scholarly journals Efficacy and Safety of Once-Weekly Subcutaneous Semaglutide 2.4 MG in Adults With Overweight or Obesity (STEP 1)

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A10-A10
Author(s):  
John P H Wilding ◽  
Rachel L Batterham ◽  
Salvatore Calanna ◽  
Melanie Davies ◽  
Luc F Van Gaal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Weight Loss ◽  
Body Weight ◽  
Weight Management ◽  
Treatment Adherence ◽  
Weight Change ◽  
Cardiometabolic Risk ◽  
Body Weight Change ◽  
Efficacy And Safety ◽  
Overweight Or Obesity

Abstract 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<0.0001). Similar results were obtained with the trial product estimand: mean body weight change# was -16.9% for semaglutide vs -2.4% for placebo (ETD: -14.4%; 95% CI: -15.3, -13.6; p<0.0001). Participants were more likely to achieve weight loss ≥5%, ≥10%, ≥15%, and ≥20%# with semaglutide vs placebo (86.4% vs 31.5%, 69.1% vs 12.0%, 50.5% vs 4.9%, and 32.0% vs 1.7%, respectively; p<0.0001 for all). Greater improvements were seen with semaglutide vs placebo in waist circumference, BMI#, systolic and diastolic# blood pressure, glycated hemoglobin#, fasting plasma glucose#, C-reactive protein#, fasting lipid profile#, and self-reported physical functioning (p<0.05 for all). No new safety signals with semaglutide were observed. The most frequent adverse events with semaglutide were gastrointestinal disorders (typically transient and mild-to-moderate). 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.

scholarly journals Efficacy and Safety of Semaglutide 2.4 MG Once-Weekly in Adults With Overweight or Obesity and Type 2 Diabetes (STEP 2)

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A10-A11
Author(s):  
Melanie Davies ◽  
Louise Færch ◽  
Ole K Jeppesen ◽  
Arash Pakseresht ◽  
Sue D Pedersen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Body Weight ◽  
Weight Management ◽  
Weight Change ◽  
Body Weight Change ◽  
Efficacy And Safety ◽  
Treatment Policy ◽  
Overweight Or Obesity

Abstract Background: In people with overweight/obesity and type 2 diabetes (T2D), achievement of weight loss can be a challenge. STEP 2 investigated the efficacy and safety of semaglutide 2.4 mg for weight management in adults with overweight/obesity and T2D. Methods: This randomized, double-blind, double-dummy, placebo-controlled, phase 3 trial was conducted at 149 sites across 12 countries (NCT03552757). Adults aged ≥18 years with body mass index (BMI) ≥27 kg/m2, T2D, HbA1c between 7–10% (53–86 mmol/mol), and receiving ≤3 oral glucose-lowering agents were randomized 1:1:1 to once-weekly subcutaneous (s.c.) semaglutide 2.4 mg or 1.0 mg, or placebo, as adjunct to a reduced-calorie diet and increased physical activity for 68 weeks. The co-primary endpoints were percentage change in body weight and proportion of participants achieving weight loss ≥5% for semaglutide 2.4 mg vs placebo. Cardiovascular risk factors, glycemia and safety/tolerability were also assessed. Two estimands were defined: treatment policy and trial product; results are presented for the treatment policy estimand, unless stated otherwise. Results: 1,210 participants (mean: age 55 years, body weight 99.8 kg, BMI 35.7 kg/m2, HbA1c 8.1%, diabetes duration 8.0 years; 50.9% female) were randomized. Mean body weight change from baseline to week 68 was −9.6% with semaglutide 2.4 mg vs −3.4% with placebo (estimated treatment difference [ETD]: −6.2%; 95% confidence interval [CI]: −7.3, −5.2; p<0.0001) and −7.0% for semaglutide 1.0 mg (ETD for semaglutide 2.4 mg vs 1.0 mg: −2.7%; 95% CI: −3.7, −1.6; p<0.0001). Similar results were obtained with the trial product estimand: mean body weight change −10.6% for semaglutide 2.4 mg vs −3.1% for placebo (ETD: −7.6%; 95% CI: −8.6, −6.6; p<0.0001) and 7.6% for semaglutide 1.0 mg (ETD vs semaglutide 2.4 mg: −3.1%; 95% CI: −4.1, −2.1; p<0.0001). Participants on semaglutide 2.4 mg were more likely to achieve weight loss ≥5%, ≥10%, ≥15% and ≥20% vs placebo (68.8% vs 28.5%, 45.6% vs 8.2%, 25.8% vs 3.2% and 13.1% vs 1.6%, respectively; p value for odds ratios <0.0001 for all). Mean change in HbA1c from baseline to week 68 was −1.6% for semaglutide 2.4 mg vs −0.4% for placebo (p<0.0001). Greater improvements with semaglutide 2.4 mg vs placebo were also seen in waist circumference, BMI, systolic blood pressure, fasting plasma glucose, C-reactive protein, and lipids (HDL, VLDL, free fatty acids, and triglycerides) (p<0.05 for all). The most frequent adverse events were gastrointestinal disorders (typically transient and mild-to-moderate), occurring in 57.5%, 63.5% and 34.3% of participants receiving semaglutide 1.0 mg, 2.4 mg and placebo, respectively. Conclusion: Semaglutide 2.4 mg, as adjunct to lifestyle intervention, was efficacious and well tolerated for weight management in adults with overweight or obesity and T2D, providing significantly greater weight loss vs placebo and semaglutide 1.0 mg at week 68.

