients enrolled in SaxendaCare® (n = 119) persisted for 7.9 (4.0) versus 5.2 (3.8) months for those not enrolled (n = 184) (p < 0.001), and had significantly greater percent weight loss after 6 months regardless of the duration of their persistence (−7.9% vs −5.5% from baseline, p < 0.01). Conclusions These findings suggest that, in clinical settings, persistence with liraglutide 3.0 mg can exceed 6 months, and that enrolling in SaxendaCare® may be associated with comparatively longer persistence and, regardless of persistence, greater weight loss. more...

Summary To assess the effectiveness of liraglutide 3.0 mg in post‐bariatric surgery patients, and to determine whether this would differ based on the type of bariatric surgery. One hundred seventeen post‐bariatric surgery patients from the Wharton Medical Clinic were analysed. Changes in weight while taking liraglutide 3.0 mg were examined for all patients, and by three types of bariatric surgery—Roux‐en‐Y gastric bypass, gastric banding and gastric sleeve. Patients primarily underwent Roux‐en‐Y gastric bypass (n = 53, 45.3%) or gastric banding (n = 50, 42.7%). Over 7.6 ± 7.1 months taking liraglutide 3.0 mg, patients lost a statistically significant amount of weight (−6.3 ± 7.7 kg, P .05). This decrease in weight remained significant after 1‐year of taking liraglutide 3.0 mg (P more...

The prevalence of obesity has been increasing globally. Due to the negative health effects, obesity has been recognized as a major public health concern. Obesity is defined as a body mass index (BMI) of greater than or equal to 30 kg/m2. The location (i.e., abdominal) and type of excess weight contribute to ill-health; thus methods such as waist circumference and body fat measurements are used in the assessment of obesity. In relation to obesity and type 2 diabetes (T2D), genetics, physical activity, and diet are key predictors to the development of these chronic conditions. Fortunately, treatment options for obesity and T2D are similar and can be categorized as lifestyle, pharmacological, or surgical. When medications or surgery is added to lifestyle interventions, there is much greater benefit in terms of weight loss and diabetes control over lifestyle interventions on their own. more...

Objective: To systematically review the literature on weight management pharmaceutical use in patients who have had bariatric surgery. Methods: Google Scholar, Pubmed, Cochrane, Embase, Web of Science, and Clinical Trials were searched from inception to December 31st, 2018 inclusive. Results: Thirteen studies met inclusion and reported decreases in weight with the use of weight management medications in post-bariatric surgical patients. Five studies examined weight loss outcomes by the type of bariatric surgery procedure, and four of these studies observed less weight loss in patients who had undergone gastric sleeve compared to those who had roux-en-y bypass (n = 3 papers) and adjustable gastric banding (n = 1 paper) with medication use. Four studies compared the effectiveness of medications for weight management and observed slightly greater weight loss with the use of topiramate and phentermine as a monotherapy compared to other weight loss medications. Using a sub-sample of participants, authors observed less weight loss on metformin but not phentermine or topiramate for younger adults. Another post-hoc analysis in the same sample observed greater weight loss for older adults with liraglutide 1.8mg. Side effects were reported in seven studies and were overall consistent with those previously reported in non-surgical populations. Conclusions: Results of this systematic review suggest pharmacotherapy may be an effective tool as an adjunct to diet and physical activity to support weight loss in post-bariatric surgery patients. However, due to most studies lacking a control or placebo group, more rigorous research is required to determine the efficacy of this intervention. more...

