Novo Nordisk reported the successful completion of their “SUSTAIN1” phase IIIa trial of Semaglutide. Semaglutide is Novo Nordisk’s novel glucagon-like peptide-1 (or GLP-1) analogue that has been developed for the treatment of those suffering with type 2 Diabetes mellitus.
GLP-1 forms naturally in the body and is derived from the same precursor protein as glucagon, which is the hormone that acts as the physiological antagonist of insulin. GLP-1 is secreted by intestinal L-cells in response to the ingestion of nutrients and binds to the GLP-1 receptor, found prominently on islet cells of the pancreas. This triggers an increase in insulin secretion with a concurrent inhibition in the release of glucagon, thus acting to lower blood glucose levels by insulin-dependant uptake of the sugar by the body’s cells via glucose transporters. The presence of GLP-1 receptors within other tissues outside of the endocrine system – such as enteric neurons and cells in the central nervous system – allows for additional physiologic effects including the suppression of hunger and the breakdown of fat stores; These being potentially useful attributes in the treatment of Type 2 Diabetes that sparked a number of foundational studies of GLP-1 agonists in the mid-1990’s.
GLP-1 agonists have been licensed for use in type 2 diabetics since 2005, when Astrazeneca’s Exenatide first hit the market in the form of an ante cibum subcutaneous injection. The novel agonist Semaglutide, however, has been designed for use as a once-weekly injection.
Novo Nordisk’s SUSTAIN1 is the first of six Semaglutide trials that will be releasing their results throughout the next nine months. SUSTAIN1 was able to achieve their primary goal of significant reductions in glycated haemoglobin (HbA1c), from a mean baseline of 8.5% to around 1.5%, using 0.5mg and 1.0mg doses of Semaglutide versus a placebo. This was performed in a cohort of 388 previously unmedicated type 2 diabetics, with once-weekly injections over a 30-week period to assess the efficacy and safety of the treatment.
Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk said about the news:
“We are excited about these results, which confirm that semaglutide has the potential to help people with type 2 diabetes achieve both good glycaemic control and a significant weight loss with one weekly injection”.
Following on from the success of SUSTAIN1, SUSTAIN2 will assess the safety of the drug versus sitagliptin as an adjuvant therapy with metformin over a 56-week period in 811 type 2 diabetics. The culmination of the six SUSTAIN trials will assess the safety and efficacy of Semaglutide in over 7000 people with type 2 diabetes including those already receiving treatment and those with common diabetic co-morbidities.
With only 5 other licensed GLP-1 agonists approved for use, including Novo Nordisk’s other GLP-1 analogue Liraglutide, the approval of Semaglutide could have a big impact on the availability of GLP-1 drugs for patients and for competition in this relatively niche marketplace.