Once-Weekly Semaglutide in Adults with Overweight or Obesity

New England Journal of Medicine, Год журнала: 2021, Номер 384(11), С. 989 - 1002

Опубликована: Фев. 10, 2021

Obesity is a global health challenge with few pharmacologic options. Whether adults obesity can achieve weight loss once-weekly semaglutide at dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed.

Язык: Английский

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Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity

JAMA, Год журнала: 2021, Номер 325(14), С. 1414 - 1414

Опубликована: Март 23, 2021

The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people overweight or obesity is unknown.To compare continued once-weekly subcutaneous 2.4 mg, switch to placebo for (both lifestyle intervention) adults after 20-week run-in semaglutide titrated mg weekly.Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites 10 countries from June 2018 March 2020 body mass index least 30 (or ≥27 ≥1 weight-related comorbidity) and without diabetes.A total 902 participants received during run-in. After 20 weeks (16 dose escalation; 4 dose), 803 (89.0%) who reached the 2.4-mg/wk were randomized (2:1) 48 (n = 535) switched 268), plus intervention both groups.The primary end point was percent change week 68; confirmatory secondary points changes waist circumference, systolic blood pressure, physical functioning (assessed using Short Form 36 Version 2 Health Survey, Acute [SF-36]).Among completed period (with mean 10.6%) (mean age, 46 [SD, 12] years; 634 [79%] women; weight, 107.2 kg 22.7 kg]), 787 (98.0%) trial 741 (92.3%) treatment. With 68 -7.9% +6.9% (difference, -14.8 [95% CI, -16.0 -13.5] percentage points; P < .001). Waist circumference (-9.7 cm -10.9 -8.5 cm]), pressure (-3.9 mm Hg -5.8 -2.0 Hg]), SF-36 score (2.5 1.6-3.3]) also improved (all Gastrointestinal events reported 49.1% 26.1% placebo; similar proportions discontinued because adverse (2.4%) (2.2%).Among once weekly, maintaining compared switching resulted over following weeks.ClinicalTrials.gov Identifier: NCT03548987.

Язык: Английский

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Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity

JAMA, Год журнала: 2021, Номер 325(14), С. 1403 - 1403

Опубликована: Фев. 24, 2021

Importance

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

Objective

To compare effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for management as an adjunct to intensive behavioral therapy initial low-calorie diet adults

Design, Setting, Participants

Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites US from August 2018 April 2020 without diabetes (N = 611) either (body mass index ≥27) plus least 1 comorbidity obesity ≥30).

Interventions

Participants were randomized (2:1) (n 407) 204), both combined a first 8 weeks (ie, 30 counseling visits) during 68 weeks.

Main Outcomes Measures

The co–primary end points percentage change body 5% more baseline by week 68. Confirmatory secondary included losses 10% 15% weight.

Results

Of 611 participants (495 women [81.0%], mean age 46 years [SD, 13], 105.8 kg 22.9], 38.0 6.7]), 567 (92.8%) completed trial, 505 (82.7%) receiving treatment trial end. At 68, estimated was –16.0% semaglutide –5.7% (difference, −10.3 [95% CI, −12.0 −8.6];P < .001). More treated lost (86.6% 47.6%, respectively;P A higher proportion group achieved (75.3% 27.0% 55.8% 13.2%, Gastrointestinal adverse events frequent (82.8%) (63.2%). Treatment discontinued owing these 3.4% 0% participants.

Conclusions Relevance

Among obesity, compared placebo, used diet, resulted significantly greater Further research is needed assess durability findings.

Trial Registration

ClinicalTrials.gov Identifier:NCT03611582

Язык: Английский

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Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes

JAMA, Год журнала: 2022, Номер 327(2), С. 138 - 138

Опубликована: Янв. 11, 2022

InvestigatorsIMPORTANCE Phase 3 trials have not compared semaglutide and liraglutide, glucagon-like peptide-1 analogues available for weight management.OBJECTIVE To compare the efficacy adverse event profiles of once-weekly subcutaneous semaglutide, 2.4 mg, vs once-daily 3.0 mg (both with diet physical activity), in people overweight or obesity.DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label, 68-week, phase 3b trial conducted at 19 US sites from September 2019 (enrollment: 11-November 26) to May 2021 (end follow-up: 11) adults body mass index 30 greater 27 1 more weight-related comorbidities, without diabetes (N = 338).INTERVENTIONS Participants were randomized (3:1:3:1) receive (16-week escalation; n 126), matching placebo, (4-week 127), plus activity.Participants unable tolerate could 1.7 mg; participants liraglutide discontinued treatment restart 4-week titration.Placebo groups pooled (n 85). MAIN OUTCOMES MEASURESThe primary end point was percentage change weight, confirmatory secondary points achievement 10% more, 15% 20% loss, assessed week 68.Semaglutide comparisons active double-blinded against matched placebo groups.Comparisons treatments supportive points. RESULTSOf 338 (mean [SD] age, 49 [13] years; 265 women [78.4%]; mean 104.5 [23.8] kg; index, 37.5 [6.8]), 319 (94.4%) completed trial, 271 (80.2%) treatment.The baseline -15.8% -6.4% (difference, -9.4 [95% CI, -12.0 -6.8]; P < .001);weight -1.9%.Participants had significantly odds achieving loss (70.9% 25.6% [odds ratio, 6.3 {95% 3.5 11.2}], 55.6% 12.0% 7.9 4.1 15.4}], 38.5% 6.0% 8.2 19.1}], respectively; all .001).Proportions discontinuing any reason 13.5% 27.6% liraglutide.Gastrointestinal events reported by 84.1% 82.7% liraglutide.CONCLUSIONS RELEVANCE Among obesity diabetes, added counseling activity, resulted 68 weeks.

