Research presented in June at the American Diabetes Association (ADA) meeting highlighted potential advances for diabetes patients who use drugs in a class called incretin mimetics –specifically GLP-1 (glucagon-like peptide 1) agonists — to help control their blood sugar. Such drugs work by increasing the secretion of insulin from the pancreas, inhibiting glucagon (a hormone that raises blood sugar levels) release, and slowing the absorption of glucose from the gut. These activities work together to lower blood sugar levels. Incretin-mimetics also reduce appetite, providing a second health benefit of weight loss. Moreover, research has suggested that some GLP-1 agonists can also reduce cardiovascular risks in diabetes patients. There are a number of currently marketed GLP-1 drugs; to date, however, all have been injectable therapies.
Novo Nordisk is seeking to transform the market for GLP-1 drugs with a pill, which some analysts say could eventually sell more than $5 billion per year. Novo already has two injectable GLP-1 agonists on the market — top-selling Victoza, a once-daily formulation of liraglutide, and Ozempic, a once-weekly formulation of semaglutide. The company is now aiming for the approval and market positioning of an oral semaglutide. Novo Nordisk has been conducting 10 Phase 3 studies in more than 9,000 patients. Four of the studies are now complete, and in June they announced data from two of them.
The PIONEER 4 study showed the oral drug’s non-inferiority to Victoza in controlling blood sugar levels in patients with type 2 diabetes who were inadequately controlled by metformin. The PIONEER 7 study showed Novo’s oral drug to be superior to Merck’s Januvia (oral sitagliptin) in lowering HbA1c—a key measure of blood sugar levels — and promoting weight loss. Novo seeks to offer the injectable Ozempic as a once-weekly GLP-1 alternative, while positioning the oral drug, also taken daily, as a more convenient alternative to once-daily therapies. Potential limitations to the oral drug’s market acceptance exist, however: patients cannot eat for at least 30 minutes after taking it, which could compromise adherence to therapy. Additionally, the GLP-1 drug class as a whole has been associated with side effects of nausea and vomiting in some patients.
Recent research suggests that GLP-1 therapies may also provide benefits to adults with type 1 diabetes. In a one-year, randomized, placebo-controlled study in 46 patients with Type 1 diabetes, daily Victoza injections significantly improved blood glucose control and increased weight loss. As many type 1 diabetes patients struggle to control blood glucose levels, this added therapy could help prevent complications and make patients’ lives more stable and predictable.
Eli Lilly and AstraZeneca are also looking to challenge the GLP-1 market. Lilly is developing an oral GLP-1, but its candidate is still in preclinical testing. AstraZeneca is developing a potential first-in-class drug, MEDI0382. This injectable peptide activates both the GLP-1 and the glucagon receptors, mimicking the effects of oxyntomodulin, a hormone released after eating. Results of a Phase 2a study in type 2 diabetes showed that treatment with MEDI0382 significantly reduced both fasting and post-meal glucose levels compared to placebo. Moreover, the drug produced significantly greater weight loss compared to placebo, and reduced liver fat in treated patients, suggesting that MEDI0382 could potentially also be a candidate to treat NASH, or “fatty liver disease.”