Content area
Full Text
Published online: 22 May 2014
© Springer International Publishing Switzerland 2014
Abstract Luseogliflozin [Lusefi® (Japan)] is an orally active second-generation sodium-glucose co-transporter 2 (SGLT2) inhibitor developed by Taisho Pharmaceutical for the treatment of patients with type 2 diabetes mellitus (T2DM). The drug has received its first global approval for this indication in Japan, either as monotherapy or in combination with other antihyperglycaemic agents. This article summarises the milestones in the development of luseogliflozin leading to this first approval for the treatment of T2DM.
1 Introduction
Inhibition of renal glucose reabsorption is emerging as a novel therapy for patients with type 2 diabetes mellitus (T2DM). In particular, blocking the sodium-glucose cotransporter 2 (SGLT2)-a low-affinity high-capacity transporter localised to the renal proximal tubules-has been shown to suppress glucose reabsorption, leading to increased urinary excretion with a concomitant reduction in plasma glucose levels. Compounds selective for SGLT2 are desirable as SGLT1 is highly expressed in the gastrointestinal tract but only moderately expressed in the kidneys [1, 2].
Luseogliflozin [Lusefi^ (Japan)] is a selective SGLT2 inhibitor, which received its first marketing approval for the treatment of T2DM on the 24th of March 2014. The drug has received approval as 2.5 and 5 mg oral tablets with a recommended starting dose of 2.5 mg once daily. This may be increased to 5 mg once daily if necessary for optimal clinical effect [3, 4].
The approval of luseogliflozin was based on a series of phase III trials in patients with T2DM; all were conducted in Japan in patients of Japanese ethnicity. Two trials evaluated the efficacy of luseogliflozin in combination with other antihyperglycaemic agents in patients with suboptimal glycaemic control on that agent alone, and two trials evaluated luseogliflozin as monotherapy.
1.1 Company Agreements
In November 2012, Novartis licensed the marketing rights for luseogliflozin in Japan. Under the terms of this agreement, luseogliflozin will be manufactured by Taisho Pharmaceutical and co-marketed by both Taisho and Novartis in Japan. Taisho will receive an upfront payment and milestone payments from Novartis [5].
2 Scientific Summary
2.1 Pharmacodynamics
Luseogliflozin is a potent inhibitor of SGLT2 (IC50 2.26 nM) with a 1,650-fold greater selectivity for SGLT2 over SGLT1 [6]. The drug competitively inhibited sodiumdependent 14C-a-methylglucoside uptake (Ki value 1.10 nM) in Chinese hamster ovary-K1...