Summary

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• This summary is based on the review of 57 systematic review(s)/meta-analysis(es). ^[1-57]
• Subcutaneous semaglutide significantly reduced systolic blood pressure by -3.71 mmHg and diastolic blood pressure by -1.10 mmHg, with more pronounced effects in patients without diabetes, those with a body mass index (BMI) > 35 kg/m², or those achieving substantial weight loss. Oral semaglutide showed similar reductions in systolic blood pressure (-2.50 mmHg). Additionally, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), including semaglutide, reduced major adverse cardiovascular events (MACE) (odds ratio (OR): 0.79), all-cause mortality (OR: 0.80), and myocardial infarction (OR: 0.72).
• Semaglutide led to significant weight loss compared to placebo and other GLP-1 RAs, with subcutaneous semaglutide (2.4 mg) and oral semaglutide showing greater efficacy, particularly in patients without type 2 diabetes (T2DM) and those with a higher BMI. In a network meta-analysis, semaglutide was effective but not superior to newer drugs like retatrutide and tirzepatide.
• In combination with metformin, semaglutide significantly improved glycemic control, reducing fasting blood glucose, hemoglobin A1c (HbA1c), and BMI in patients with T2DM. Semaglutide also improved outcomes in heart failure, including body weight reduction and six-minute walk distance.
• Semaglutide reduced albuminuria in diabetic kidney disease patients, though its effects on estimated glomerular filtration rate (eGFR) were variable. Additionally, semaglutide was associated with a 42% reduction in the risk of atrial fibrillation compared to placebo.
• Gastrointestinal Adverse Events: Semaglutide was commonly associated with gastrointestinal side effects, including nausea, vomiting, diarrhea, and constipation. These events were dose-dependent and more frequent compared to placebo, sometimes leading to treatment discontinuation.
• Serious Adverse Events: No significant increase in serious adverse events was reported compared to placebo. However, higher rates of discontinuation due to gastrointestinal disorders were noted in semaglutide-treated patients.
• Specific Concerns: Case reports indicated the occurrence of acute kidney injury (AKI), including acute interstitial nephritis, linked to semaglutide. The incidence of thyroid cancer was less than 1%, suggesting no substantial risk.
• Comparative Safety: Semaglutide had a safety profile similar to other GLP-1 receptor agonists, with a higher incidence of gastrointestinal side effects. Compared to sodium-glucose cotransporter-2 (SGLT2) inhibitors, GLP-1 RAs, including semaglutide, showed higher gastrointestinal event rates but similar overall adverse event rates.
• Diabetes Status and Obesity: Semaglutide showed greater cardiovascular and weight loss benefits in overweight/obese adults without diabetes compared to those with T2DM. Additionally, in T2DM patients, semaglutide significantly improved glycemic control, insulin resistance, and BMI reduction.
• Age, BMI, and Cardiovascular Risk: Patients with higher BMI experienced more substantial weight loss and cardiovascular benefits with semaglutide, while non-diabetic adolescents saw pronounced anti-obesity effects. Semaglutide also improved heart failure outcomes and reduced major cardiovascular events in high-risk patients, regardless of diabetes status.