Dataset Information

Liraglutide 3.0 mg and Intensive Behavioral Therapy (IBT) for Obesity in Primary Care: The SCALE IBT Randomized Controlled Trial.

ABSTRACT: OBJECTIVE:Previous studies have shown additive weight loss when intensive behavioral therapy (IBT) was combined with weight-loss medication. The present multisite study provides the first evaluation, in primary care, of the effect of the Centers for Medicare and Medicaid Services-based IBT benefit, delivered alone (with placebo) or in combination with liraglutide 3.0 mg. METHODS:The Satiety and Clinical Adiposity-Liraglutide Evidence in individuals with and without diabetes (SCALE) IBT was a 56-week, randomized, double-blind, placebo-controlled, multicenter trial in individuals with obesity who received liraglutide 3.0 mg (n?=?142) or placebo (n?=?140) as an adjunct to IBT. RESULTS:At week 56, mean weight loss with liraglutide 3.0 mg plus IBT was 7.5% and 4.0% with placebo combined with IBT (estimated treatment difference [95% CI]-3.4% [-5.3% to -1.6%], P?=?0.0003). Significantly more individuals on liraglutide 3.0 mg than placebo achieved ??5% weight loss (61.5% vs. 38.8%; odds ratio [OR] 2.5% [1.5% to 4.1%], P?=?0.0003), >?10% weight loss (30.5% vs. 19.8%; OR 1.8% [1.0% to 3.1%], P?=?0.0469), and >?15% weight loss (18.1% vs. 8.9%; OR 2.3% [1.1% to 4.7%], P?=?0.0311). Liraglutide 3.0 mg in combination with IBT was well tolerated, with no new safety signals identified. CONCLUSIONS:In a primary care setting, Centers for Medicare and Medicaid Services-based IBT produced clinically meaningful weight loss at 56 weeks, enhanced by the addition of liraglutide 3.0 mg.

SUBMITTER: Wadden TA

PROVIDER: S-EPMC7065111 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Liraglutide 3.0 mg and Intensive Behavioral Therapy (IBT) for Obesity in Primary Care: The SCALE IBT Randomized Controlled Trial.

Wadden Thomas A TA Tronieri Jena Shaw JS Sugimoto Danny D Lund Michael Taulo MT Auerbach Pernille P Jensen Camilla C Rubino Domenica D

Obesity (Silver Spring, Md.) 20200301 3

<h4>Objective</h4>Previous studies have shown additive weight loss when intensive behavioral therapy (IBT) was combined with weight-loss medication. The present multisite study provides the first evaluation, in primary care, of the effect of the Centers for Medicare and Medicaid Services-based IBT benefit, delivered alone (with placebo) or in combination with liraglutide 3.0 mg.<h4>Methods</h4>The Satiety and Clinical Adiposity-Liraglutide Evidence in individuals with and without diabetes (SCALE ...[more]

