Onglyza (saxagliptin | Bristol-Myers Squibb-Astra Zeneca), a selective reversible inhibitor of dipeptidyl peptidase-4 (DPP-4), has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of type 2 diabetes in adults.
Onglyza received the approval based on the results of eight clinical trials, one of which consisted of 5,000 participants. More than 4,000 participants in this trial received the drug along with recommendations on diet and exercise. The drug was studied as combination therapy with other oral hypoglycemic agents (OHAs); as monotherapy; and in newly diagnosed diabetics who have been prescribed metformin.
The study found statistically significant HbA1C reduction when Onglyza was used along with sulfonylureas, glyburides, thiazalidiones and metformin, and showed a similar effect when administered to newly diagnosed diabetics on metformin as well as in participants on monotherapy. The adverse events were similar to placebo. With the 5 mg dose, the most commonly observed side effects were upper respiratory infection, urinary tract infection and headache. With 2.5 mg dose, headache was reported in ≥5% participants on Onglyza. It was also observed that there was no increase in the risk of cardiovascular events, particularly in those individuals at low risk. The FDA has sought a post-market study to determine the cardiovascular safety in a higher risk population.
DPP-4 inhibitors exert their action by reducing the degradation of a group of gastrointestinal hormones called incretins (glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide), which are responsible for more than 50% of insulin secretion. This results in improved beta-cell function and inhibition of glucagon release from the alpha cells of the pancreas. Other drugs in this group include sitagliptin and vildagliptin.
Although there is an armamentarium of oral hypoglycemics in the market, it has been observed that about half of the adult diabetics are unable to maintain their blood glucose levels in the optimal range. The DPP-4 inhibitors have been developed in the hope to address the immense need for a drug which can effectively lower blood glucose and prevent serious consequences of poorly-controlled type 2 diabetes.
Apart from the favorable side effect profile, Onglyza also carries the advantages of being able to reduce both fasting and postprandial blood glucose levels, a pharmacokinetic profile which allows once daily dosing (2.5 or 5 mg) irrespective of meals, and a neutral effect on body weight. The drug can be used safely in patients with hepatic and renal impairment, without requiring dose adjustments based on age and gender. However, Onglyza should not be used to treat type 1 diabetes or diabetic ketoacidosis.
About Bristol-Myers Squibb Co.: Headquartered in New York, the biopharmaceutical company achieved net sales of $20.6 billion in 2008. Their top 3 selling products include PLAVIX ® (clopidogrel bisulfate), ABILIFY ® (aripiprazole), and AVAPRO ®/AVALIDE ® (irbesartan and irbesartan-hydrochlorothiazide, respectively).
About Astra Zeneca: A leading pharmaceutical company formed by the re-merger of Swedish Astra AB and British Zeneca Group PLC in 1999. The company develops, manufactures and sells drugs related to gastrointestinal, vascular, neuropsychiatric, cardiac, respiratory, infectious and oncological disorders.
References
1. FDA Approves New Drug Treatment for Type 2 Diabetes. Press Release. FDA. Last accessed August 03, 2009.
2. U.S. Food and Drug Administration Approves ONGLYZAâ„¢ (saxagliptin) for the Treatment of Type 2 Diabetes Mellitus in Adults. Press Release. Bristol-Myers Squibb. Last accessed August 03, 2009.
3. Deacon CF, Holst JJ. Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. Adv Ther. 2009 May;26(5):488-99.
