Impact case study database

Bailey was previously instrumental in the development of metformin as the most-prescribed drug worldwide for type 2 diabetes, both in terms of fundamental research and design/implementation of clinical trials ( S5.1) and as a consequence, was selected by BMS as PI for the initial phase III clinical trials of dapagliflozin ( S5.2). The resulting clinical research provided the primary evidence required to illustrate the efficacy and safety profile of dapagliflozin as a suitable medicine for the treatment of type 2 diabetes, both as a monotherapy ( S3.5) and as a combination therapy with metformin ( S3.2). From those and subsequent phase III clinical trials, this clinical research into dapagliflozin has resulted in:

• Following formal launch of the drug in the EU in 2012 as both a mono- and combined therapy, dapagliflozin has since been approved for routine clinical use in Europe, North America and most other regions of the world ( S5.3). The National Institute for Health and Care Excellence (NICE), which assessed the clinical studies described above, concluded that the improved management of type 2 diabetes afforded by dapagliflozin (and its related compounds) will enhance patient quality of life, reduce complications and hospital admissions, and provide substantial cost-benefits to the NHS and other healthcare systems ( S5.4). Consequently, dapagliflozin is now the most commonly-used agent in the class of SGLT-2 inhibitors, with more than with more than $1.54 billion sales in 2019, a rise of 11% from 2018 ( S5.5).

Owing to the unusual mechanism of action of dapagliflozin (it affects glucose excretion rather than glucose homeostasis via insulin-based control), dapagliflozin may be combined successfully with other drugs including metformin and insulins ( S5.3). For those for whom monotherapy gives inadequate control, combination therapy with an SGLT-2 inhibitor such a dapagliflozin can prove effective and so delay the use of injectable therapies such as insulins. Conversely, those already on insulin are generally required to reduce their dose when used in combination with dapaglifozin ( S5.7).

Unlike several other treatments for type 2 diabetes such as sulphonylureas and insulins, dapagliflozin assists control of body weight and blood pressure, and has recently received approval for use as an adjunct to insulin in the treatment of type 1 diabetes ( S5.7). Dapagliflozin has also been shown to reduce rates of cardiovascular death and hospitalization for heart failure, and is now approved by FDA to assist treatment of type 2 diabetes patients with cardiovascular conditions ( S5.8).

Additionally, dapagliflozin has been shown to protect against deteriorating renal function, promote secretion of beneficial adipocyte hormones (adiponectin and leptin), and increase uric acid excretion, raising the possibility of therapeutic uses to treat hyperuricaemia ( S5.9, S3.5). Accordingly, dapagliflozin has recently been granted Breakthrough Therapy Designation in the US for patients with chronic kidney disease, with and without type-2 diabetes. Finally, it is noted that the successful early clinical studies with dapagliflozin encouraged development of related compounds including canagliflozin and empagliflozin.

BMS and AZ entered into a “ Diabetes alliance” in 2007 ( S5.3) in which BMS developed dapagliflozin. In February 2014, AZ subsequently completed “acquisition of the entirety of Bristol-Myers Squibb’s interests in the companies’ diabetes alliance ”, for a total of $2.7 billion, of which $0.6 billion related to royalty payments up to 2025 for Farxiga (dapagliflozin) in the USA ( S5.10).