PMID: 32090517

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Project description:Abstract In this 56-week, randomized, double-blind, US-based multicenter trial (NCT02963935) we investigated the effects of liraglutide 3.0 mg vs placebo, as adjunct to intensive behavior therapy (IBT) (i.e. reduced calorie intake, increased physical activity [max target: 250 min/week], and 23 counseling sessions). Here we report the effects of treatment on weight change (co-primary endpoints: mean change in body weight [%] and proportion of individuals losing ≥5%), glycemic variables, cardiometabolic risk factors, safety and tolerability. Individuals aged ≥18 years with a body mass index (BMI) ≥30 kg/m2 and without diabetes were randomized 1:1 to liraglutide 3.0 mg or placebo along with IBT. Continuous and categorical variables were calculated using analysis of covariance (ANCOVA) and logistic regression respectively, with treatment, gender and BMI as factors and baseline endpoint as a covariate. Missing values were handled using a jump-to-reference multiple imputation model. There were 282 individuals in the full analysis set; 142 were randomized to liraglutide 3.0 mg (45 y, 16% male, 109 kg, 39 kg/m2) and 140 to placebo (49 y, 17% male, 107 kg, 39 kg/m2); 99% and 93% completed the trial, respectively. The intention to treat analysis demonstrated weight loss at 56 weeks of 7.5% with liraglutide 3.0 mg and 4.0% with placebo (estimated treatment difference (ETD) [95% CI], 3.5% [5.3, 1.6]; p=0.0003). Weight loss in individuals on trial product at 56 weeks was 9.1% (n=114) and 4.8% (n=103), respectively. The proportion of individuals achieving ≥5% weight loss was 61.5% with liraglutide 3.0 mg and 38.8% with placebo (estimated odds ratio (OR) 2.5 [1.5, 4.1], p=0.0003). The proportion who lost >10% was 30.5% and 19.8% (OR 1.8 [1.01, 3.1], p=0.0469), and >15% was 18.1% and 8.9% (OR 2.3 [1.1, 4.7], p=0.0311, respectively. Change in waist circumference was -9.4 cm with liraglutide 3.0 mg vs -6.7 cm with placebo (ETD -2.7 cm [-4.7, -0.8], p=0.006). Significant improvements at 56 weeks were seen for liraglutide 3.0 mg vs placebo in both HbA1c (ETD -0.10% [-0.16, -0.04], p=0.0008) and fasting plasma glucose (ETD ‑0.23 mmol/L [-0.36, -0.11] p=0.0002). Blood pressure (BP) reductions were observed in both treatment arms at 56 weeks, but there were no significant differences between groups in systolic (ETD -2.2 mmHg [‑4.9, 0.5], p=0.11) or diastolic BP (ETD -0.2 mmHg [‑2.2, 1.8], p=0.87), or heart rate (ETD 1.3 bpm [-0.8, 3.4], p=0.23). Lipids were improved vs baseline but no significant differences between treatment arms were observed at 56 weeks (all p>0.05). Liraglutide 3.0 mg was generally well tolerated and no new safety signals were observed in this study. The most frequent adverse events were gastrointestinal (liraglutide 3.0 mg: 71%; placebo: 49%). In conclusion, liraglutide 3.0 mg as an adjunct to IBT resulted in significantly greater weight loss, as compared to IBT and placebo. Supported by Novo Nordisk.

Project description:Abstract The objective of the SCALE IBT trial (NCT02963935) was to compare the weight loss of liraglutide 3.0 mg, a medication approved by the Food and Drug Administration for chronic weight management, to placebo, both in combination with 56 weeks of intensive behavior therapy (IBT) (i.e. reduced calorie intake, increased physical activity [max target: 250 mins/week], and 23 counseling sessions). The primary outcomes of the study were assessed in the intention-to-treat sample, regardless of individuals’ medication adherence. The weight loss estimated in the primary analysis, regardless of drug adherence, was 7.5% versus 4.0% for liraglutide 3.0 mg and placebo, respectively, reflecting a treatment difference favoring liraglutide 3.0 mg of 3.5% (95% CI: 1.6%; 5.3%; p=0.0003). In this pre-specified secondary analysis, we sought to determine the expected effect of liraglutide 3.0 mg on weight loss, as compared to placebo, if all randomized individuals had adhered to study drug for 56 weeks. A total of 282 individuals with obesity (BMI ≥30 kg/m2) were randomized in a 1:1 ratio to 56 weeks of IBT combined with daily injections of either liraglutide 3.0 mg or placebo. The weight loss, based on the assumption that all individuals adhered to the medication, was estimated using two different approaches. The first approach (mixed model repeated measures; MMRM) estimated the weight loss that would have been achieved if all individuals adhered to the trial drug by utilizing information from individuals still on drug after the point of a given individual’s discontinuation to provide a (counter-factual) weight change as if the individual in question had not discontinued the drug. The second (covariate) approach used a regression model to calculate the weight change of individuals with full adherence to trial drug by including adherence as a moderator of the effect of treatment condition on weight change. The MMRM approach yielded a weight loss difference of 4.6% (95% CI: 2.6%; 6.5%; p<0.0001), and the covariate approach yielded a weight loss difference of 4.6% (95% CI: 2.8%; 6.5%; p<0.0001), with both estimates favoring liraglutide 3.0 mg. As such, there was good agreement between the two statistical approaches for estimating the effect of liraglutide 3.0 mg versus placebo for individuals who adhere to trial product for 56 weeks. The estimated placebo-subtracted weight loss for liraglutide at week 56 of approximately 4.6% in medication-adherent individuals therefore indicates that underlying assumptions are robust. We believe this finding is an important supplement to the study’s primary outcome and can inform practitioners’ expectations when prescribing liraglutide 3.0 mg in combination with IBT for 56 weeks. Supported by Novo Nordisk.

