scholarly journals Once-weekly Subcutaneous Semaglutide 2.4 mg Reduces Body Weight in Adults with Overweight or Obesity Regardless of Baseline Characteristics (STEP 1)

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A24-A24
Author(s):  
Robert F Kushner ◽  
W Timothy Garvey ◽  
Dan Hesse ◽  
Anna Koroleva ◽  
Soo Lim ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Mixed Model ◽  
Repeated Measurements ◽  
Phase 3 ◽  
Double Blind ◽  
Percent Weight Loss ◽  
Baseline Body Weight ◽  
Baseline Characteristics ◽  
Overweight Or Obesity

Abstract Background: Semaglutide is a long-acting, subcutaneous (s.c.), glucagon-like peptide-1 analogue that is currently being investigated for obesity management in adults with overweight or obesity in the phase 3 STEP clinical trial program. Varying degrees of weight loss were observed with once-weekly s.c. semaglutide 2.4 mg in STEP 1, and a post-hoc analysis was conducted to investigate weight loss in subgroups of participants based on their baseline characteristics. Methods: STEP 1 was a randomized, double-blind, placebo-controlled, phase 3 trial (NCT03548935). 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, were randomized 2:1 to 68 weeks’ treatment with once-weekly s.c. semaglutide 2.4 mg or placebo, as adjunct to lifestyle intervention. A descriptive evaluation of categorical weight loss with semaglutide from baseline to week 68 (≥20%, 15-<20%, 10-<15%, 5-<10%) by baseline characteristics (age, sex, race [White, Asian, Black or African American, other], body weight, BMI, waist circumference, and glycemic status [normo-glycemia, pre-diabetes]) was conducted. Mean percent weight loss with semaglutide from baseline to week 68 was analyzed separately by sex (male, female) and baseline body weight (≥115 kg, 100-<115 kg, 90-<100 kg, <90 kg) using a mixed model for repeated measurements analysis with treatment, subgroup (of sex or baseline body weight), and the interaction between treatment and subgroup 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). Results: STEP 1 included 1,961 randomized participants (mean age 46 years, body weight 105.3 kg, BMI 37.9 kg/m2; 74.1% female). For categorical weight loss, the observed proportions of participants with ≥20%, 15-<20%, 10-<15%, and 5-<10% weight loss at week 68 were 34.8%, 19.9%, 20.0%, and 17.5% with semaglutide vs 2.0%, 3.0%, 6.8%, and 21.2% with placebo, respectively. The distribution of participants across weight loss groups did not appear to be affected by any baseline characteristics, except sex and baseline body weight. Mean percent weight loss at week 68 with semaglutide was greater among females than males, and in participants with lower vs higher baseline body weight. Sex and baseline body weight were independently associated with weight loss with semaglutide vs placebo at week 68 (p<0.001 for both tests for subgroup interactions). Conclusion: In STEP 1, weight loss with once-weekly s.c. semaglutide 2.4 mg was seen in all subgroups evaluated, and was generally not influenced by baseline characteristics. The exception was sex and baseline body weight; female sex and a low baseline body weight were associated with a greater response to semaglutide.

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.

scholarly journals Reduction of Cardio-Metabolic Risk and Body Weight through a Multiphasic Very-Low Calorie Ketogenic Diet Program in Women with Overweight/Obesity: A Study in a Real-World Setting

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1804
Author(s):  
Elena Tragni ◽  
Luisella Vigna ◽  
Massimiliano Ruscica ◽  
Chiara Macchi ◽  
Manuela Casula ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Waist Circumference ◽  
Real World ◽  
Metabolic Complications ◽  
Multi Centre Study ◽  
Low Calorie ◽  
Ketogenic Diets ◽  
Real World Setting ◽  
Overweight Or Obesity

