Novo Nordisk Announces Superior HbA1c Reduction with Once-Weekly Semaglutide 2.0 mg in Type 2 Diabetes Patients in SUSTAIN FORTE Trial

Compiled by Keke

On November 17, Novo Nordisk announced the primary results of the SUSTAIN FORTE trial, a 40-week Phase 3b clinical study conducted in 961 patients with type 2 diabetes requiring intensified treatment. The trial aimed to evaluate the efficacy and safety of once-weekly semaglutide at doses of 2.0 mg and 1.0 mg as add-on therapy to metformin and/or sulfonylureas. The results demonstrated that at week 40, semaglutide 2.0 mg significantly reduced glycated hemoglobin (HbA1c) compared with semaglutide 1.0 mg administered once weekly, thereby meeting the trial’s primary endpoint.

In assessing the expected therapeutic efficacy (assuming all patients adhered to treatment and did not initiate other therapies for type 2 diabetes), it was found that from a higher mean baseline HbA1c of 8.9%, patients treated with 2.0 mg semaglutide achieved a reduction in HbA1c of 2.2%, compared to a reduction of 1.9% with 1.0 mg semaglutide, which was statistically significant. The American Diabetes Association (ADA) sets the treatment target at an HbA1c level below 7.0%; this target was achieved by 68% of patients in the 2.0 mg semaglutide group, compared to 58% in the 1.0 mg group. Furthermore, from a mean baseline body weight of 99.3 kg, patients in the 2.0 mg semaglutide group experienced a weight loss of 6.9 kg, compared to 6.0 kg in the 1.0 mg group, which was also statistically significant.

In the treatment policy estimand analysis (i.e., treatment effect regardless of adherence to treatment or initiation of other type 2 diabetes therapies), patients receiving 2.0 mg semaglutide exhibited a 2.1% reduction in HbA1c, compared with a 1.9% reduction in those receiving 1.0 mg. Furthermore, patients in the 2.0 mg group experienced a weight loss of 6.4 kg, compared with 5.6 kg in the 1.0 mg group; however, this difference was not statistically significant.

Trial data also demonstrated that both doses of semaglutide were safe and well tolerated. The most common adverse reactions were gastrointestinal disorders, which were predominantly mild to moderate in severity, decreased gradually over time, and were consistent with those observed with GLP-1 receptor agonists. Compared with the 1.0 mg dose, the 2.0 mg dose of semaglutide had a similar profile of gastrointestinal adverse reactions, with nausea rates of approximately 15% for both doses. The rates of treatment discontinuation due to adverse events were similar for both doses, at less than 5%.

It is reported that the SUSTAIN trial program is a continuous clinical development plan for the weekly subcutaneous injection of semaglutide solution, comprising 11 Phase 3 global clinical trials, including trials focused on cardiovascular outcomes, and enrolling more than 11,000 adults with type 2 diabetes. The 1.0 mg injectable formulation of semaglutide (brand name Ozempic) was approved in the United States in 2017 for the treatment of type 2 diabetes, followed by the approval of its oral formulation (brand name Rybelsus) in 2019, making it the first glucagon-like peptide-1 (GLP-1) receptor agonist therapy approved in the United States that does not require injection.

Reference source: Once-weekly semaglutide 2.0 mg demonstrates superior reduction in HbA1c vs once-weekly semaglutide 1.0 mg in people with type 2 diabetes in the SUSTAIN FORTE trial