Background: Despite the increasing global adverse health impact of obesity, there are few pharmacological options for effective weight management. STEP 1 investigated the efficacy and safety of the glucagon-like peptide-1 analogue, subcutaneous (s.c.) semaglutide, for weight management in adults with overweight or obesity. Methods: This randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 129 sites across 16 countries (NCT03548935). Adults aged ≥18 years with either body mass index (BMI) ≥30 kg/m2 or BMI ≥27 kg/m2 with ≥1 weight-related comorbidity, without type 2 diabetes, were randomized 2:1 to 68 weeks’ treatment with once-weekly s.c. semaglutide 2.4 mg or placebo, both as adjunct to lifestyle intervention. The co-primary endpoints were percentage change in body weight and achievement of weight loss ≥5%. Cardiometabolic risk factors, patient-reported outcomes, and safety/tolerability were also assessed. Two estimands were defined: treatment policy (effect regardless of treatment adherence and use of rescue intervention) and trial product (effect assuming treatment adherence and without rescue intervention); results are presented for the treatment policy estimand, unless stated otherwise. P values for parameters marked with # were not controlled for multiplicity. Results: 1961 randomized participants (mean age 46 years, body weight 105.3 kg, BMI 37.9 kg/m2; 74.1% female) were included. Mean body weight change from baseline to week 68 was −14.9% in the semaglutide group vs −2.4% with placebo (estimated treatment difference [ETD]: −12.4%; 95% confidence interval (CI): −13.4, −11.5; p Conclusion: In adults with overweight or obesity, once-weekly s.c. semaglutide 2.4 mg plus lifestyle intervention induced a mean weight loss of approximately 15% by week 68. Clinically beneficial weight loss of ≥10% was achieved by over two-thirds of participants and ≥20% by one-third of participants, along with associated improvements in cardiometabolic risk factors and physical functioning. more...

Approximately 1 in 4 adult Canadians are obese and, thus, are at an elevated risk for developing type 2 diabetes, cardiovascular disease and other conditions. Current treatment guidelines recommend that obese individuals lose 5% to 10% of their starting weights to minimize the risk factors for cardiovascular disease and reduce the risk for developing type 2 diabetes or hypertension. All obesity-management strategies involve lifestyle management, but few patients will lose a significant amount of weight and manage to keep it off over the long term using just this strategy. Bariatric surgery is associated with significant long-term weight loss but is restricted to subjects with very high body mass indices, who often wait many years to undergo the procedure. Recent breakthroughs in understanding the mechanisms underlying the development and maintenance of elevated body fat have led to the arrival of new obesity pharmacotherapies. These novel antiobesity therapies, which work by reducing energy intake or through increasing satiety, decreasing hunger, or reducing absorption of calories, may be used indefinitely once patients have demonstrated significant responses (usually defined as ≥5% weight loss) over the first 12 weeks of treatment. To date, 2 long-term obesity pharmacotherapies have been approved and are available in Canada: liraglutide and orlistat. Here, I summarize the mechanisms and clinical features of medications for long-term obesity management that are available in Canada, as well as those available in other jurisdictions or are currently in development. more...

Summary The objective of the study was to assess the interest, views and patient-perceived barriers to bariatric surgery among surgery-eligible patients. Surveys were completed at a weight management clinic and local hospital in Ontario, Canada. Patients were ≥18 years of age with a body mass index (BMI) >40 kg m−2 or BMI > 35 kg m−2 with ≥1 comorbidity. The sample included 105 participants, 73.3% female, with a mean BMI of 46.6 ± 7.1 kg m−2. Only 33.3% of participants were interested in surgery; 50.5% of participants were not interested and 16.2% had mixed feelings. Participants identified risks (69.5%) and side effects (57.1%) as significant surgical barriers. Interested participants were more likely to perceive themselves as obese, were unhappy with their current weight loss method and were less likely to fear surgery (P more...

Objective Real‐world clinical effectiveness of liraglutide 3.0 mg, in combination with diet and exercise, was investigated 4 and 6 months post initiation. Changes in absolute and percent body weight were examined from baseline. Methods A cohort of liraglutide 3.0 mg initiators in 2015 and 2016 was identified from six Canadian weight‐management clinics. Post initiation values at 4 and 6 months were compared with baseline values using a paired t test. Results The full cohort consisted of 311 participants, with 210 in the ≥ 4‐month persistence group and 167 in the ≥ 6‐month persistence group. Average baseline BMI was 40.7 kg/m2, and weight was 114.8 kg. There was a significant change in body weight 6 and 4 months after initiation of treatment in persistent subjects (≥ 6‐month: −8.0 kg, P 10% body weight, respectively. Conclusions In a real‐world setting, liraglutide 3.0 mg, when combined with diet and exercise, was associated with clinically meaningful weight loss. more...

KEY POINTS The Canadian Cardiovascular Harmonized National Guideline Endeavour (C-CHANGE) is a nationally endorsed guideline process, targeting primary care health care practitioners. The C-CHANGE guideline is a composite of nine of Canada’s cardiovascular-focused clinical practice guidelines ([ more...

