Among the piles of data pouring out of the American Diabetes Association meeting in Philadelphia, AstraZeneca/Bristol-Myers Squibb, Johnson & Johnson and Eli Lilly/Boehringer Ingelheim have been extolling the virtues of their respective SGLT2 inhibitors.
First up, AstraZeneca and B-MS announced results from a Phase III study that showed dapagliflozin 10mg demonstrated significant reductions in blood sugar levels compared with placebo at 24 weeks when either agent was added to treatment with Merck & Co's dipeptidyl peptidase IV (DPP-4) inhibitor Januvia (sitagliptin), with or without metformin, in adults with type 2 diabetes. The results were maintained over a 24-week extension.
The study also demonstrated significant reductions in total body weight and fasting plasma glucose levels in patients taking dapagliflozin added to sitagliptin, with results maintained throughout the duration of the study extension. AstraZeneca and B-MS noted that patients were questioned at each study visit for signs, symptoms or events suggestive of genital and urinary tract infections and these events were more frequent with the dapagliflozin treatment group.
Last month, the Committee for Medicinal Products for Human Use of the European Medicines Agency issued a positive opinion recommending the approval of dapagliflozin, which will be called Forxiga. However, earlier this year, the US Food and Drug Administration issued a complete response letter for the drug and requested additional data from ongoing studies amid concerns of possible liver damage and a potential link with breast and bladder cancer.
If approved, dapagliflozin would be the first in the new sodium-glucose cotransporter 2 (SGLT2) class of drugs, which works independently of insulin. By inhibiting SGLT2, these drugs cause a substantial increase in the amount of glucose that flows out in the urine, hence the aforementioned infections. However, a potential advantage of this class is that the mechanism of action is independent of insulin, making it potentially easier to combine SGLT2 inhibitors with other drugs.
Back to the ADA meeting and J&J presented results from five Phase III studies evaluating its SGLT2 inhibitor canagliflozin in monotherapy and in add-on combination use. They showed that the drug provided substantial and sustained glycaemic improvements in adults with type 2 diabetes, and was generally well tolerated.
In two of these studies comparing canagliflozin to current standard treatments - Januvia and Sanofi's Amaryl (glimepiride) - the J&J drug, dosed once-daily at 300mg, provided significantly greater reductions in A1C levels relative to both comparators with similar overall incidence of adverse events.
The canagliflozin clinical programme has enrolled more than 10,300 patients in nine studies, and a fortnight ago, the drug was filed with the US Food and Drug Administration.
Finally, Boehringer and Lilly presented Phase IIb results that showed empagliflozin, alone or as an add-on to metformin, reduced haemoglobin A1c levels, fasting plasma glucose levels and body weight when given to adults with type 2 diabetes for up to 90 weeks. The firms' SGLT2 inhibitor is currently in Phase III with over 14,500 patients planned to be enrolled.