Novo begins the STEP trial program in obesity

Novo Nordisk launched the STEP phase 3 clinical trial program for semaglutide 2.4 mg in obesity in June 2018, after doctors noticed that people taking semaglutide for type 2 diabetes, sold as Ozempic, were losing substantial weight beyond what the diabetes indication called for ^[1][2]. That observation pushed the company to test a higher dose of the same drug specifically for chronic weight management, a program that would later be known as STEP ^[2].

The STEP program formed the clinical basis for Wegovy, the version of semaglutide the FDA approved for weight loss. According to the drug's approval history, a 68-week trial reported in March 2021 showed that adults with obesity treated with semaglutide 2.4 mg achieved and maintained a significant amount of weight loss ^[2]. The FDA approved Wegovy injection for adults with obesity on June 4, 2021 ^[2]. Semaglutide itself, the active ingredient in Ozempic, Rybelsus, and Wegovy, is a GLP-1 receptor agonist that works partly by activating GLP-1 receptors in brain regions that regulate appetite, which lowers caloric intake ^[2].

Wegovy's approved uses have expanded well beyond the original 2021 obesity clearance. The FDA later approved Wegovy for teens aged 12 and older in December 2022, for cardiovascular risk reduction in adults with obesity or overweight and established cardiovascular disease in March 2024, and, in August 2025, for treatment of metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis under an accelerated approval pathway ^[2]. In the SELECT cardiovascular outcomes trial, semaglutide 2.4 mg reduced the risk of major adverse cardiovascular events by 20% in adults with overweight or obesity, according to results reported in August 2023 ^[2].

Why it matters for patients

The STEP program's 2018 start explains why Wegovy exists as a separate, higher-dose product from Ozempic even though both contain the same molecule, semaglutide ^[1][2]. Patients considering either drug should understand that Wegovy's approved uses now go beyond weight loss alone, including cardiovascular risk reduction and MASH, each with its own trial evidence and approval date ^[2]. The product label for Wegovy carries a boxed warning about thyroid C-cell tumor risk, and common side effects reported in trials include nausea, diarrhea, vomiting, constipation, and other gastrointestinal symptoms ^[2]. Because Wegovy is approved for multiple conditions through separate trials and applications, the specific evidence behind each use differs, and patients may want to know which indication applies to their own situation.

What happens next

The sources describe ongoing research into semaglutide's effects. As of documented reporting through 2026, Novo Nordisk has continued testing higher-dose and oral formulations of Wegovy, including a Wegovy pill that received FDA approval in December 2025 as the first oral GLP-1 for weight loss in adults ^[2]. A higher-dose Wegovy HD injection received FDA approval in March 2026 ^[2]. The company has also reported new trial data on outcomes such as heart attack and stroke risk, liver health in MASH patients, and weight loss in specific patient subgroups, with several analyses presented at scientific meetings through 2026 ^[2]. The sources do not specify what additional STEP trial results, if any, remain unpublished or under review.