Background: The prevention and treatment of obesity and its cardio-metabolic complications are relevant issues worldwide. Among lifestyle approaches, very low-calorie ketogenic diets (VLCKD) have been shown to lead to rapid initial weight loss, resulting in better long-term weight loss maintenance. As no information on VLCKD studies carried on in a real-world setting are available, we conducted this multi-centre study in a real-world setting, aiming at assessing the efficacy and the safety of a specific multiphasic VLCKD program in women with overweight or obesity. Methods: A multi-center, prospective, uncontrolled trial was conducted in 33 outpatient women (age range 27–60 y) with overweight or obesity (BMI: 30.9 ± 2.7 kg/m2; waist circumference: 96.0 ± 9.4 cm) who started a VLCKD dietary program (duration: 24 weeks), divided into four phases. The efficacy of VLCKD was assessed by evaluating anthropometric measures and cardiometabolic markers; liver and kidney function biomarkers were assessed as safety parameters. Results: The VLCKD program resulted in a significant decrease of body weight and BMI (−14.6%) and waist circumference (−12.4%). At the end of the protocol, 33.3% of the participants reached a normal weight and the subjects in the obesity range were reduced from 70% to 16.7%. HOMA-IR was markedly reduced from 3.17 ± 2.67 to 1.73 ± 1.23 already after phase 2 and was unchanged thereafter. Systolic blood pressure decreased after phase 1 (−3.5 mmHg) and remained unchanged until the end of the program. Total and LDL cholesterol and triglycerides were significantly reduced by VLCKD along with a significant HDL cholesterol increase. Liver, kidney and thyroid function markers did not change and remained within the reference range. Conclusions: The findings of a multi-center VLCKD program conducted in a real-world setting in a cohort of overweight/obese women indicate that it is safe and effective, as it results in a major improvement of cardiometabolic parameters, thus leading to benefits that span well beyond the mere body weight/adiposity reduction.

Effect of eprosartan on catecholamines and peripheral haemodynamics in subjects with insulin-induced hypoglycaemia

2005 ◽  
Vol 108 (2) ◽  
pp. 113-119 ◽  
Author(s):  
Marina CHRISTENSEN ◽  
Hans IBSEN ◽  
René WORCK
Keyword(s):  
Body Weight ◽  
Blood Pressure Monitoring ◽  
Animal Experiments ◽  
Plasma Renin ◽  
Fold Increase ◽  
Catecholamine Release ◽  
Repeated Measurements ◽  
Ang Ii ◽  
Double Blind ◽  
Pronounced Increase

ANG II (angiotensin II) facilitates catecholamine release from the adrenal medulla and neuronal NE (noradrenaline) release. Since animal experiments point to specific sympatho-inhibitory properties of the AT1 (ANG II type 1)-receptor blocker EPRO (eprosartan), the primary aim of this study was to clarify if EPRO inhibits sympathetic reactivity in humans as determined by the effect of EPRO on insulin-induced catecholamine release. Sixteen healthy male volunteers were randomized in a double-blind cross-over study to receive a single dose of EPRO (600 mg) compared with placebo, followed by insulin-induced hypoglycaemia [0.15 IU (international unit)/kg of body weight; intravenous bolus] on two study days 1 week apart. From baseline to the end of hypoglycaemia (170 min), the sympatho-adrenal reactivity was mapped by invasive continuous blood pressure monitoring and repeated measurements of FBF (forearm blood flow), arterial and venous concentrations of glucose, catecholamines [EPI (adrenaline) and NE (noradrenaline)], renin, ANG II and aldosterone. EPRO induced an 8–10-fold increase in plasma renin and ANG II concentrations compared with placebo. Plasma glucose decreased equally during placebo and EPRO from baseline 5.9 mmol/l to 1.9 mmol/l and 2.1 mmol/l respectively, inducing a 17-fold increase in arterial EPI concentration at peak. The AUC (area under the curve) during hypoglycaemia for arterial EPI concentrations was 314±48 nmol·min·l−1 in placebo compared with 254±26 nmol·min·l−1 following EPRO treatment (P=0.14). EPRO attenuated the corresponding AUC for the EPI-induced pulse pressure response (4670±219 mmHg·min in EPRO compared with 5004±266 mmHg·min in placebo; P=0.02). Moreover, EPRO caused a less pronounced increase in FBF compared with placebo (402±30 compared with 479±46 ml·100 g−1 of body weight; P=0.04). Musculocutaneous NE release was not affected by EPRO and the AUC for NE release was 51.69±15.5 pmol·min−1·100 g−1 of body weight in placebo compared with 39.35±18.2 pmol·min−1·100 g−1 of body weight after EPRO treatment (P=0.57). In conclusion, EPRO did not significantly inhibit sympathetic reactivity compared with placebo; however, it blunted the haemodynamic responses elicited by the sympatho-adrenal stimulation which only tended to be attenuated by this drug.

scholarly journals Effect of liraglutide on body weight and pain in patients with overweight and knee osteoarthritis: protocol for a randomised, double-blind, placebo-controlled, parallel-group, single-centre trial

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e024065 ◽  
Author(s):  
Henrik Gudbergsen ◽  
Marius Henriksen ◽  
Eva Ejlersen Wæhrens ◽  
Anders Overgaard ◽  
Henning Bliddal ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Knee Osteoarthritis ◽  
Controlled Trial ◽  
Single Centre ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Knee Oa ◽  
Parallel Group ◽  
Pain Subscale

