Plain Language Summary
This systematic review comprehensively evaluated approved weight loss drugs with emphasis on GLP-1 receptor agonists including semaglutide. The analysis covered efficacy in managing cardiometabolic comorbidities associated with obesity, including type 2 diabetes, hypertension, and cardiovascular disease.
Abstract
BACKGROUND: Obesity is a worldwide health concern linked to cardiometabolic comorbidities such as type 2 diabetes, hypertension, dyslipidemia, and heart disease. The management of obesity using pharmacotherapy, especially with GLP-1 receptor agonists and dual incretin agents, has proven successful not only for weight loss but also for gaining control of the metabolic components of the disease. Thus, it is pertinent to analyse the GLP-1-based anti-obesity medications to examine cardiometabolic efficacy and safety using weight loss, glycemic control, cardiometabolic, gastro-intestinal tolerability, and serious adverse events as the primary variables.
METHODS: The systematic review, according to the PRISMA 2020 guidelines, analyzed the GLP-1-based anti-obesity pharmacotherapies. Five databases were utilized to extract information from research studies related to the demographic and procedural framework, weight loss, cardiometabolic efficacy, and safety.
RESULTS: A total of 15 studies evaluated GLP-1-based and related anti-obesity therapies, including semaglutide, liraglutide, tirzepatide, dulaglutide, and dual GIP/GLP-1 receptor agonists. Participants were predominantly female (up to 79.3%), with mean age 22.4-59.8 years, BMI 29.3-43.0 kg/m², and common comorbidities including hypertension, dyslipidemia, type 2 diabetes, cardiovascular disease, metabolic syndrome, OSA, MASLD, insulin resistance, and PCOS. Weight loss was dose-dependent: semaglutide 2.4 mg/wk. -14.9% to -15.2%, tirzepatide 15-18.5%, liraglutide -8.8-11%, dulaglutide -1.3-2.0%, and dual GIP/GLP-1 therapy up to 21.5%. Glycemic and cardiometabolic improvements included HbA1c reductions up to -1.78%, SBP reductions -5.28 to -7.8 mmHg, and LDL-C decreases up to -11 mg/dL. Gastrointestinal adverse events were common (nausea 14.7-62%, vomiting 3-30.3%, diarrhoea 5-34.9%), while serious events, pancreatitis, and gallbladder complications were rare, with treatment discontinuation generally <15%.
CONCLUSION: GLP-1-based and dual GIP/GLP-1 therapies provide substantial, dose-dependent weight loss with additional cardiometabolic benefits. They are generally well tolerated, with mostly mild gastrointestinal adverse events and rare serious complications, supporting their efficacy and safety in managing obesity.
Authors
Gunasekaran, Praveen; Inban, Pugazhendi; Agrawal, Ashita; Thai, Andy; Aravazhi, Prasanna Sakthi; Tariq, Halla; Prajjwal, Priyadarshi; John, Jobby