Introduction. One in three US adults is living with obesity or hypertension, and more than 75% of hypertensive individuals are using antihypertensive medications. Therefore, it is important to examine blood pressure (BP) differences in populations that are using these medications with differing obesity status. Aim. We examined whether BP attained when using various antihypertensive medications varies amongst different body mass index (BMI) categories and whether antihypertensive medication use is associated with differences in other metabolic risk factors, independent of BMI. Methods. Adults with hypertension from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 were used (n=15,285). Linear regression analyses were used to examine the main effects and interaction between antihypertensive use and BMI. Results. In general, users of antihypertensive medications had lower BP than those not taking BP medications (NoBPMed) (P<0.05), whereby in women, the differences in systolic BP between angiotensin-converting-enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) users and NoBPMed were greater in those with obesity (ACE inhibitors: −14 ± 1 mmHg; ARB: −16 ± 1 mmHg) compared to normal weight individuals (ACE inhibitors: −9 ± 1 mmHg; ARB: −11 ± 1 mmHg) (P<0.05). Diastolic BP differences between women ARB users and NoBPMed were also greatest in obesity (−5 ± 1 mmHg) (P<0.05) whilst there were no differences in normal weight individuals (−1 ± 1 mmHg) (P>0.05). Furthermore, glucose levels and waist circumference in women were higher in those using ACE inhibitors compared to diuretics (P<0.05). Conclusion. ACE inhibitors and ARBs may be associated with more beneficial BP profiles in women with obesity, with no obesity-related BP differences for antihypertensive medication in men. However, there could be potential cardiometabolic effects for some antihypertensive medications that should be explored further. more...

Background Previous literature suggests the beneficial effects of fitness on abdominal obesity may be attenuated in obesity and abolished in severe obesity. It is unclear whether the beneficial association between fitness and health is similarly present in those with mild and severe obesity. Methods Patients from the Wharton Medical Clinic (n = 853) completed a clinical examination and maximal treadmill test. Patients were categorized into fit and unfit based on age- and sex-categories and body mass index (BMI) class (mild: ≤ 34.9 kg/m2, moderate: 35–39.9 kg/m2 or severe obesity: ≥ 40 kg/m2). Results Within the sample, 41% of participants with mild obesity had high fitness whereas only 25% and 11% of the participants with moderate and severe obesity, respectively, had high fitness. BMI category was independently associated with most of the metabolic risk factors, while fitness was only independently associated with systolic blood pressure and triglycerides (P more...

Sean Wharton,1,2 Jasmine Lee,1 Rebecca AG Christensen1 1The Wharton Medical Clinic, Hamilton, ON, Canada; 2School of Kinesiology and Health Science, York University, Toronto, ON, Canada Abstract: Current methods for the treatment of excess weight can involve healthy behavior changes, pharmacotherapy, and surgical interventions. Many individuals are able to lose some degree of weight through behavioral changes; however, they are often unable to maintain their weight loss long-term. This is in part due to physiological processes that cannot be addressed through behavioral changes alone. Bariatric surgery, which is the most successful treatment for excess weight to date, does result in physiological changes that can help with weight loss and weight maintenance. However, many patients either do not qualify or elect to not have this procedure. Fortunately, research has recently identified changes in neurochemicals (i.e., orexigens and anorexigens) that occur during weight loss and contribute to weight regain. The neurochemicals and hormones may be able to be targeted by medications to achieve greater and more sustained weight loss. Two medications are approved in adjunction to lifestyle management for weight loss in Canada: orlistat and liraglutide. Both medications are able to target physiological processes to help patients lose weight and maintain a greater amount of weight loss than with just behavioral modifications alone. Two other weight management medications, which also target specific physiological processes to aid in weight loss and its maintenance, a bupropion/naltrexone combination and lorcaserin, are currently pending approval in Canada. Nonetheless, there remain significant barriers for health care professionals to prescribe medications for weight loss, such as a lack of training and knowledge in the area of obesity. Until this has been addressed, and we begin treating obesity as we do other diseases, we are unlikely to combat the increasing trend of obesity in Canada and worldwide. Keywords: weight loss, pharmacological intervention, liraglutide, weight loss medication more...

