Development of the sodium-glucose co-transporter 2 inhibitor dapagliflozin for the treatment of patients with Type 2 diabetes mellitus

Abstract

Dapagliflozin is a highly selective sodium-glucose co-transporter 2 inhibitor developed for the treatment of Type 2 diabetes mellitus. Its inhibition of sodium-glucose co-transporter 2 blocks glucose reabsorption in the proximal tubule of the kidney, increasing renal glucose excretion via the urine, resulting in reduction of glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose in patients with Type 2 diabetes mellitus. The pharmacokinetics and pharmacodynamics of dapagliflozin are suitable for once-daily dosing. Dapagliflozin improves glycemic control when used as monotherapy and when used in combination with other antidiabetic treatments. Throughout all phases of clinical studies, dapagliflozin was generally well tolerated. Increased events suggestive of urinary tract and genital infections have been reported; most resolved with conventional treatment. Unexpected numerical imbalances between dapagliflozin and comparator were noted for breast and bladder cancers. The potential for increased cancer risk with dapagliflozin needs to be further assessed.

Keywords::

• clinical trial
• dapagliflozin
• diabetes mellitus
• HbA1c
• plasma glucose
• SGLT2

Financial & competing interests disclosure

John E Gerich has consulted for Bristol-Myers Squibb, AstraZeneca, Johnson & Johnson, Boehringer Ingelheim and Merck, and has served on their speakers bureaus. Arnaud Bastien is an employee of Bristol-Myers Squibb. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. Editorial support was provided by Danielle Gross, Tiffany Brake and Janet E Matsuura from Complete Healthcare Communications, Inc. and was funded by Bristol-Myers Squibb and AstraZeneca.