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Research papers on GLP-1 drugs and weight loss

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  1. Once-Weekly Semaglutide in Adults with Overweight or Obesity

    John Wilding, Rachel L. Batterham, Salvatore Calanna, et al. · 2021 · New England Journal of Medicine · 4,935 citations

    BACKGROUND: Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed. METHODS: In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end

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  2. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes

    A. Michael Lincoff, Kirstine Brown‐Frandsen, Helen M. Colhoun, et al. · 2023 · New England Journal of Medicine · 2,956 citations

    BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to reduce the risk of adverse cardiovascular events in patients with diabetes. Whether semaglutide can reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes is unknown. METHODS: In a multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial, we enrolled patients 45 years of age or older who had preexisting cardiovascular disease and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 27 or greater but no history of diabetes. Patients were randomly assigned in a 1:1 ratio to receive once-weekly subcu

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  3. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis

    Philip N. Newsome, Kristine Buchholtz, Kenneth Cusi, et al. · 2020 · New England Journal of Medicine · 1,985 citations

    BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a common disease that is associated with increased morbidity and mortality, but treatment options are limited. The efficacy and safety of the glucagon-like peptide-1 receptor agonist semaglutide in patients with NASH is not known. METHODS: We conducted a 72-week, double-blind phase 2 trial involving patients with biopsy-confirmed NASH and liver fibrosis of stage F1, F2, or F3. Patients were randomly assigned, in a 3:3:3:1:1:1 ratio, to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg or corresponding placebo. The primary end point was resolution of NASH with no worsening of fibrosis. The confirmatory secondary end

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  4. Glucagon-like peptide 1 (GLP-1)

    Timo D. Müller, Brian Finan, Stephen R. Bloom, et al. · 2019 · Molecular Metabolism · 1,810 citations

    BACKGROUND: The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent β-cell proliferation. GLP-1 also has cardio- and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability. Biochemically modified for enhanced potency and sustained action, GLP-1 receptor agonists are successfully in clinical use for the treatment of type-2 diabetes, and seve

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  5. GLP-1 receptor agonists in the treatment of type 2 diabetes – state-of-the-art

    Michael A. Nauck, Daniel R. Quast, Jakob Wefers, et al. · 2020 · Molecular Metabolism · 1,592 citations

    GLP-1 receptor agonists (GLP-1 RAs) with exenatide b.i.d. first approved to treat type 2 diabetes in 2005 have been further developed to yield effective compounds/preparations that have overcome the original problem of rapid elimination (short half-life), initially necessitating short intervals between injections (twice daily for exenatide b.i.d.). To summarize current knowledge about GLP-1 receptor agonist. At present, GLP-1 RAs are injected twice daily (exenatide b.i.d.), once daily (lixisenatide and liraglutide), or once weekly (exenatide once weekly, dulaglutide, albiglutide, and semaglutide). A daily oral preparation of semaglutide, which has demonstrated clinical effectiveness close to

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

    Domenica Rubino, Domenica Rubino, Niclas Abrahamsson, et al. · 2021 · JAMA · 1,345 citations

    Importance: The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown. Objective: To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly. Design, Setting, and Participants: Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (

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

    Thomas A. Wadden, Timothy S. Bailey, Liana K. Billings, et al. · 2021 · JAMA · 1,063 citations

    Importance: Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches. Objective: To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity. Design, Setting, and Participants: Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27)

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  8. The Discovery and Development of Liraglutide and Semaglutide

    Lotte Bjerre Knudsen, Jesper Lau · 2019 · Frontiers in Endocrinology · 945 citations

    The discovery of glucagon-like peptide-1 (GLP-1), an incretin hormone with important effects on glycemic control and body weight regulation, led to efforts to extend its half-life and make it therapeutically effective in people with type 2 diabetes (T2D). The development of short- and then long-acting GLP-1 receptor agonists (GLP-1RAs) followed. Our article charts the discovery and development of the long-acting GLP-1 analogs liraglutide and, subsequently, semaglutide. We examine the chemistry employed in designing liraglutide and semaglutide, the human and non-human studies used to investigate their cellular targets and pharmacological effects, and ongoing investigations into new applicatio