Onestime que de 80 % a 90 %des personnes atteintes de diabete de type 2 ont un exces de poids ou sont obeses. Chez les personnes diabetiques, un indice demasse corporelle plus eleve est associe a unemortalite generale accrue. Une modeste perte de poids, soit de 5,0 % a 10,0 % par rapport au poids initial, peut entrainer une amelioration importante de la maitrise glycemique et des facteurs de risque cardiovasculaires. Chez les personnes diabetiques ou predisposees au diabete qui ont un exces de poids ou qui sont obeses, il faut mettre enœuvre un programme complet d’interventions axees sur un mode de vie sain visant a prevenir un gain de poids et a atteindre et maintenir un poids sante. Plusieurs classes d’antihyperglycemiants sont associees a un gain de poids, alors que d’autres n’exercent aucun effet sur le poids ou sont associes a une perte de poids. Il faut tenir compte des effets des medicaments sur le poids corporel dans la prise en charge de la glycemie. La chirurgie bariatrique peut etre envisagee chez certains patients quand d’autres interventions ne permettent pas d’atteindre les objectifs en matiere de perte de poids. more...

Liraglutide, a once-daily human glucagon-like peptide-1 analog, induced clinically meaningful weight loss in a phase 2 study in obese individuals without diabetes. The present randomized phase 3 trial assessed the efficacy of liraglutide in maintaining weight loss achieved with a low-calorie diet (LCD).Obese/overweight participants (≥18 years, body mass index ≥30 kg m(-2) or ≥27 kg m(-2) with comorbidities) who lost ≥5% of initial weight during a LCD run-in were randomly assigned to liraglutide 3.0 mg per day or placebo (subcutaneous administration) for 56 weeks. Diet and exercise counseling were provided throughout the trial. Co-primary end points were percentage weight change from randomization, the proportion of participants that maintained the initial ≥5% weight loss, and the proportion that lost ≥5% of randomization weight (intention-to-treat analysis). ClinicalTrials.gov identifier: NCT00781937.Participants (n=422) lost a mean 6.0% (s.d. 0.9) of screening weight during run-in. From randomization to week 56, weight decreased an additional mean 6.2% (s.d. 7.3) with liraglutide and 0.2% (s.d. 7.0) with placebo (estimated difference -6.1% (95% class intervals -7.5 to -4.6), P0.0001). More participants receiving liraglutide (81.4%) maintained the ≥5% run-in weight loss, compared with those receiving placebo (48.9%) (estimated odds ratio 4.8 (3.0; 7.7), P0.0001), and 50.5% versus 21.8% of participants lost ≥5% of randomization weight (estimated odds ratio 3.9 (2.4; 6.1), P0.0001). Liraglutide produced small but statistically significant improvements in several cardiometabolic risk factors compared with placebo. Gastrointestinal (GI) disorders were reported more frequently with liraglutide than placebo, but most events were transient, and mild or moderate in severity.Liraglutide, with diet and exercise, maintained weight loss achieved by caloric restriction and induced further weight loss over 56 weeks. Improvements in some cardiovascular disease-risk factors were also observed. Liraglutide, prescribed as 3.0 mg per day, holds promise for improving the maintenance of lost weight. more...

Objective It is unclear whether all obese individuals should be prescribed weight loss (WL) treatment. The effect of a clinically significant WL of 5% on metabolic factors among metabolically normal and abnormal overweight and obese (MNO and MAO) individuals was examined. Design and Methods The sample included 392 overweight and obese adults from the Wharton Medical Clinic. MAO was defined as having one or more clinically relevant aberrations in glucose, triglycerides, blood pressure (BP), high-density lipoprotein-C, low-density lipoprotein-C, preexisting, or current medication use for metabolic conditions. Results Of the 392 patients, 21.2% of the sample was MNO at baseline and 41.3% of the sample attained a 5% WL. Regardless of initial metabolic health status, improvements in most risk factors were observed with a 5% WL in comparison with those who did not lose weight. Even MAO patients who did not achieve a 5% WL still significantly improved BP and cholesterol over the treatment period. Conclusions A clinically significant WL is beneficial for the cardiometabolic risk profile of both MNO and MAO. However, a 5% WL is not necessarily required to improve the cardiometabolic risk profile of MAO. Thus, lifestyle-based WL provides beneficial metabolic effects for all overweight and obese individuals, particularly those with significant metabolic aberrations. more...

