Clinical trials in 2024 are highlighting the expanded benefits of glucagon-like peptide 1 (GLP-1)-based medicines, extending their utility beyond glucose control and weight loss to address a variety of disorders, including cardiovascular and renal diseases, sleep apnea, and metabolic liver disease.
Expanding Applications of GLP-1 Agonists
GLP-1-based therapies have transformed the management of type 2 diabetes mellitus. These agents mimic the incretin hormone GLP-1, enhancing glucose-dependent insulin secretion, delaying gastric emptying, and managing appetite. The resulting health benefits include improved glycemic control and significant weight loss, a critical factor in addressing obesity-associated comorbidities.
Semaglutide, a GLP-1 agonist, has been extensively studied for its versatility, efficacy, and ability to address multiple metabolic and cardiovascular concerns simultaneously. This growing body of evidence signifies a shift in the perception of GLP-1 therapies, from antidiabetic agents to comprehensive tools for improving metabolic health. The clinical benefits of GLP-1-based therapies include glucose control, improvements in cardiovascular health and renal outcomes, and benefits in conditions such as obstructive sleep apnea.
Cardiovascular Benefits Demonstrated in SELECT Trial
The Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) trial investigated the cardiovascular benefits of semaglutide in individuals with obesity but without diabetes. The trial reported a 20% reduction in major cardiovascular events, including myocardial infarction, stroke, and cardiovascular death.
These results were consistent across various demographic and clinical subgroups, including those with differing body mass indices (BMIs), ages, and comorbidities. Notably, the benefits were evident within months, significantly faster than in earlier trials involving diabetes patients.
Renal Function Support in FLOW Trial
The Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial reported the efficacy of semaglutide in protecting renal function among type 2 diabetes patients with chronic kidney disease. A 24% reduction in kidney-related events was observed, along with significant reductions in body weight and hemoglobin A1c (HbA1c) levels. These findings are particularly significant given the growing prevalence of diabetes-associated kidney complications.
Potential in Treating Obstructive Sleep Apnea
GLP-1 therapies have also shown promise in treating obstructive sleep apnea, a condition often linked to obesity. Tirzepatide, a dual GLP-1 and gastric inhibitory polypeptide receptor agonist, has been shown to significantly reduce apnea episodes and promote weight loss in clinical trials. These outcomes suggest a novel therapeutic approach for managing sleep apnea through metabolic interventions, further broadening the utility of GLP-1-based therapies.
Addressing Metabolic Liver Disease
GLP-1-based therapies have demonstrated remarkable potential in addressing metabolic liver diseases, such as metabolic dysfunction-associated steatohepatitis (MASH). MASH is a chronic liver condition characterized by fat accumulation and inflammation that often progresses to fibrosis or cirrhosis if untreated. The emergence of GLP-1 receptor agonists and dual agonists, such as survodutide, offers a promising approach to managing MASH.
Recent phase II trials have demonstrated the efficacy of survodutide in improving liver health in individuals with biopsy-confirmed MASH. Weekly doses of survodutide have been shown to significantly reduce MASH symptoms, with up to 67% of survodutide recipients experiencing a 30% or greater reduction. Moreover, weight loss of 10-13% was observed in treated individuals, underscoring the role of weight reduction in alleviating liver inflammation and fibrosis.
These benefits were observed without worsening fibrosis in most cases, marking a critical advancement in the treatment of liver diseases associated with obesity and metabolic dysfunction. The mechanisms involved in these health benefits appear to extend beyond those attributed to weight loss, with GLP-1 agonists exerting anti-inflammatory effects, potentially mediated by their actions on non-hepatocyte cells within the liver. This anti-inflammatory activity is a promising area of exploration, suggesting additional therapeutic pathways independent of weight management.
GLP-1 agonists have been well-tolerated in trials, with adverse effects primarily limited to mild gastrointestinal symptoms, thus enhancing their suitability for long-term use.