scholarly journals Longitudinal Body Weight Change, Visit-To-Visit Body Weight Fluctuation, and Cognitive Decline Among Older Adults

2021 ◽  
pp. 1-9
Author(s):  
Yu-Tung Lan ◽  
Deborah Blacker ◽  
Changzheng Yuan ◽  
Lori B. Chibnik ◽  
Albert Hofman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Weight Loss ◽  
Body Weight ◽  
Cognitive Decline ◽  
Weight Change ◽  
Cardiometabolic Risk ◽  
Late Life ◽  
Body Weight Change ◽  
Weight Fluctuation ◽  
Traditional Risk Factors

Background: The evidence regarding dementia and late-life weight change is inconsistent, and data on body weight fluctuation and dementia are limited. Objective: To test the hypothesis that weight loss and substantial weight fluctuation predict cognitive decline independent of body weight and traditional risk factors of dementia. Methods: This study utilized longitudinal data from the National Alzheimer’s Coordinating Center for 10,639 stroke- and dementia-free older adults (60.9%female, mean age 71.6 years, median follow-up 5.5 years). Trends in weight change and weight fluctuation were estimated for each individual by regressing repeated body weight measurements on time. Cognitive decline was examined as diagnostic progression from normal to mild cognitive impairment (MCI) or dementia and from MCI to dementia. Results: Compared to participants with stable weight, those with weight loss had increased odds of diagnostic progression (adjusted OR = 1.35, 95%CI [1.21, 1.51]). Also, large weight fluctuation was associated with increased odds of diagnostic progression (OR comparing the extreme quartiles = 1.20, 95%CI [1.04, 1.39]) after adjusting for traditional risk factors for dementia and body weight change. The magnitude of the association appeared larger among those older than 80 and those with 3 or more cardiometabolic risk factors at baseline (both p for interaction <  0.05). Conclusion: Weight loss and substantial weight fluctuation during late-life were associated with increased odds of cognitive decline independent of body weight and traditional risk factors of dementia. Our results suggested the linkage between late-life body weight instability and cognitive decline especially among those with greater age or higher cardiometabolic risk.

scholarly journals Dietary sugars and cardiometabolic risk: Systematic review and meta-analyses of randomized controlled trials of the effects on blood pressure and lipids

2020 ◽  
Author(s):  
Lisa Te Morenga ◽  
AJ Howatson ◽  
RM Jones ◽  
J Mann
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Blood Pressure ◽  
Body Weight ◽  
Weight Change ◽  
Cardiometabolic Risk ◽  
Controlled Trials ◽  
Free Sugars ◽  
Randomized Controlled ◽  
Dietary Sugars

