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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 · 4,989 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 · 2,999 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 · 1,996 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 · 1,813 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 · 1,595 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 · 1,349 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 · 1,069 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 · 955 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 · 929 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 · 719 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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  14. Factors associated with weight loss response to GLP-1 analogues for obesity treatment: a retrospective cohort analysis

    Peter Squire, James Naude, Ali Zentner, et al. · 2025 · BMJ Open · 43 citations

    Objectives The response to glucagon-like peptide-1 (GLP-1) analogues for weight loss varies significantly. We investigated the anthropometric, demographic and clinical characteristics associated with total body weight loss (TBWL) from subcutaneous GLP-1 analogue therapy in patients with obesity in a real-world setting. Design Retrospective cohort analysis. Setting An urban, multidisciplinary obesity community clinic in Vancouver, Canada, from November 2018 to April 2021. Participants 483 adults with a body mass index (BMI) of ≧30 kg/m2 who had filled a new prescription for subcutaneous semaglutide or liraglutide, with at least 6-month follow-up, were included (mean follow-up: 17.3 months). I

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  15. Impact of Digital Engagement on Weight Loss Outcomes in Obesity Management Among Individuals Using GLP-1 and Dual GLP-1/GIP Receptor Agonist Therapy: Retrospective Cohort Service Evaluation Study

    Hans Johnson, David Huang, Vivian N. Liu, et al. · 2024 · Journal of Medical Internet Research · 25 citations

    Background Obesity is a global public health challenge. Pharmacological interventions, such as glucagon-like peptide-1 (GLP-1) receptor agonists (eg, semaglutide) and dual GLP-1/gastric inhibitory polypeptide receptor agonists (eg, tirzepatide), have led to significant weight loss among users. Digital health platforms offering behavioral support may enhance the effectiveness of these medications. Objective This retrospective service evaluation investigated the impact of engagement with an app-based digital weight loss program on weight loss outcomes among individuals using GLP-1 receptor agonists (semaglutide) and dual GLP-1/gastric inhibitory polypeptide receptor agonists (tirzepatide) in t

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  16. Rebound or Retention: A Meta-Analysis of Weight Regain After the Discontinuation of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Other Anti-obesity Drugs

    Ravi Teja Kolli, Sridevi Aoutla, Nirmal Jyothi, et al. · 2025 · Cureus · 19 citations

    Anti-obesity pharmacotherapies, such as glucagon-like peptide-1 (GLP-1) receptor agonists and orlistat, are effective for weight loss; however, weight regain following treatment discontinuation remains a major concern. This meta-analysis aimed to quantify the magnitude of weight regain after reaching peak weight loss, and to compare rebound effects across four commonly used agents: semaglutide, liraglutide, exenatide, and orlistat. A systematic search was conducted in PubMed (n = 498), Cochrane Library (n = 41), Scopus (n = 258), ScienceDirect (n = 248), and Web of Science (n = 158) from January 2010 to October 2024. After removing 153 duplicates, 950 records were screened. Following full-te

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  17. Weight Loss Efficacy of Tirzepatide Compared to Placebo or GLP-1 Receptor Agonists in Adults With Obesity or Overweight: A Meta-Analysis of Randomized Controlled Trials With ≥ 20 Weeks Treatment Duration

    Alhussain Khawaji, Abdulaziz A. Jaly, Hanan A. Bakri, et al. · 2025 · Journal of Obesity · 14 citations

    Introduction: Tirzepatide, a dual glucose‐dependent insulinotropic peptide (GIP) and glucagon‐like Peptide 1 (GLP‐1) analogue, is a novel medication with comparable pharmacological characteristics and has demonstrated promising weight reduction outcomes in its antidiabetic trials following the approval of liraglutide and semaglutide for long‐term weight control. Nonetheless, this efficacy has not been fully explored, so this meta‐analysis was aimed to measure the weight loss efficacy and safety of tirzepatide in adults with overweight or obesity.

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  18. Beyond Weight Loss: Optimizing GLP-1 Receptor Agonist Use in Children

    Hussein Zaitoon, A. Wauters, L. Rodriguez, et al. · 2025 · Children · 12 citations

    Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a transformative therapy for obesity and type 2 diabetes (T2D) in pediatric populations. This review synthesizes current evidence on efficacy, safety, and knowledge gaps in children and adolescents. Methods: A structured review of randomized controlled trials, extension studies, and mechanistic investigations evaluating GLP-1RAs in pediatric obesity and T2D was conducted. Outcomes of interest included body weight, BMI, body composition, glycemic control, and adverse events. Results: In adolescents, liraglutide and semaglutide consistently produce clinically meaningful reductions in BMI, body weight, a

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  19. Weight loss therapy and addiction: increased risk after bariatric surgery but reduced risk with GLP-1 receptor agonists.

