Generic Liraglutide Approved, Marking First Generic GLP-1 RA Indicated Specifically for Weight Management in the US

Teva Pharmaceuticals has announced the FDA approval and US launch of the first generic version of liraglutide injection (Saxenda), making the glucagon-like peptide-1 receptor agonist (GLP-1) formulation the first in its class specifically indicated for weight loss in the US.

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The FDA originally awarded approval of liraglutide as Saxenda to Novo Nordisk, on December 23, 2014, for chronic weight management in adults with obesity or overweight, in conjunction with a reduced-calorie diet and increased physical activity. In December 2020, the agency expanded the indication to include adolescents (ages 12–17 years) with obesity and a minimum weight of 60 kg. Liraglutide’s approval was based on robust clinical trial data demonstrating its efficacy in both adults and adolescents for long-term weight management.

Clinical Efficacy in Obesity

The GLP-1's clinical benefits for obesity and weight management were established in several large-scale phase III trials. In non-diabetic obese adults, liraglutide (3.0 mg) resulted in an average weight loss of approximately 3.4 kg more than placebo over 56 weeks. Additionally, 25.2% of study participants reached weight loss of more than 10% with liraglutide, compared to 6.7% with placebo. Across premarketing studies, liraglutide also demonstrated improvements other metabolic parameters associated with obesity and overweight, including body mass index (BMI), waist circumference, and blood pressure.

Mechanism of Action

The core therapeutic mechanism of liraglutide is common to the GLP-1 receptor agonist class, ie, GLP-1 receptor-mediated cascades to enhance glucose-dependent insulin secretion, reduce appetite, and delay gastric emptying, and promoting appetite suppression. By mimicking endogenous GLP-1, liraglutide influences both central nervous system appetite pathways and peripheral metabolic processes. Liraglutide, like other GLP-1s, influences reward centers in the brain associated with food motivation and satiety, benefits that may support sustained weight loss.

While GLP-1 receptor activation is central to the effects of all drugs in the class, structural modifications in newer antiobesity medications, such as semaglutide, allow for:

• Greater receptor affinity and potency: Semaglutide, for example, has a higher affinity for the GLP-1 receptor than liraglutide, potentially translating to greater weight loss and glycemic efficacy in head-to-head trials.
• Prolonged dosing intervals: Semaglutide's structure confers resistance to DPP-4 degradation and extends its half-life, making once-weekly dosing possible, compared to liraglutide’s once-daily administration.
• Enhanced clinical outcomes: Recent randomized studies have consistently shown larger reductions in body weight and HbA1c with weekly semaglutide versus daily liraglutide.

The FDA approval may help expand access during current high demand for GLP-1–based antiobesity therapies in the US.