Background: Dietary sugars have been suggested as a cause of obesity, several chronic diseases, and a range of cardiometabolic risk factors, but there is no convincing evidence of a causal relation between sugars and risk factors other than body weight. Objective: We conducted a systematic review and meta-analysis of randomized controlled trials that examined effects of the modification of dietary free sugars on blood pressure and lipids. Design: Systematic searches were conducted in OVID Medline, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature, and Web of Science databases (to August 2013) to identify studies that reported intakes of free sugars and at least one lipid or blood pressure outcome. The minimum trial duration was 2 wk. We pooled data by using inverse-variance methods with random-effects models. Results: A total of 39 of 11,517 trials identified were included; 37 trials reported lipid outcomes, and 12 trials reported blood pressure outcomes. Higher compared with lower sugar intakes significantly raised triglyceride concentrations [mean difference (MD):0.11 mmol/L; 95% CI: 0.07, 0.15 mmol/L; P < 0.0001], total cholesterol (MD: 0.16 mmol/L; 95% CI: 0.10, 0.24 mmol/L; P < 0.0001), lowdensity lipoprotein cholesterol (0.12 mmol/L; 95% CI: 0.05, 0.19 mmol/L; P = 0.0001), and high-density lipoprotein cholesterol (MD: 0.02 mmol/L; 95% CI: 0.00, 0.03 mmol/L; P = 0.03). Subgroup analyses showed the most marked relation between sugar intakes and lipids in studies in which efforts were made to ensure an energy balance and when no difference in weight change was reported. Potential explanatory factors, including a weight change, in most instances explained <15% of the heterogeneity between studies (I2 = 36-75%). The effect of sugar intake on blood pressure was greatest in trials ≥8 wk in duration [MD: 6.9 mm Hg (95% CI: 3.4, 10.3 mm Hg; P<0.001) for systolic blood pressure and 5.6 mm Hg (95% CI: 2.5, 8.8 mm Hg; P = 0.0005) for diastolic blood pressure]. Conclusions: Dietary sugars influence blood pressure and serum lipids. The relation is independent of effects of sugars on body weight. Protocols for this review were registered separately for effects of sugars on blood pressure and lipids in the PROSPERO International prospective register of systematic reviews as PROSPERO 2012: CRD42012002379 and 2012: CRD42012002437, respectively. © 2014 American Society for Nutrition.

THE EFFECT OF SLIGHT BODY WEIGHT CHANGE ON THE CARDIOVASCULAR RISK FACTORS

1999 ◽  
Vol 31 (Supplement) ◽  
pp. S56
Author(s):  
H. Ishida ◽  
Y. Oguma ◽  
T. Takeda ◽  
F. Katsukawa ◽  
N. Kinoshita ◽  
...  
Keyword(s):  
Risk Factors ◽  
Body Weight ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Weight Change ◽  
Body Weight Change

scholarly journals Adherence to a Plant-Based Diet and Consumption of Specific Plant Foods—Associations with 3-Year Weight-Loss Maintenance and Cardiometabolic Risk Factors: A Secondary Analysis of the PREVIEW Intervention Study

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3916
Author(s):  
Ruixin Zhu ◽  
Mikael Fogelholm ◽  
Sally D. Poppitt ◽  
Marta P. Silvestre ◽  
Grith Møller ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Weight Loss ◽  
Weight Management ◽  
Cardiometabolic Risk ◽  
Ldl Cholesterol ◽  
Secondary Analysis ◽  
Weight Loss Maintenance ◽  
Cardiometabolic Risk Factors ◽  
Plant Foods

Plant-based diets are recommended by dietary guidelines. This secondary analysis aimed to assess longitudinal associations of an overall plant-based diet and specific plant foods with weight-loss maintenance and cardiometabolic risk factors. Longitudinal data on 710 participants (aged 26–70 years) with overweight or obesity and pre-diabetes from the 3-year weight-loss maintenance phase of the PREVIEW intervention were analyzed. Adherence to an overall plant-based diet was evaluated using a novel plant-based diet index, where all plant-based foods received positive scores and all animal-based foods received negative scores. After adjustment for potential confounders, linear mixed models with repeated measures showed that the plant-based diet index was inversely associated with weight regain, but not with cardiometabolic risk factors. Nut intake was inversely associated with regain of weight and fat mass and increments in total cholesterol and LDL cholesterol. Fruit intake was inversely associated with increments in diastolic blood pressure, total cholesterol, and LDL cholesterol. Vegetable intake was inversely associated with an increment in diastolic blood pressure and triglycerides and was positively associated with an increase in HDL cholesterol. All reported associations with cardiometabolic risk factors were independent of weight change. Long-term consumption of nuts, fruits, and vegetables may be beneficial for weight management and cardiometabolic health, whereas an overall plant-based diet may improve weight management only.

