Can the 15-Kilogram Weight Loss Breakthrough Be Replicated? Oral Semaglutide Obesity Trial Set to Launch

On April 21, 2021, Novo Nordisk announced that it would initiate a pivotal Phase 3a clinical trial to evaluate the efficacy and safety of oral semaglutide in approximately 1,000 patients with obesity or overweight and comorbidities. This 68-week global trial is scheduled to commence in the second half of this year. Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist; its injectable formulation achieved an average weight loss of 15 kg in patients with obesity in the STEP clinical trial program.

1. Health Risks of Obesity

Obesity is a chronic disease requiring long-term management and is associated with numerous serious complications and reduced life expectancy. Complications related to obesity include type 2 diabetes, heart disease, obstructive sleep apnea, non-alcoholic fatty liver disease, and certain cancers. Obesity also increases the risk of severe illness and hospitalization due to COVID-19. As living standards improve, its prevalence continues to rise. Obesity is a global crisis that is also severely affecting China. It is estimated that approximately 650 million adults worldwide are living with obesity.

2. What is Semaglutide

Semaglutide is a long-acting GLP-1 analog. GLP-1 is a peptide hormone secreted by intestinal cells that promotes insulin secretion and inhibits glucagon secretion through a glucose concentration-dependent mechanism by binding to GLP-1 receptors, thereby facilitating glucose metabolism. Semaglutide significantly improves glycemic control in patients with type 2 diabetes, accompanied by a lower risk of hypoglycemia. Additionally, it delays gastric emptying and suppresses appetite, inducing weight loss by reducing appetite and decreasing food intake. The U.S. FDA has approved Ozempic, in conjunction with diet and exercise, to improve glycemic control in adults with type 2 diabetes. Furthermore, it significantly reduces the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes.

3. Ozempic and the STEP Trials

The injectable semaglutide is marketed under the brand name Ozempic. In the STEP clinical trial program evaluating once-weekly subcutaneous semaglutide (2.4 mg) for chronic weight management, patients receiving semaglutide injections reported a 16–18% reduction in body weight compared with placebo among more than 4,500 enrolled adults with obesity or overweight.

4. Rybelsus and the PIONEER Trials

Rybelsus is the brand name for oral semaglutide. It is the first oral GLP-1 receptor agonist (GLP-1 RA) approved by the FDA. Its introduction has transformed the treatment landscape for patients with type 2 diabetes, who previously required daily or weekly injections of GLP-1 RAs, by providing a less invasive and more convenient option for glycemic control. In the United States, the European Union, and Japan, oral Rybelsus at doses of 7 mg or 14 mg is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. The approval of Rybelsus was based on results from 10 PIONEER clinical trials, which enrolled a total of 9,543 patients with type 2 diabetes. Compared with controls, oral semaglutide reduced both glycated hemoglobin (HbA1c) levels and body weight. In clinical trials, Rybelsus demonstrated a favorable safety profile and good tolerability, with the most common adverse reaction being mild to moderate nausea over time.

References:

[1] Novo Nordisk to initiate phase 3a development in obesity with oral semaglutide Retrieved April 21, 2021, from https://www.globenewswire.com/news-release/2021/04/21/2214286/0/en/Novo-Nordisk-to-initiate-phase-3a-development-in-obesity-with-oral-semaglutide.html

Note: This article aims to introduce advances in pharmaceutical and health research and does not constitute treatment recommendations. For guidance on treatment plans, please consult a qualified medical institution.

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