Язык: Английский

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Once-Weekly Semaglutide in Adolescents with Obesity

New England Journal of Medicine, Год журнала: 2022, Номер 387(24), С. 2245 - 2257

Опубликована: Ноя. 2, 2022

A once-weekly, 2.4-mg dose of subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist, is used to treat obesity in adults, but assessment the drug adolescents has been lacking.

Язык: Английский

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GLP-1 physiology informs the pharmacotherapy of obesity

Molecular Metabolism, Год журнала: 2021, Номер 57, С. 101351 - 101351

Опубликована: Окт. 8, 2021

Glucagon-like peptide-1 receptor agonists (GLP1RA) augment glucose-dependent insulin release and reduce glucagon secretion gastric emptying, enabling their successful development for the treatment of type 2 diabetes (T2D). These agents also inhibit food intake body weight, fostering investigation GLP1RA obesity. Here I discuss physiology (GLP-1) action in control animals humans, highlighting importance gut vs. brain-derived GLP-1 feeding weight. The widespread distribution function multiple (GLP1R) populations central autonomic nervous system are outlined, pathways controlling energy expenditure preclinical studies reduction both humans is highlighted. relative contributions vagal afferent GLP1R+ physiological anorectic response to compared reviewed. Key data two obesity therapy (liraglutide 3 mg daily semaglutide 2.4 once weekly) discussed. Finally, emerging potentially supporting combination with additional peptide epitopes unimolecular multi-agonists, as well fixed-dose therapies, actions weight highly conserved obese adolescents adults. well-defined mechanisms through a single G protein-coupled receptor, together extensive safety database people T2D, provide reassurance surrounding long-term use these co-morbidities. may be effective conditions associated obesity, such cardiovascular disease non-alcoholic steatohepatitis (NASH). Progressive improvements efficacy suggest that GLP-1-based therapies soon rival bariatric surgery viable options its complications.

Язык: Английский

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GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects

Frontiers in Endocrinology, Год журнала: 2021, Номер 12

Опубликована: Авг. 23, 2021

Glucagon like peptide-1 (GLP-1) is an incretin secretory molecule. GLP-1 receptor agonists (GLP-1RAs) are widely used in the treatment of type 2 diabetes (T2DM) due to their attributes such as body weight loss, protection islet β cells, promotion cell proliferation and minimal side effects. Studies have found that GLP-1R distributed on pancreatic other tissues has multiple biological effects, reducing neuroinflammation, promoting nerve growth, improving heart function, suppressing appetite, delaying gastric emptying, regulating blood lipid metabolism fat deposition. Moreover, GLP-1RAs neuroprotective, anti-infectious, cardiovascular protective, metabolic regulatory exhibiting good application prospects. Growing attention been paid relationship between tumorigenesis, development prognosis patient with T2DM. Here, we reviewed therapeutic effects possible mechanisms action nervous, cardiovascular, endocrine systems correlation metabolism, tumours diseases.

Язык: Английский

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Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial

The Lancet, Год журнала: 2021, Номер 397(10286), С. 1736 - 1748

Опубликована: Апрель 23, 2021

Язык: Английский

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Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial

The Lancet, Год журнала: 2023, Номер 402(10403), С. 705 - 719

Опубликована: Июнь 26, 2023

Язык: Английский

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Weight Loss and Maintenance Related to the Mechanism of Action of Glucagon-Like Peptide 1 Receptor Agonists

Advances in Therapy, Год журнала: 2021, Номер 38(6), С. 2821 - 2839

Опубликована: Май 11, 2021

Obesity is a chronic disease associated with many complications. Weight loss of 5–15% can improve obesity-related Despite the benefits weight reduction, there are challenges in losing and maintaining long-term loss. Pharmacotherapy help people obesity achieve maintain their target loss, thereby reducing risk The prevalence USA has been increasing over past few decades, despite availability approved anti-obesity medications (AOMs), may not be accessing or receiving treatment at levels consistent prevalence. Reasons for low initiation use AOMs include reluctance public health medical organizations to recognize as disease, lack reimbursement, provider inexperience, misperceptions about efficacy safety available treatments. This article aims inform primary care providers mechanism action one class AOMs, glucagon-like peptide 1 receptor agonists (GLP-1RAs), longer-term maintenance this class. GLP-1RA therapy was initially developed treat type 2 diabetes. Owing effectiveness body weight, once-daily subcutaneous administration liraglutide 3.0 mg approved, once-weekly semaglutide 2.4 being investigated phase III trials, management. Considerations regarding adverse effects contraindications different drug classes provided guide decision-making when considering pharmacotherapy management patients obesity. growing issue that increases developing heart diabetes, osteoarthritis. reduce these problems but, this, remain high. Achieving challenging individuals. There therefore need some take them lose prevent regain. Glucagon-like (GLP-1RAs) medication originally but now used because they effective helping weight. One GLP-1RA, liraglutide, obesity, another, semaglutide, clinical trials. GLP-1RAs work by appetite feelings hunger, slowing release food from stomach, fullness after eating. Most tolerate well. most common side (nausea, vomiting, diarrhea) usually mild occur first weeks treatment, time. Because difficulties face lifelong needed. In were well tolerated regain, good option control lowering patients' chances serious problems.

Язык: Английский

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