Project description:Abstract In clinical trials for weight management, changes in physical function are typically assessed with self-report HRQoL questionnaires. In this trial we aimed to objectively measure the effect of weight loss on walking capacity, as measured with the 6-minute walk test, a sub-maximal exercise test used to assess cardiopulmonary and musculoskeletal systems. The SCALE IBT trial (NCT02963935) was a 56-week, randomized, double-blind, US-based multicenter trial of liraglutide 3.0 mg vs placebo, with intensive behavior therapy (IBT) (i.e. reduced calorie intake, increased physical activity [max target: 250 min/week], and 23 counseling visits) in both arms. A key secondary endpoint was the change in 6-minute walking distance (6MWD), a test for walking capacity measured by total distance walked along a 20-m marked walkway over 6 minutes. To our knowledge, this is the first trial with pharmacological weight management to explore changes in the 6MWD in response to treatment. This post-hoc analysis examined the association between baseline body mass index (BMI) and 6MWD, and change in weight and 6MWD. For the trial, individuals aged ≥18 y with a BMI ≥30 kg/m2 and without diabetes were randomized 1:1 to IBT plus liraglutide 3.0 mg or placebo. The change in body weight and 6MWD from baseline to week 56 was calculated using analysis of covariance (ANCOVA), with treatment, gender and BMI as factors and baseline endpoint [body weight or 6MWD] as a covariate. Linear regression was used for the correlation analysis of the association between 6MWD and BMI. There were 282 individuals in the full analysis set (47 y, 17% male, BMI 39 kg/m2), of whom 142 were randomized to liraglutide 3.0 mg and 140 to placebo. At 56 weeks, mean weight loss was 7.5% with liraglutide 3.0 mg and 4.0% with placebo, estimated treatment difference (ETD [95% CI] 3.5% [1.6, 5.3]; p=0.0003). Improvement in 6MWD was 49.5 m vs. 46.4 m, respectively, from a mean baseline of 439 m (ETD [95% CI] 3.1 [-12.7, 18.9]; p=0.70). The post-hoc correlation analysis showed a linear relationship between 6MWD and BMI. Linear regression of baseline 6MWD vs. baseline BMI showed that on average an individual with a BMI that was 1 kg/m2 lower compared to another individual was able to walk 4.9 m longer in 6 minutes (slope [95% CI] -4.9 m/(kg/m2) [-6.2, -3.6]; p<0.0001). This relationship was also demonstrated in a linear regression analysis of change in 6MWD at 56 weeks vs. change in BMI at 56 weeks, where on average an individual improved 6MWD by 5.0 m for each BMI decrease of 1 kg/m2 (slope [95% CI] -5.0 m/(kg/m2) [-7.6, -2.5]; p<0.0001). The intercept (i.e. change in 6MWD with no change in BMI) was 36.3 m, most likely primarily reflecting the effect of increased physical activity as a part of the IBT intervention. This post-hoc analysis showed that greater weight loss was associated with greater improvements in 6MWD in a linear manner, indicating gains in walking capacity. Supported by Novo Nordisk.

