weight loss

Once-Weekly Semaglutide in Adults with Overweight or Obesity

Author/s: 
Wilding, John P.H., Batterham, Rachel L., Calanna, Salvatore, Davies, Melanie, Van Gaal, Luc F., Lingvay, Ildiko, McGowan, Barbara M., Rosenstock, Julio, Tran, Marie T.D., Wadden, Thomas A.,, Sean, Yokote, Koutaro, Zeuthen, Niels, Kushner, Robert F., STEP 1 Study Group

Background: 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.

Methods: 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.

Results: 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; P<0.001). 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 (P<0.001 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%]).

Conclusions: 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).

Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial

Author/s: 
Wadden, Thomas A., Bailey, Timothy S., Billings, Liana K., Davies, Melanie, Frias, Juan P., Koroleva, Anna, Lingvay, Ildiko, O'Neil, Patrick M., Runino, Domenica M., Skovgaard, Dorthe, Wallenstein, Signe O.R., Garvey, W. TImothy, STEP 3 Investigators

Importance: Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches.

Objective: To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity.

Design, setting, and participants: Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30).

Interventions: Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks.

Main outcomes and measures: The co-primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight.

Results: Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was -16.0% for semaglutide vs -5.7% for placebo (difference, -10.3 percentage points [95% CI, -12.0 to -8.6]; P < .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P < .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants.

Conclusions and relevance: Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings.

A Randomized, Controlled Trial of Liraglutide for Adolescents With Obesity

Author/s: 
Kelly, AS, Auerbach, P, Barrientos-Perez, M, Gies, I, Hale, PM, Marcus, C, Mastrandrea, LD, Prabhu, N, Arslanian, S, NN8022-4180 Trial Investigators

Background: Obesity is a chronic disease with limited treatment options in pediatric patients. Liraglutide may be useful for weight management in adolescents with obesity.

Methods: In this randomized, double-blind trial, which consisted of a 56-week treatment period and a 26-week follow-up period, we enrolled adolescents (12 to <18 years of age) with obesity and a poor response to lifestyle therapy alone. Participants were randomly assigned (1:1) to receive either liraglutide (3.0 mg) or placebo subcutaneously once daily, in addition to lifestyle therapy. The primary end point was the change from baseline in the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) standard-deviation score at week 56.

Results: A total of 125 participants were assigned to the liraglutide group and 126 to the placebo group. Liraglutide was superior to placebo with regard to the change from baseline in the BMI standard-deviation score at week 56 (estimated difference, -0.22; 95% confidence interval [CI], -0.37 to -0.08; P = 0.002). A reduction in BMI of at least 5% was observed in 51 of 113 participants in the liraglutide group and in 20 of 105 participants in the placebo group (estimated percentage, 43.3% vs. 18.7%), and a reduction in BMI of at least 10% was observed in 33 and 9, respectively (estimated percentage, 26.1% vs. 8.1%). A greater reduction was observed with liraglutide than with placebo for BMI (estimated difference, -4.64 percentage points) and for body weight (estimated difference, -4.50 kg [for absolute change] and -5.01 percentage points [for relative change]). After discontinuation, a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (estimated difference, 0.15; 95% CI, 0.07 to 0.23). More participants in the liraglutide group than in the placebo group had gastrointestinal adverse events (81 of 125 [64.8%] vs. 46 of 126 [36.5%]) and adverse events that led to discontinuation of the trial treatment (13 [10.4%] vs. 0). Few participants in either group had serious adverse events (3 [2.4%] vs. 5 [4.0%]). One suicide, which occurred in the liraglutide group, was assessed by the investigator as unlikely to be related to the trial treatment.

Conclusions: In adolescents with obesity, the use of liraglutide (3.0 mg) plus lifestyle therapy led to a significantly greater reduction in the BMI standard-deviation score than placebo plus lifestyle therapy. (Funded by Novo Nordisk; NN8022-4180 ClinicalTrials.gov number, NCT02918279.).

Mental Health Conditions Among Patients Seeking and Undergoing Bariatric Surgery: A Meta-analysis

Author/s: 
Dawes, AJ, Maggard-Gibbons, M, Maher, AR, Booth, MJ, Miake-Lye, I, Shekelle, PG

IMPORTANCE:

Bariatric surgery is associated with sustained weight loss and improved physical health status for severely obese individuals. Mental health conditions may be common among patients seeking bariatric surgery; however, the prevalence of these conditions and whether they are associated with postoperative outcomes remains unknown.

OBJECTIVE:

To determine the prevalence of mental health conditions among bariatric surgery candidates and recipients, to evaluate the association between preoperative mental health conditions and health outcomes following bariatric surgery, and to evaluate the association between surgery and the clinical course of mental health conditions.

