LX4211, a Dual SGLT1/SGLT2 Inhibitor, Improved Glycemic Control in Patients With Type 2 Diabetes in a Randomized, Placebo-Controlled Trial

被引：198

作者：

Zambrowicz, B. ^{[1
]}

Freiman, J. ^{[1
]}

Brown, P. M. ^{[1
]}

Frazier, K. S. ^{[1
]}

Turnage, A. ^{[1
]}

Bronner, J. ^{[1
]}

Ruff, D. ^{[2
]}

Shadoan, M. ^{[1
]}

Banks, P. ^{[1
]}

Mseeh, F. ^{[1
]}

Rawlins, D. B. ^{[3
]}

Goodwin, N. C. ^{[3
]}

Mabon, R. ^{[3
]}

Harrison, B. A. ^{[3
]}

Wilson, A. ^{[1
]}

Sands, A. ^{[1
]}

Powell, D. R. ^{[1
]}

机构：

[1] Lexicon Pharmaceut Inc, The Woodlands, TX USA

[2] Icon Dev Solut, San Antonio, TX USA

[3] Lexicon Pharmaceut Inc, Princeton, NJ USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2012年 / 92卷 / 02期

关键词：

GLUCAGON-LIKE PEPTIDE-1; SELECTIVE SGLT2 INHIBITOR; BETA-CELL FUNCTION; GLUCOSE-HOMEOSTASIS; ANTIDIABETIC DRUG; INSULIN; DAPAGLIFLOZIN; PHLORHIZIN; ASSOCIATION; PHLORETIN;

D O I：

10.1038/clpt.2012.58

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Thirty-six patients with type 2 diabetes mellitus (T2DM) were randomized 1:1:1 to receive a once-daily oral dose of placebo or 150 or 300 mg of the dual SGLT1/SGLT2 inhibitor LX4211 for 28 days. Relative to placebo, LX4211 enhanced urinary glucose excretion by inhibiting SGLT2-mediated renal glucose reabsorption; markedly and significantly improved multiple measures of glycemic control, including fasting plasma glucose, oral glucose tolerance, and HbA(1c); and significantly lowered serum triglycerides. LX4211 also mediated trends for lower weight, lower blood pressure, and higher glucagon-like peptide-1 levels. In a follow-up single-dose study in 12 patients with T2DM, LX4211 (300 mg) significantly increased glucagon-like peptide-1 and peptide YY levels relative to pretreatment values, probably by delaying SGLT1-mediated intestinal glucose absorption. In both studies, LX4211 was well tolerated without evidence of increased gastrointestinal side effects. These data support further study of LX4211-mediated dual SGLT1/SGLT2 inhibition as a novel mechanism of action in the treatment of T2DM.

引用

页码：158 / 169

页数：12

共 58 条

[21] Remogliflozin etabonate, in a novel category of selective low-affinity sodium glucose cotransporter (SGLT2) inhibitors, exhibits antidiabetic efficacy in rodent models [J].