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

    Domenica M. Rubino, Frank L. Greenway, Usman Khalid, et al. · 2022 · JAMA · 922 citations

    Importance: Phase 3 trials have not compared semaglutide and liraglutide, glucagon-like peptide-1 analogues available for weight management. Objective: To compare the efficacy and adverse event profiles of once-weekly subcutaneous semaglutide, 2.4 mg, vs once-daily subcutaneous liraglutide, 3.0 mg (both with diet and physical activity), in people with overweight or obesity. Design, Setting, and Participants: Randomized, open-label, 68-week, phase 3b trial conducted at 19 US sites from September 2019 (enrollment: September 11-November 26) to May 2021 (end of follow-up: May 11) in adults with body mass index of 30 or greater or 27 or greater with 1 or more weight-related comorbidities, without

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  10. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial

    W. Timothy Garvey, Rachel L. Batterham, Meena Bhatta, et al. · 2022 · Nature Medicine · 844 citations

    Abstract The STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes. The co-primary endpoints were the percentage change in body weight and achievement of weight loss of ≥5% at week 104. Efficacy was assessed among all randomized participants regardless of treatment discontinuation or rescue intervention. From 5 October 2018 to 1 February 2019, 304 participants were randomly assigned to semaglutide 2.4 mg (n = 152) or placebo (n = 152), 92.8% of whom completed the trial (attended t

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  12. Obesity Management in Adults

    Arielle Elmaleh-Sachs, Jessica L. Schwartz, Carolyn T. Bramante, et al. · 2023 · JAMA · 709 citations

    Importance: Obesity affects approximately 42% of US adults and is associated with increased rates of type 2 diabetes, hypertension, cardiovascular disease, sleep disorders, osteoarthritis, and premature death. Observations: A body mass index (BMI) of 25 or greater is commonly used to define overweight, and a BMI of 30 or greater to define obesity, with lower thresholds for Asian populations (BMI ≥25-27.5), although use of BMI alone is not recommended to determine individual risk. Individuals with obesity have higher rates of incident cardiovascular disease. In men with a BMI of 30 to 39, cardiovascular event rates are 20.21 per 1000 person-years compared with 13.72 per 1000 person-years in m

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  16. 847-P: ASC47, a Muscle-Preserving Weight Loss Drug Candidate for Obesity, in Combination with Semaglutide, Demonstrated Superior Weight Loss to Semaglutide Monotherapy in a Preclinical Model

    JINZI JASON WU, CHENGFEI WU · 2025 · Diabetes · 2 citations

    Introduction and Objective: ASC47 (selective THR-β agonist) is an adipose-targeted, once-monthly subcutaneously (SQ) injected, muscle-preserving weight loss drug candidate for the treatment of obesity, discovered and developed in-house at Ascletis. This study in diet-induced obese (DIO) mice demonstrated a powerful synergy in weight loss and muscle preservation when combining ASC47 and semaglutide. Methods: C57BL/6J mice were fed a high-fat diet for 16 weeks and received different treatments for 28 days. Body weight and food intake were recorded daily. Body composition was assessed by EchoMRI weekly. Results: ASC47 low dose combination 1 demonstrated superior we

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  19. 1050-P: Revolutionary GLP-1 Weight Loss Medicine Semaglutide—To Cover or Not to Cover?

    WENHAO LU, AMELIA XIE, YIMEI YOU · 2025 · Diabetes

    Introduction and Objective: We created a data-driven prioritizing system to determine which groups of patients benefit most by insurance coverage of Semaglutide based on short- and long-term cost effectiveness in managing obesity and related chronic diseases. This prioritizing model will enhance societal health outcomes and promote equitable access compared to current affordability-based coverage models. Methods: This study uses a retrospective cohort design with CDC survey data from 2019-2023. We analyzed the prevalence of obesity-related diseases across different weight groups to simulate the potential effectiveness of Semaglutide in managing chronic conditions. Correlation

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