DATA SOURCES:

We searched PubMed, MEDLINE on OVID, and PsycINFO for studies published between January 1988 and November 2015. Study quality was assessed using an adapted tool for risk of bias; quality of evidence was rated based on GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria.

FINDINGS:

We identified 68 publications meeting inclusion criteria: 59 reporting the prevalence of preoperative mental health conditions (65,363 patients) and 27 reporting associations between preoperative mental health conditions and postoperative outcomes (50,182 patients). Among patients seeking and undergoing bariatric surgery, the most common mental health conditions, based on random-effects estimates of prevalence, were depression (19% [95% CI, 14%-25%]) and binge eating disorder (17% [95% CI, 13%-21%]). There was conflicting evidence regarding the association between preoperative mental health conditions and postoperative weight loss. Neither depression nor binge eating disorder was consistently associated with differences in weight outcomes. Bariatric surgery was, however, consistently associated with postoperative decreases in the prevalence of depression (7 studies; 8%-74% decrease) and the severity of depressive symptoms (6 studies; 40%-70% decrease).

CONCLUSIONS AND RELEVANCE:

Mental health conditions are common among bariatric surgery patients-in particular, depression and binge eating disorder. There is inconsistent evidence regarding the association between preoperative mental health conditions and postoperative weight loss. Moderate-quality evidence supports an association between bariatric surgery and lower rates of depression postoperatively.

Changes in nut consumption influence long-term weight change in US men and women

Author/s: 
X, Li, Y, Guasch-Ferre, M, Willett, WC, Drouin-Chartier, JP, Bhupathiraju, SN, Tobias, DK

Background Nut consumption has increased in the US but little evidence exists on the association between changes in nut consumption and weight change. We aimed to evaluate the association between changes in total consumption of nuts and intakes of different nuts (including peanuts) and long-term weight change, in three independent cohort studies.

Methods and findings Data collected in three prospective, longitudinal cohorts among health professionals in the US were analysed. We included 27 521 men (Health Professionals Follow-up Study, 1986 to 2010), 61 680 women (Nurses’ Health Study, 1986 to 2010), and 55 684 younger women (Nurses’ Health Study II, 1991 to 2011) who were free of chronic disease at baseline in the analyses. We investigated the association between changes in nut consumption over 4-year intervals and concurrent weight change over 20–24 years of follow-up using multivariate linear models with an unstructured correlation matrix to account for within-individual repeated measures. 21 322 individuals attained a body mass index classification of obesity (BMI ≥30 kg/m2) at the end of follow-up.

Average weight gain across the three cohorts was 0.32 kg each year. Increases in nut consumption, per 0.5 servings/day (14 g), was significantly associated with less weight gain per 4-year interval (p<0.01 for all): −0.19 kg (95% CI -0.21 to -0.17) for total consumption of nuts, -0.37 kg (95% CI -0.45 to -0.30) for walnuts, -0.36 kg (95% CI -0.40 to -0.31) for other tree nuts, and -0.15 kg (95% CI -0.19 to -0.11) for peanuts.

Increasing intakes of nuts, walnuts, and other tree nuts by 0.5 servings/day was associated with a lower risk of obesity. The multivariable adjusted RR for total nuts, walnuts, and other tree nuts was 0.97 (95% CI 0.96 to 0.99, p=0.0036), 0.85 (95% CI 0.81 to 0.89, p=0.0002), and 0.89 (95% CI 0.87 to 0.91, p<0.0001), respectively. Increasing nut consumption was also associated with a lower risk of gaining ≥2 kg or ≥5 kg (RR 0.89–0.98, p<0.01 for all).

In substitution analyses, substituting 0.5 servings/day of nuts for red meat, processed meat, French fries, desserts, or potato, chips (crisps) was associated with less weight gain (p<0.05 for all).

Our cohorts were largely composed of Caucasian health professionals with relatively higher socioeconomic status; thus the results may not be generalisable to other populations.

Conclusion Increasing daily consumption of nuts is associated with less long-term weight gain and a lower risk of obesity in adults. Replacing 0.5 servings/day of less healthful foods with nuts may be a simple strategy to help prevent gradual long-term weight gain and obesity.

Keywords 

Association of Metabolic Surgery With Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes and Obesity

Author/s: 
Aminian, A, Zajicheck, A, Arterburn, DE, Wolski, KE, Brethauer, SA, Schauer, PR, Kattan, MW, Nissen, SE

IMPORTANCE:

Although metabolic surgery (defined as procedures that influence metabolism by inducing weight loss and altering gastrointestinal physiology) significantly improves cardiometabolic risk factors, the effect on cardiovascular outcomes has been less well characterized.

