Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial

O’Neil, Patrick M.; Birkenfeld, Andreas L.; McGowan, Barbara; Mosenzon, Ofri; Pedersen, Sue D.; Wharton, Sean; Carson, Claire; Jepsen, Cecilie H.; Kabisch, Maria; Wilding, John

doi:10.1016/s0140-6736(18)31773-2

Cited by 559 publications

(550 citation statements)

References 25 publications

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“…163 For lixisenatide treatment, 56-60% of patients developed anti-lixisenatide antibodies after starting treatment, and development of antilixisenatide antibodies also appears to be of little clinical relevance. 244 Semaglutide (0.05 mg daily) and semaglutide (0.4 mg daily) provided a weight reduction of 6.8% and 16.2%, respectively, in comparison to liraglutide (3 mg daily) of 8.3% and placebo of 2.3%. 171,[198][199][200] Weight reduction.…”

Section: Clinical Application Of Gip and Glp-1 In Obesity And Diabetesmentioning

confidence: 97%

“…197 The GLP-1R agonists based on native GLP-1 peptide generally have much lower antibody responses (8-9% for liraglutide; 3-7% for albiglutide; 1-3% for dulaglutide; and 1.7% for semaglutide), and these antibodies do not lead to a clinically relevant effect on glycemic control. 244 GLP-1R agonists in treating prediabetes. GLP-1 has a well-documented effect on satiety.…”

Section: Clinical Application Of Gip and Glp-1 In Obesity And Diabetesmentioning

confidence: 99%

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Incretins in obesity and diabetes

Chia

Egan

2019

Annals of the New York Academy of Sciences

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Incretins are hormones secreted from enteroendocrine cells after nutrient intake that stimulate insulin secretion from β cells in a glucose‐dependent manner. Glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) are the only two known incretins. Dysregulation of incretin secretion and actions are noted in diseases such as obesity and diabetes. In this review, we first summarize our traditional understanding of the physiology of GIP and GLP‐1, and our current knowledge of the relationships between GIP and GLP‐1 and obesity and diabetes. Next, we present the results from major randomized controlled trials on the use of GLP‐1 receptor agonists for managing type 2 diabetes, and emerging data on treating obesity and prediabetes. We conclude with a glimpse of the future with possible complex interactions between nutrients, gut microbiota, the endocannabinoid system, and enteroendocrine cells.

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Section: Clinical Application Of Gip and Glp-1 In Obesity And Diabetesmentioning

confidence: 97%

Section: Clinical Application Of Gip and Glp-1 In Obesity And Diabetesmentioning

confidence: 99%

Incretins in obesity and diabetes

Chia

Egan

2019

Annals of the New York Academy of Sciences

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“…In 2023 onward, 15% of eligible treatment‐naïve individuals and patients already on AOM would initiate next‐generation AOM. AOM efficacy was kept at 8.9% from 2019 to 2023 and was increased to 14% beginning in the year 2023, consistent with existing evidence of next‐generation AOM on the horizon . Finally, in scenario 4 (30% uptake, next generation), we kept all model components similar to scenario 3 (15% uptake, next generation), except annual treatment uptake was increased to 30% beginning in 2023 with the availability of more efficacious AOM.…”

Section: Methodsmentioning

confidence: 99%

The Societal Value of Broader Access to Antiobesity Medications

Kabiri¹,

Ward²,

Ramasamy

et al. 2019

Obesity

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Objective Obesity and its complications place an enormous burden on society. Yet antiobesity medications (AOM) are prescribed to only 2% of the eligible population, even though few individuals can sustain weight loss using other strategies alone. This study estimated the societal value of greater access to AOM. Methods By using a well‐established simulation model (The Health Economics Medical Innovation Simulation), the societal value of AOM for the cohort of Americans aged ≥ 25 years in 2019 was quantified. Four scenarios with differential uptake among the eligible population (15% and 30%) were modeled, with efficacy from current and next‐generation AOM. Societal value was measured as monetized quality of life, productivity gains, and savings in medical spending, subtracting the costs of AOM. Results For the 217 million Americans aged ≥ 25 years, AOM generated $1.2 trillion in lifetime societal value under a conservative scenario (15% annual uptake using currently available AOM). The introduction of next‐generation AOM increased societal value to $1.9 to $2.5 trillion, depending on uptake. Finally, societal value was higher for younger individuals and Black and Hispanic individuals compared with White individuals. Conclusions This study suggests that AOM provide substantial gains to patients and society. Policies promoting broader clinical access to and use of AOM warrant consideration to reach national goals to reduce obesity.

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“…Even for those that respond to treatment, a mean weight loss of 8% is not enough to address higher grades of obesity, and is not competitive with the typical weight loss from bariatric surgery of 20% or so . Newer GLP1R agonists such as Semaglutide possess better efficacy in terms of glycaemic improvement and weight loss (with mean reductions in weight of 6%‐14%) . Nevertheless, to achieve better and titratable outcomes, for example 15%‐20% weight loss, it will be necessary to exploit the power of combination therapy with other gut hormones.…”

Section: Glp‐1 Action Clinical Applications and Limitationsmentioning

confidence: 99%

Cracking the combination: Gut hormones for the treatment of obesity and diabetes

Αλεξιάδου

Anyiam

Tan

2019

J Neuroendocrinology

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Obesity and type 2 diabetes are a veritable global pandemic. There is an imperative to develop new therapies for these conditions that can be delivered at scale to patients, which deliver effective and titratable weight loss, amelioration of diabetes, prevention of diabetic complications and improvements in cardiovascular health. Although agents based on glucagon‐like peptide‐1 (GLP‐1) are now in routine use for diabetes and obesity, the limited efficacy of such drugs means that newer agents are required. By combining the effects of GLP‐1 with other gut and metabolic hormones such as glucagon (GCG), oxyntomodulin, glucose‐dependent insulinotropic peptide (GIP) and peptide YY (PYY), we may obtain improved weight loss, increased energy expenditure and improved metabolic profiles. Drugs based on dual agonism of GLP1R/GCGR and GLP1R/GIPR are being actively developed in clinical trials. Triple agonism, for example with GLPR1/GCGR/GIPR unimolecular agonists or using GLP‐1/oxyntomodulin/PYY, is also being explored. Multi‐agonist drugs seem set to deliver the next generation of therapies for diabetes and obesity soon.

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Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial

Cited by 559 publications

References 25 publications

Incretins in obesity and diabetes

Incretins in obesity and diabetes

The Societal Value of Broader Access to Antiobesity Medications

Cracking the combination: Gut hormones for the treatment of obesity and diabetes

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