Summary Limited evidence is available on the effectiveness of publicly funded weight loss (WL) clinics. We examined the 1-year WL outcomes and investigated predictors of WL and discontinuation of 1566 overweight and obese adults, who attended the Wharton Medical Clinic (WMC) weight management centre for at least 6 months. Overall, 42.7% (n = 669) of the entire sample achieved a ≥5%WL over the entire follow-up period from July 2008 to February 2012. On average, patients lost 5.6 ± 7.2 kg (5.0 ± 6.3%) of initial body weight (BW), while a subsample of patients attending the clinic for at least 1 year had a mean weight reduction of 6.6 ± 7.9 kg (5.9 ± 7.2%) of BW. Older patients were more likely to achieve a greater WL in comparison with young patients while White patients and those without type 2 diabetes (T2D) lost almost twice as much weight and %BW in comparison with Asian patients and patients with T2D, respectively (P 0.05). Results of this study demonstrate that the WMC provides a practical model for clinically effective lifestyle-based treatment, accessible to a wide range of demographically diverse adults. more...

What is already known about this subject • There is a discrepancy between clinical and patient goals for weight loss. • Evidence suggests that some bariatric patients highly value, and are willing to endure hardships for weight loss. • Obesity is commonly framed as an easily reversed and individual problem, which in turn promotes weight discrimination. What this study adds • Patient beliefs about weight loss are in accordance with social understandings of obesity but not with current treatment options. • Patients may not be willing to endure hardships for weight loss. • Weight discrimination may relate to how patients approach weight loss. Summary Bariatric patients report weight loss goals, which are three times higher than weight loss recommended by clinicians. It is unclear which weight loss interventions patients feel are necessary to reach these goals or whether responses associate with perceptions of weight discrimination. One hundred fifteen patients (BMI = 40.0 ± 6.9 kg m−2, age = 47.2 ± 12.2 years, 85% female, 77% reporting weight discrimination) were surveyed from weight management clinics. Participants reported ideal weight losses of 37.6 ± 16.7 kg (33% of initial weight), and the majority felt weight loss could be achieved through lifestyle changes such as improved physical activity (80%) or diet (52%), with fewer reporting pharmacotherapy (8%), surgery (12%) or genetic modification (7%) as necessary for goal attainment. Participants selecting lifestyle changes or pharmacotherapy for weight loss reported ideal weight loss goals that would generally be achievable through surgical means (32% and 33%, respectively), and participants selecting surgical intervention reported ideal goals at the upper end of what is generally achievable with this intervention (38%). All participants selecting surgery or genetic modifications reported experiencing weight discrimination. These results indicate a disparity between weight loss goals and selected interventions, and suggest that weight discrimination is associated with the selection of potentially riskier weight loss interventions. more...

Background Our objective was to identify factors that are independently associated with early attrition and successful weight loss (WL) in an obesity-management program. Methods Participants were 9,498 patients enrolled in treatment at the Wharton Weight Management Clinic for at least 6 months. Predictors of early attrition ( more...

Since the 1980s, the prevalence of obesity has almost doubled worldwide. Treatments for obesity include lifestyle modification, medications and surgery. Newer anti-obesity medications have been shown to be effective at inducing initial weight management in addition to successful long-term weight maintenance. Historically, weight management medications have been associated with public safety concerns that have resulted in the majority being withdrawn from the market or never receiving medicinal authorization. Recently, several countries have approved some newer generation weight management medications which may be beneficial to combat obesity. These medications have varying effects on cardiometabolic parameters, both positive and potentially negative. This review will outline the mechanisms of action of these medications and their implications for both diabetes and cardiovascular risks. more...

Objectives. To determine the distribution of EOSS stages and differences in weight loss achieved according to EOSS stage, in patients attending a referral-based publically funded multisite weight management clinic.Subjects/Methods. 5,787 obese patients were categorized using EOSS staging using metabolic risk factors, medication use, and severity of doctor diagnosis of obesity-related physiological, functional, and psychological comorbidities from electronic patient files.Results. The prevalence of EOSS stages 0 (no risk factors or comorbidities), 1 (mild conditions), 2 (moderate conditions), and 3 (severe conditions) was 1.7%, 10.4%, 84.0%, and 3.9%, respectively. Prehypertension (63%), hypertension (76%), and knee replacement (33%) were the most common obesity-related comorbidities for stages 1, 2, and 3, respectively. In the models including age, sex, initial BMI, EOSS stage, and treatment time, lower EOSS stage and longer treatment times were independently associated with greater absolute (kg) and percentage of weight loss relative to initial body weightP<0.05.Conclusions. Patients attending this publicly funded, referral-based weight management clinic were more likely to be classified in the higher stages of EOSS. Patients in higher EOSS stages required longer treatment times to achieve similar weight outcomes as those in lower EOSS stages. more...