IntroductionWith an increasing prevalence of citizens of older age and with overweight, the health issues related to knee osteoarthritis (OA) will intensify. Weight loss is considered a primary management strategy in patients with concomitant overweight and knee OA. However, there are no widely available and feasible methods to sustain weight loss in patients with overweight and knee OA. The present protocol describes a randomised controlled trial evaluating the efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide in a 3 mg/day dosing in patients with overweight and knee OA.Methods and analysis150 volunteer adult patients with overweight or obesity and knee OA will participate in a randomised, double-blind, placebo-controlled, parallel-group and single-centre trial. The participants will partake in a run-in diet intervention phase (week −8 to 0) including a low calorie diet and dietetic counselling. At week 0, patients will be randomised to either liraglutide 3 mg/day or liraglutide placebo 3 mg/day for 52 weeks as an add-on to dietetic guidance on re-introducing regular foods and a focus on continued motivation to engage in a healthy lifestyle. The co-primary outcomes are changes in body weight and the Knee Injury and Osteoarthritis Outcome Score pain subscale from week 0 to week 52.Ethics and disseminationThe trial has been approved by the regional ethics committee in the Capital Region of Denmark, the Danish Medicines Agency and the Danish Data Protection Agency. An external monitoring committee (The Good Clinical Practice Unit at Copenhagen University Hospitals) will oversee the trial. The results will be presented at international scientific meetings and through publications in peer-reviewed journals.Trial registration numbers2015-005163-16,NCT02905864, U1111-1171-4970Based on protocol versionV.6; 30 January 2017, 15:30 hours

scholarly journals Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults with Overweight or Obesity and Type 2 Diabetes Mellitus: A 54-Week Randomized Phase 2b Study

2021 ◽  
Author(s):  
Rajaa Nahra ◽  
Tao Wang ◽  
Kishore M. Gadde ◽  
Jan Oscarsson ◽  
Michael Stumvoll ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Body Weight ◽  
Ad Hoc ◽  
Open Label ◽  
Double Blind ◽  
Glucagon Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Design And Methods

<a><b>Objective: </b></a>Cotadutide, a <a>dual GLP-1 and glucagon receptor agonist</a>, is under development for nonalcoholic steatohepatitis (NASH) and type 2 diabetes. The effects of cotadutide on hepatic and metabolic parameters were evaluated in participants with overweight/obesity and type 2 diabetes. <p><b>Research Design and Methods:</b> In this phase 2b study, 834 adults with BMI ≥25kg/m<sup>2</sup> and type 2 diabetes inadequately controlled with metformin (glycated hemoglobin A1c [HbA1c] of 7.0%─10.5% [53─91 mmol/mol]) were randomized to double-blind cotadutide 100µg (n=100), 200µg (n=256), or 300µg (n=256), placebo (n=110), or open-label liraglutide 1.8mg (n=110), all administered subcutaneously (NCT03235050). Coprimary endpoints were changes in HbA1c and body weight at week 14.<b> </b>The originally randomized interventions were continued to week 54.<b> </b>Liver damage biomarkers and liver fibrosis algorithms were assessed.</p> <p><b>Results</b>: Cotadutide significantly decreased HbA1c and body weight at weeks 14 and 54 versus placebo (all <i>P</i><0.001). Improvements in lipid profile, aspartate aminotransferase and alanine aminotransferase levels, <a>PRO-C3 level, fibrosis-4 index</a>, and <a>nonalcoholic fatty liver disease fibrosis score</a> were observed with cotadutide 300µg versus placebo, but not with liraglutide. Weight loss with cotadutide 200µg was similar to liraglutide 1.8mg, and greater with cotadutide 300µg versus liraglutide 1.8mg. <a>The most common adverse events with cotadutide (nausea, 35%; vomiting, 17%) decreased over time. </a></p> <p><b>Conclusions: </b>Cotadutide treatment for 54 weeks improved glycemic control and weight loss in participants with overweight/obesity and type 2 diabetes. Ad hoc analyses demonstrated improvements in hepatic parameters and support further evaluation of cotadutide in NASH. </p>

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management

2021 ◽  
pp. 106002802110538
Author(s):  
Courtney L. Bradley ◽  
Sara M. McMillin ◽  
Andrew Y. Hwang ◽  
Christina H. Sherrill
Keyword(s):  
Weight Loss ◽  
Adverse Effects ◽  
Data Extraction ◽  
High Dose ◽  
Lifestyle Interventions ◽  
Double Blind ◽  
Study Selection ◽  
Patients With Diabetes ◽  
Glycemic Indices ◽  
Overweight Or Obesity