Project description:Abstract Liraglutide 3.0 mg is approved by the Food and Drug Administration for chronic weight management in the United States as an adjunct to reduced caloric diet and increased physical activity. The objective of the SCALE IBT trial (NCT02963935) was to compare the weight loss for liraglutide 3.0 mg to placebo, both in combination with intensive behavioral therapy (IBT) (i.e. reduced calorie intake, increased physical activity [max target: 250 min/week], and 23 counseling sessions). The present pre-specified exploratory sub-analysis determined the individual contributions of adherence to study medication, and to the adjunct diet and physical activity interventions on weight change. A total of 282 individuals with obesity (BMI ≥30 kg/m2) were randomized to treatment for 56 weeks. Adherence to study medication was recorded on a weekly basis by individuals’ self-reports of taking at least one dose in the preceding week. Adherence to dietary recommendations was assessed via the individuals’ completion of food diaries (at least one entry per day on 5 days or more in the preceding week was considered adherent). Adherence to physical activity recommendations was assessed using electronic activity trackers by comparing measured active minutes to the program goal (starting at 100 min/week increasing to 250 min/week; achieving 50% of target in the preceding week was considered to be adherent). The proportion of randomized individuals who were adherent decreased steadily through the study for all three intervention components. The effect of adherence on body weight was evaluated through an ANOVA model that included dietary information, physical activity and medication adherence and their interaction with randomized treatment. The model was reduced by removing non-significant terms, leaving only the main effect of adherence to diet and physical activity, and the effects of adherence to study medication. As estimated in the final model, adherence to dietary recommendations throughout the trial provided a ‑7.2% reduction in initial body weight (95% CI: -10.4%; -4.0%; p<0.0001); adherence to physical activity recommendations provided -2.0% (95% CI: ‑3.2%; -0.8%; p=0.0009); and adherence to liraglutide 3.0 mg provided an additional loss of -6.5% (95% CI: ‑10.2%; ‑2.9%; p=0.0005). As expected, adherence to placebo did not have a statistically significant effect on weight loss (mean contribution of -1.9%, 95% CI: -5.6%; 1.9%; p=0.33). In conclusion, this sub-analysis indicated that adherence to dietary recommendations and liraglutide injections provided clinically relevant weight loss, whereas the effect of physical activity was more modest in size. Supported by Novo Nordisk.

Project description:BackgroundObesity is strongly associated with prevalence of obstructive sleep apnea (OSA), and weight loss has been shown to reduce disease severity.ObjectiveTo investigate whether liraglutide 3.0 mg reduces OSA severity compared with placebo using the primary end point of change in apnea-hypopnea index (AHI) after 32 weeks. Liraglutide's weight loss efficacy was also examined.Subjects/methodsIn this randomized, double-blind trial, non-diabetic participants with obesity who had moderate (AHI 15-29.9 events h(-1)) or severe (AHI ⩾30 events h(-1)) OSA and were unwilling/unable to use continuous positive airway pressure therapy were randomized for 32 weeks to liraglutide 3.0 mg (n=180) or placebo (n=179), both as adjunct to diet (500 kcal day(-1) deficit) and exercise. Baseline characteristics were similar between groups (mean age 48.5 years, males 71.9%, AHI 49.2 events h(-1), severe OSA 67.1%, body weight 117.6 kg, body mass index 39.1 kg m(-2), prediabetes 63.2%, HbA1c 5.7%).ResultsAfter 32 weeks, the mean reduction in AHI was greater with liraglutide than with placebo (-12.2 vs -6.1 events h(-1), estimated treatment difference: -6.1 events h(-1) (95% confidence interval (CI), -11.0 to -1.2), P=0.0150). Liraglutide produced greater mean percentage weight loss compared with placebo (-5.7% vs -1.6%, estimated treatment difference: -4.2% (95% CI, -5.2 to -3.1%), P<0.0001). A statistically significant association between the degree of weight loss and improvement in OSA end points (P<0.01, all) was demonstrated post hoc. Greater reductions in glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) were seen with liraglutide versus placebo (both P<0.001). The safety profile of liraglutide 3.0 mg was similar to that seen with doses ⩽1.8 mg.ConclusionsAs an adjunct to diet and exercise, liraglutide 3.0 mg was generally well tolerated and produced significantly greater reductions than placebo in AHI, body weight, SBP and HbA1c in participants with obesity and moderate/severe OSA. The results confirm that weight loss improves OSA-related parameters.

Dataset Information

Liraglutide 3.0 mg and Intensive Behavioral Therapy (IBT) for Obesity in Primary Care: The SCALE IBT Randomized Controlled Trial.

Publications

Liraglutide 3.0 mg and Intensive Behavioral Therapy (IBT) for Obesity in Primary Care: The SCALE IBT Randomized Controlled Trial.

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