scholarly journals Changes and variations of body weight as risk factors for coronary heart disease

2008 ◽  
Vol 61 (5-6) ◽  
pp. 274-280 ◽  
Author(s):  
Dragana Jovanovic ◽  
Branko Jakovljevic ◽  
Katarina Paunovic ◽  
Dusan Grubor ◽  
Aleksandar Milovanovic
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Coronary Heart Disease ◽  
Weight Loss ◽  
Body Weight ◽  
Heart Disease ◽  
Weight Gain ◽  
Weight Change ◽  
Healthy Controls ◽  
Weight Changes

Introduction Weight variations are a common phenomenon. Therefore, concern has been raised about the association between weight changes and weight variations and coronary heart disease (CHD). The aim of this study was to estimate the influence of weight change and weight variations as risk factors for coronary heart disease. Materials and methods The investigation was conducted as an observational cross-sectional study, including 102 participants of both genders: 61 patients with CHD and 41 healthy controls. All participants underwent anthropometric measurements and completed a questionnaire that included 1) weight changes in adulthood (maximum and minimum weight), 2) presence and number of weight variations in the 10 years prior to the onset of disease and 3) the size of weight change (weight gain or weight loss in kg). One weight variation was defined as weight loss followed by weight gain for more than 10% of body weight, or about 7 kg. Multivariant logistic regression was used for the estimation of significant predictors for the occurrence of coronary heart disease. Results Participants with CHD had higher values of body weight in adulthood compared to healthy controls, larger number of weight variations in the last 10 years, and more frequently reported weight gain and weight loss for more than 10 kg. The highest risk for the occurrence of coronary heart disease was observed for participants who had more than 3 weight variations for 10% (OR=2.13; 95%CI=0.98-5.48), those with weight loss over 10 kg (OR=2.16; 95%CI=1.71-2.72) and those with weight gain over 10 kg (OR=2.71; 95%CI=1.08-6.83), regardless of gender, age, smoking, body mass index and blood pressure. Discussion Several mechanisms are suggested to explain the relationship between weight changes and variations and coronary heart disease, including changes in plasma lipid levels, insulin levels, decrease of HDL cholesterol, increase of C-reactive protein and increase of blood pressure. Conclusion This study suggests that frequent and very intense weight changes can be considered important predictors for the occurrence of coronary heart disease.

scholarly journals Analysis of factors contributing to postoperative body weight change in patients with gastric cancer: based on generalized estimation equation

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9390
Author(s):  
Qiuju Tian ◽  
Liyuan Qin ◽  
Weiyi Zhu ◽  
Shaojie Xiong ◽  
Beiwen Wu
Keyword(s):  
Gastric Cancer ◽  
Weight Loss ◽  
Body Weight ◽  
Cancer Patients ◽  
Total Gastrectomy ◽  
Weight Change ◽  
Body Weight Loss ◽  
Body Weight Change ◽  
Generalized Estimation Equation ◽  
Gastric Cancer Patients