Objective To review the pharmacology, efficacy, and safety of high-dose once-weekly semaglutide for chronic weight management. Data Sources PubMed/MEDLINE and ClinicalTrials.gov were searched (inception to September 8, 2021) using keywords “semaglutide” and “obesity,” “weight,” “high dose,” “high-dose,” or “2.4.” Study Selection and Data Extraction Clinical trials with published results were included. Publications studying the oral or <2.4 mg formulation of semaglutide were excluded. Data Synthesis Four phase 3, multicenter, randomized, double-blind trials demonstrated efficacy of high-dose once-weekly semaglutide compared with placebo for weight loss. Study populations included patients with overweight or obesity (STEP 1, STEP 3, and STEP 4) or patients with diabetes and with overweight or obesity (STEP 2). Lifestyle interventions for diet and exercise were included for all participants. Weight loss from baseline was significant for all studies, and secondary outcomes demonstrated cardiometabolic improvements including waist circumference, systolic blood pressure, and lipid profiles. Gastrointestinal adverse effects were common, but the medication was otherwise well tolerated. Relevance to Patient Care and Clinical Practice High-dose semaglutide offers significant weight-lowering potential and favorable effects on cardiometabolic risk factors and glycemic indices. Clinicians and patients should consider the route and frequency of administration, adverse effect profile, and cost when choosing an antiobesity medication. The importance of concomitant lifestyle interventions should be emphasized. Conclusions High-dose once-weekly semaglutide can significantly reduce weight, and although gastrointestinal adverse effects were common, it is generally well tolerated.

Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

The Lancet ◽  
2010 ◽  
Vol 376 (9741) ◽  
pp. 595-605 ◽  
Author(s):  
Frank L Greenway ◽  
Ken Fujioka ◽  
Raymond A Plodkowski ◽  
Sunder Mudaliar ◽  
Maria Guttadauria ◽  
...  
Keyword(s):  
Weight Loss ◽  
Obese Adults ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo

Body weight response with anamorelin in advanced non-small cell lung cancer (NSCLC) patients with anorexia/cachexia: Pooled analysis of two phase III trials.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10097-10097 ◽  
Author(s):  
David Christopher Currow ◽  
Jennifer S. Temel ◽  
Amy Pickar Abernethy ◽  
John Friend ◽  
Ruben Giorgino
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Advanced Nsclc ◽  
Pooled Analysis ◽  
Phase Iii ◽  
P Value ◽  
Double Blind ◽  
Entire Study ◽  
Ghrelin Receptor ◽  
Nsclc Patients

10097 Background: Anorexia/cachexia commonly occurs in patients with advanced NSCLC and is associated with increased morbidity and mortality. In two randomized, double-blind, placebo-controlled phase 3 trials in NSCLC patients with cachexia, the ghrelin receptor agonist anamorelin was well tolerated and significantly increased body weight, lean and fat mass, and anorexia/cachexia symptom burden over 12 weeks compared to placebo (Temel J. Lancet Oncol. 2016). Since an involuntary weight loss of ≥ 5% is an established diagnostic criterion for cancer anorexia/cachexia, an analysis was conducted to assess the proportion of patients with ≥ 5% increase in body weight. Methods: NSCLC patients [ROMANA 1 (NCT01387269; N = 484) and ROMANA 2 (NCT01387282; N = 495)] with stage III/IV disease and cachexia (BMI < 20 kg/m2 or ≥ 5% weight loss during prior 6 months) were randomized 2:1 to receive 100 mg once daily oral anamorelin or placebo up to 12 weeks. A pooled analysis was conducted post-hoc in the modified intent-to-treat population (N = 829) to measure the proportion of patients with ≥ 5% increase in body weight at the end of study (or last observation carried forward since week 6 or 9). Results: The percentage of patients with ≥ 5% increase in body weight at the end of study was significantly higher in the anamorelin arm (N = 188/552, 34.1%) compared to placebo (N = 37/277; 13.4%). Among patients with BMI < 20kg/m2 at baseline (N = 182), 47.3% (N = 53/112) of anamorelin patients had a weight increase of ≥ 5% compared to 17.4% (N = 12/69) in the placebo arm. In both cases the nominal p-value was lower than 0.0001. Conclusions: Data from two published large pivotal studies in advanced NSCLC patients with anorexia/cachexia suggest that anamorelin treatment effect size on body weight is clinically relevant, as shown by the higher response rate achieved when the stringent cut-off of ≥ 5% weight gain was applied. The proportion of patients with BMI < 20kg/m2 that benefited from anamorelin treatment was greater than the proportion of patients who benefited in the entire study sample, suggesting that patients with more advanced cachexia may still benefit from anamorelin treatment. Clinical trial information: ROMANA 1: NCT01387269; ROMANA 2: NCT01387282.

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