OBJECTIVE:

To investigate the relationship between metabolic surgery and incident major adverse cardiovascular events (MACE) in patients with type 2 diabetes and obesity.

DESIGN, SETTING, AND PARTICIPANTS:

Of 287 438 adult patients with diabetes in the Cleveland Clinic Health System in the United States between 1998 and 2017, 2287 patients underwent metabolic surgery. In this retrospective cohort study, these patients were matched 1:5 to nonsurgical patients with diabetes and obesity (body mass index [BMI] ≥30), resulting in 11 435 control patients, with follow-up through December 2018.

EXPOSURES:

Metabolic gastrointestinal surgical procedures vs usual care for type 2 diabetes and obesity.

MAIN OUTCOMES AND MEASURES:

The primary outcome was the incidence of extended MACE (composite of 6 outcomes), defined as first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation. Secondary end points included 3-component MACE (myocardial infarction, ischemic stroke, and mortality) and the 6 individual components of the primary end point.

RESULTS:

Among the 13 722 study participants, the distribution of baseline covariates was balanced between the surgical group and the nonsurgical group, including female sex (65.5% vs 64.2%), median age (52.5 vs 54.8 years), BMI (45.1 vs 42.6), and glycated hemoglobin level (7.1% vs 7.1%). The overall median follow-up duration was 3.9 years (interquartile range, 1.9-6.1 years). At the end of the study period, 385 patients in the surgical group and 3243 patients in the nonsurgical group experienced a primary end point (cumulative incidence at 8-years, 30.8% [95% CI, 27.6%-34.0%] in the surgical group and 47.7% [95% CI, 46.1%-49.2%] in the nonsurgical group [P < .001]; absolute 8-year risk difference [ARD], 16.9% [95% CI, 13.1%-20.4%]; adjusted hazard ratio [HR], 0.61 [95% CI, 0.55-0.69]). All 7 prespecified secondary outcomes showed statistically significant differences in favor of metabolic surgery, including mortality. All-cause mortality occurred in 112 patients in the metabolic surgery group and 1111 patients in the nonsurgical group (cumulative incidence at 8 years, 10.0% [95% CI, 7.8%-12.2%] and 17.8% [95% CI, 16.6%-19.0%]; ARD, 7.8% [95% CI, 5.1%-10.2%]; adjusted HR, 0.59 [95% CI, 0.48-0.72]).

CONCLUSIONS AND RELEVANCE:

Among patients with type 2 diabetes and obesity, metabolic surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident MACE. The findings from this observational study must be confirmed in randomized clinical trials.

TRIAL REGISTRATION:

ClinicalTrials.gov Identifier: NCT03955952.

Effect of a Long Bout Versus Short Bouts of Walking on Weight Loss During a Weight‐Loss Diet: A Randomized Trial

Author/s: 
Madjd, Amenah, Taylor, Moira A., Delavari, Alireza,, Reza, Macdonald, Ian A., Farshchi, Hamid R.

OBJECTIVE:

This study aimed to evaluate the effect of different daily physical activity (PA) frequencies, while maintaining the same daily volume of PA, on weight loss, carbohydrate metabolism, and lipid metabolism in women with overweight or obesity throughout a 24-week intervention.

METHODS:

During their weight-loss plan, 65 women (BMI = 27-35 kg/m2 ; age = 18-40 years) who had a sedentary lifestyle were randomly allocated to the following groups: diet plus a long bout of moderate physical activity (LBP) (one 50-minute bout of moderate-intensity PA) 6 d/wk or diet plus short bouts of moderate physical activity (SBP) (two 25-minute bouts of moderate-intensity PA) 6 d/wk. Anthropometric and blood measurements were taken at baseline and at 24 weeks.

RESULTS:

Compared with the LBP group, the SBP group had a greater decrease in weight (SBP: -8.08 ± 2.20 kg; LBP: -6.39 ± 2.28 kg; P = 0.019), BMI (SBP: -3.11 ± 0.87 kg/m2 ; LBP: -2.47 ± 0.86 kg/m2 ; P = 0.027), and waist circumference (SBP: -8.78 ± 2.62 cm; LBP: -5.76 ± 2.03 cm; P = 0.026). No significant differences were seen in carbohydrate and lipid metabolism characteristics after 24 weeks.

CONCLUSIONS:

PA undertaken in two shorter bouts per day could be more effective for weight loss than PA undertaken in a daily long bout in adult women in a 24-week weight-loss program.

Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial

Author/s: 
Gardner, Christopher G., Trepanowski, John F., Del Gobbo, Liana C., Hauser, Michelle E., Rigdon, Joseph, Ionnidis, John P. A., Desai, Manisha, King, Abby C.

Importance

Dietary modification remains key to successful weight loss. Yet, no one dietary strategy is consistently superior to others for the general population. Previous research suggests genotype or insulin-glucose dynamics may modify the effects of diets.

Objective

To determine the effect of a healthy low-fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change and if genotype pattern or insulin secretion are related to the dietary effects on weight loss.

Design, Setting, and Participants

The Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) randomized clinical trial included 609 adults aged 18 to 50 years without diabetes with a body mass index between 28 and 40. The trial enrollment was from January 29, 2013, through April 14, 2015; the date of final follow-up was May 16, 2016. Participants were randomized to the 12-month HLF or HLC diet. The study also tested whether 3 single-nucleotide polymorphism multilocus genotype responsiveness patterns or insulin secretion (INS-30; blood concentration of insulin 30 minutes after a glucose challenge) were associated with weight loss.

Interventions

Health educators delivered the behavior modification intervention to HLF (n = 305) and HLC (n = 304) participants via 22 diet-specific small group sessions administered over 12 months. The sessions focused on ways to achieve the lowest fat or carbohydrate intake that could be maintained long-term and emphasized diet quality.

Main Outcomes and Measures

Primary outcome was 12-month weight change and determination of whether there were significant interactions among diet type and genotype pattern, diet and insulin secretion, and diet and weight loss.

Results

Among 609 participants randomized (mean age, 40 [SD, 7] years; 57% women; mean body mass index, 33 [SD, 3]; 244 [40%] had a low-fat genotype; 180 [30%] had a low-carbohydrate genotype; mean baseline INS-30, 93 μIU/mL), 481 (79%) completed the trial. In the HLF vs HLC diets, respectively, the mean 12-month macronutrient distributions were 48% vs 30% for carbohydrates, 29% vs 45% for fat, and 21% vs 23% for protein. Weight change at 12 months was −5.3 kg for the HLF diet vs −6.0 kg for the HLC diet (mean between-group difference, 0.7 kg [95% CI, −0.2 to 1.6 kg]). There was no significant diet-genotype pattern interaction (P = .20) or diet-insulin secretion (INS-30) interaction (P = .47) with 12-month weight loss. There were 18 adverse events or serious adverse events that were evenly distributed across the 2 diet groups.

Conclusions and Relevance

In this 12-month weight loss diet study, there was no significant difference in weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss. In the context of these 2 common weight loss diet approaches, neither of the 2 hypothesized predisposing factors was helpful in identifying which diet was better for whom.

Keywords 

Short- and Long-Term Outcomes after Bariatric Surgery in the Medicare Population

Author/s: 
Orestis, A. Panagiotou, Markozannes, Georgios, Kowalski, Rishi, Di, Mengyang, Bond, Dale S., Ryder, Beth A., Adam, Gaelen P., Trikalinos, Thomas A.

Introduction. We conducted a technology assessment to summarize and appraise the current evidence regarding the effectiveness and safety of bariatric surgery in the Medicare-eligible population.

Data Sources. We searched six bibliographic databases and the reference lists of published clinical practice guidelines, relevant narrative and systematic reviews, and scientific information packages from manufacturers and other stakeholders on the outcomes and prediction models of different bariatric procedures studied in the Medicare-eligible population.

Results. Of 126 eligible studies, 83 described outcomes after bariatric therapy and 43 described predictors of body weight loss or absolute body weight after bariatric therapy. We did not identify any randomized clinical trials in the Medicare-eligible population. Studies examined surgical modalities. There were no studies on endoscopically-performed bariatric procedures. Only 15 studies had a design and/or analytical approach that allowed inferences for causal treatment effects on weight loss outcomes, adverse events/complications, or other non-weightloss outcomes. Bariatric surgery in the Medicare-eligible population leads to improvements in weight loss and non-weight-loss outcomes, particularly mortality, metabolic, cardiovascular, respiratory, and musculoskeletal outcomes, and polypharmacy but the strength of evidence is low to moderate. There is moderate evidence that Roux-en-Y gastric bypass performs better compared to sleeve gastrectomy or adjustable gastric banding for metabolic, cardiovascular, and renal function outcomes and for postoperative complications. Finally, no models to predict weight loss have undergone internal or external validation.

Conclusions. Relatively few nonrandomized studies examine the comparative effectiveness and safety of bariatric therapies in the Medicare population. Large gaps remain in regard to comparisons of individual bariatric surgical procedures to each other, and very limited evidence exists in regard to patient-centered outcomes such as quality of life after surgery.

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