Aims The study aimed to explore factors contributing to body weight change over time in gastric cancer patients after gastrectomy, in order to find risk factors to implement nutritional intervention beforehand. Methods A cohort of gastric cancer patients who were treated with gastrectomy from January to March 2019 at a university affiliated hospital in Shanghai were consecutively identified in this study. Demographics, disease related information, nutrition knowledge, attitude, and practice score were collected before gastrectomy. In addition, body weight before surgery (T0), body weight at one month (T1), two months (T2), and three months (T3) after gastrectomy were recorded. Generalized estimation equation was used to describe body weight change and analyze factors contributing to body weight change after surgery. Results There were 49 patients recruited in the study. Patient body weight decreased by 9.2% at T1 (Wald χ = 271.173, P <0.001), 11.0% at T2 (Wald χ2 = 277.267, P <0.001), and 11.4% at T3 compared to baseline at T0 (Wald χ = 284.076, P <0.001). The results of GEE for multivariable analysis showed that surgery type (Wald χ = 6.027, P = 0.014) and preoperative BMI (Wald χ = 12.662, P = 0.005) were contributing factors of body weight change. Compared with distal gastrectomy patients, total gastrectomy patients experienced greater body weight loss (β = 2.8%, P = 0.014). Compared with patients with BMI&λτ; 18.5 kg/m2, patients with BMI ≥ 25 kg/m2experienced greater body weight loss (β = 4.5% P = 0.026). Conclusion Gastric cancer patients experienced significant weight loss during 3 months after gastrectomy. Total gastrectomy and BMI ≥ 25 kg/m2were risk factors to postoperative body weight loss for GC patients. The results suggested hinted that clinician should pay attention to postoperative nutrition status of patient undergoing total gastrectomy and obesity patients.

scholarly journals Clinically-Relevant Weight Loss is Achieved Independently of Early Weight Loss Response to Once-Weekly Subcutaneous Semaglutide 2.4 MG (STEP 4)

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A7-A7
Author(s):  
Ofri Mosenzon ◽  
W Timothy Garvey ◽  
Dan Hesse ◽  
Anna Koroleva ◽  
Robert F Kushner ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Weight Change ◽  
Predictive Value ◽  
Maintenance Dose ◽  
Mixed Model ◽  
Repeated Measurements ◽  
Body Weight Change ◽  
Double Blind ◽  
Early Weight Loss

Abstract Background: Semaglutide, a glucagon-like peptide-1 analogue, is being investigated in people with overweight or obesity. A post-hoc analysis of the STEP 4 trial was conducted to identify whether early weight loss is predictive of later weight loss with maintenance once-weekly subcutaneous (s.c.) semaglutide 2.4 mg. Methods: STEP 4 was a randomized, double-blind, phase 3 withdrawal trial (NCT03548987). Adults aged ≥18 years with either body mass index (BMI) ≥27 kg/m2 with ≥1 weight-related comorbidity or BMI ≥30 kg/m2, without type 2 diabetes, underwent a 20-week run-in period. Participants reaching the maintenance dose of once-weekly s.c. semaglutide 2.4 mg at week 20 (regardless of weight loss achieved) were randomized 2:1 to semaglutide 2.4 mg or placebo, as adjunct to lifestyle intervention, for an additional 48 weeks. Percent change in body weight from week 0 to 68 was estimated using a mixed model for repeated measurements analysis with treatment, week 20 responder status, and the interaction between treatment and week 20 responder status as factors, and baseline body weight as a covariate, all nested within visit (based on the trial product estimand [treatment effect assuming treatment adherence and without use of rescue intervention] for the on-treatment period). Participants were considered responders if they achieved ≥5% weight loss at week 20. Whether the week 20 response to semaglutide predicted the achievement of clinically-relevant weight loss (≥5%) by week 68 was also assessed. Results: In STEP 4, 902 participants initiated semaglutide at week 0, of whom 803 were randomized at week 20 (semaglutide: n=535, placebo: n=268; characteristics at week 0 for all randomized participants: mean age 46 years, body weight 107.2 kg, BMI 38.4 kg/m2; 79.0% female; 83.7% white). For the 88.0% of participants randomized to semaglutide and who were responders at week 20, mean body weight change from week 0 to 68 was -19.7%. For non-responders at week 20, mean body weight change was -6.4% with continued semaglutide vs -0.3% with switch to placebo. Of all participants randomized to semaglutide, 86.2% achieved a clinically-relevant weight loss (≥5%) at week 68. Being a responder at week 20 was highly predictive of achieving this outcome (positive predictive value: 96.4%), whereas being a non-responder at week 20 had limited predictive value (negative predictive value: 42.9%). Conclusion: In the STEP 4 trial, the vast majority of participants who were randomized to the maintenance dose of once-weekly s.c. semaglutide 2.4 mg at week 20 had lost ≥5% body weight by week 68, with most achieving this by week 20. Overall weight loss with semaglutide was greater among early responders, but non-responders also achieved a clinically-relevant weight loss by week 68 if semaglutide treatment was continued.

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