Approved weight loss drugs for obesity with a thorough emphasis on GLP-1 agonist medications: A systematic review.
This systematic review, conducted according to PRISMA 2020 guidelines, synthesized evidence from 15 studies evaluating GLP-1 receptor agonist and dual incretin-based pharmacotherapies for obesity management, including semaglutide, liraglutide, tirzepatide, dulaglutide, and dual GIP/GLP-1 receptor agonists. Study participants were predominantly female (up to 79.3%), ranging in mean age from 22.4 to 59.8 years, with BMIs between 29.3 and 43.0 kg/m², and frequent comorbidities such as type 2 diabetes, hypertension, dyslipidemia, and cardiovascular disease. The review found that weight loss was dose-dependent across agents, with dual GIP/GLP-1 therapy showing the greatest reductions. Cardiometabolic outcomes included reductions in HbA1c, systolic blood pressure, and LDL cholesterol across therapies. Gastrointestinal adverse events — particularly nausea, vomiting, and diarrhea — were commonly reported but generally mild, while serious events such as pancreatitis and gallbladder complications were rare. Treatment discontinuation rates were described as generally low. Limitations include the heterogeneity of included studies, variability in populations, and the review's reliance on previously published trial data rather than original participant-level analysis.
Why this grade: This is a systematic review synthesizing findings from 15 existing studies rather than generating new primary human data, so evidence strength is classified at the review level.
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 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.
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