    A. Scheen · 2025 · Diabetes & metabolism · 11 citations

    BACKGROUND Obesity is an increasing public health problem because of its high prevalence and associated morbidity and mortality. Two weight-loss strategies are currently used, either bariatric surgery or pharmacological therapy with glucagon-like peptide-1 receptor agonists (GLP-1RAs). Preclinical studies in rodents suggested an increased risk of additive disorders after bariatric surgery contrasting with a reduced risk with GLP-1RAs. METHODS An extensive literature search to detect clinical studies that investigated the prevalence of addictive disorders (food addiction, alcohol abuse, smoking, cannabis, cocaine, opioid use) following bariatric surgery or GLP-1RA therapy in obese patients.

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  21. Comparative Safety of GLP-1/GIP Co-Agonists Versus GLP-1 Receptor Agonists for Weight Loss in Patients with Obesity or Overweight: A Systematic Review

    Zeyu Xie, Zhuoru Liang, Yilin Xie, et al. · 2025 · Diabetes, Metabolic Syndrome and Obesity · 10 citations

    Purpose Tirzepatide, a dual GLP-1/GIP agonist, shows promise for weight loss, but its safety compared to GLP-1 receptor agonists requires (liraglutide, semaglutide) clarification for clinical decision-making. This systematic review evaluates their safety profiles in patients with obesity or overweight. Methods We conducted a PRISMA-compliant systematic review (PROSPERO: CRD42024576314) of RCTs from PubMed, Embase, and Cochrane (inception to August 20, 2024). Adults with BMI ≥27 kg/m² (≥25 kg/m² for Asians) receiving GLP-1/GIP dual agonists (tirzepatide 10 or 15 mg) and GLP-1 receptor agonists (semaglutide 2.4 mg and liraglutide 3.0 mg) were included. Network meta-analysis (NMA) was conducted

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  22. 2FA-Platform Generates Dual Fatty Acid-Conjugated GLP-1 Receptor Agonist TE-8105 with Enhanced Diabetes, Obesity, and NASH Efficacy Compared to Semaglutide

    Mun-Teng Wong, Pei-Hsuan Lin, Wei-Chen Lin, et al. · 2025 · Journal of Medicinal Chemistry · 10 citations

    Conjugating two fatty acids (2FAs) to peptide drugs can improve pharmacokinetics and therapeutic effects. However, optimizing FA spacing, chain combination, and attachment site to simultaneously enhance albumin binding and drug efficacy remains challenging. We introduce a multiarm linker technology enabling precise control of 2FA spacing, composition, and attachment. By applying this technology to a modified glucagon-like peptide-1 (GLP-1) and screening various 2FA-GLP-1 conjugates differing in linkage, linker, and FA properties for improved albumin affinity, pharmacokinetics, and pharmacodynamics, TE-8105 emerged as a promising candidate. TE-8105 outperformed semaglutide, showing improved l

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  23. Interest in Treatment with GLP-1 Receptor Agonists for the Management of Insufficient Weight Loss or Weight Regain After Bariatric Surgery

    Hussein Abdallah, W. Klink, J. Derienne, et al. · 2025 · Obesity Surgery · 10 citations

    Bariatric surgery (BS) is the most effective treatment for severe obesity, but a significant proportion of patients experience insufficient weight loss (IWL) or weight regain. Glucagon-like peptide-1 receptor agonists (arGLP-1) have emerged as a promising adjunctive therapy for managing these suboptimal outcomes. This study evaluates the efficacy and safety of arGLP-1 in patients with IWL or WR after BS. A retrospective analysis was conducted on 100 patients who underwent BS (96 sleeve gastrectomy, 4 gastric bypass) and received arGLP-1 therapy (semaglutide or dulaglutide) for IWL (defined as < 50% excess weight loss (EWL) from baseline), and WR (a ≥ 10 kg increase from the nadir weight post

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  24. Weight Loss That Lasts: Reviewing the Long-Term Impact of GLP-1 Receptor Agonists

    Marwah Shah, Ahmad Mohammad, Rabia Bashir Ahmed Samejo, et al. · 2025 · Cureus · 8 citations

    This systematic review evaluates the long-term efficacy and safety of GLP-1 receptor agonists in the management of obesity, focusing on data from high-quality randomized controlled trials published between 2018 and 2025. This review synthesizes findings from studies assessing agents such as semaglutide, liraglutide, tirzepatide, and exenatide in diverse populations, including adults with and without type 2 diabetes and adolescents with severe obesity. Most studies demonstrated sustained weight loss and favorable glycemic control over treatment durations of 40-120 weeks. Additionally, the agents showed generally acceptable safety profiles, with gastrointestinal side effects being the most fre

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