To determine whether there is an association between moderate alcohol consumption in the first trimester of pregnancy and increased risk of fetal malformations, we conducted a literature search using Medline (1966-present), PsycLit (1974-1995), and EMBASE (1988-1995). The following inclusion criteria were used to select the studies to be evaluated: 1) pregnant women; 2) moderate alcohol consumption (> 2 drinks/week to 2 drinks/day); 3) case-control or cohort studies; 4) presence of an abstainer group (0 to 2 drinks/wk); 5) outcome measures include major or minor malformations; 6) papers published in the English language. The exclusion criteria were: 1) studies in which moderate alcohol consumption could not be confirmed; 2) case reports, and editorials. The Methods section of each study was examined independently by two blinded investigators with a third investigator settling any disagreement. The number of malformations in the abstainer and moderate alcohol consuming groups in two by two tables. Out of 24 studies which met the inclusion criteria, only seven had extractable data. The included studies evaluated 130,810 pregnancy outcomes, with 24,007 in the moderate alcohol group and 106,803 in the control group. An overall Mantel-Haenszel odds ratio showed that the relative risk for fetal malformations was 1.01 with 95% confidence limits of 0.94 to 1.08 and a chi-square for homogeneity of 8.26 (p = 0.220). Quality of the studies did not correlate with their showing negative or positive association. Moderate alcohol consumption during the first trimester of pregnancy is not associated with increased risk of fetal malformations. more...

We sought to evaluate the effect of weight loss on echocardiographic epicardial fat thickness, as index of visceral adiposity, and whether epicardial fat change after the weight loss can be proportionally different from overall body weight changes and related to cardiac parameters changes in severely obese subjects. This was an interventional study in 20 severely obese subjects (12 women, 8 men, BMI 45 ± 5 kg/m2, 35 ± 10 years) who underwent 6-month very low calorie diet weight loss program. Baseline and after 6-month weight loss anthropometrics, echocardiographic epicardial fat thickness, left ventricular mass (LVM), and diastolic function parameters were assessed. Subjects lost 20% of original body weight, BMI reduced by 19% of original BMI, waist circumference decreased by 23% of initial waist circumference. Epicardial fat thickness decreased from 12.3 ± 1.8 to 8.3 ± 1 mm P < 0.001 after the 6-month very low calorie diet, as −32% of baseline epicardial fat thickness. LVM and diastolic function changes were better correlated with epicardial fat changes. We showed that significant weight loss can be associated with significant reduction in the epicardial fat thickness, marker of visceral adiposity in severely obese subjects. Epicardial fat decrease, therefore visceral fat decrease, can be proportionally higher than overall adiposity decrease. Epicardial fat changes are significantly associated with obesity-related cardiac morphological and functional changes during weight loss. Measurement of echocardiographic epicardial fat thickness may provide an additional tool in understanding the metabolic risk associated with variation in fat distribution. more...

Obesity, one of the most prevalent health problems in the Western world, is a chronic and progressive condition. Therefore, as with other chronic diseases, patients with obesity require lifelong treatment. Long-term efficacy and effectiveness of obesity treatments is notoriously poor. This may in part be attributable to the substantial barriers that undermine long-term obesity management strategies. These can include lack of recognition of obesity as a chronic condition, low socioeconomic status, time constraints, intimate saboteurs, and a wide range of comorbidities including mental health, sleep, chronic pain, musculoskeletal, cardiovascular, respiratory, digestive and endocrine disorders. Furthermore, medications used to treat some of these disorders may further undermine weight-loss efforts. Lack of specific obesity training of health professionals, attitudes and beliefs as well as coverage and availability of obesity treatments can likewise pose important barriers. Health professionals need to take care to identify, acknowledge and address these barriers where possible to increase patient success as well as compliance and adherence with treatments. Failure to do so may further undermine the sense of failure, low self esteem and self efficacy already common among obese individuals. Addressing treatment barriers can save resources and increase the prospect of long-term success. more...