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document
Study design and rationale of a dose-ranging trial of LX4211 , a dual inhibitor of SGLT1 and SGLT2 , in type 2 diabetes inadequately controlled on metformin monotherapy . Sodium-glucose cotransporters 1 ( SGLT1 ) and 2 ( SGLT2 ) are the major cellular transporters responsible for gastrointestinal ( GI ) glucose absorption and renal glucose reabsorption , respectively . LX4211 , a dual inhibitor of SGLT1 and SGLT2 , reduces glucose absorption from the GI tract and enhances urinary glucose excretion . Although several SGLT2-selective inhibitors have been tested in large phase 2 studies , dual inhibition of SGLT1 and SGLT2 is novel at this stage of drug development , and it has implications for clinical-trial design . In this article , we describe the design and rationale of a phase 2 , multicenter , randomized , double-blind , placebo-controlled , parallel group study to evaluate the safety and efficacy of LX4211 in subjects with type 2 diabetes mellitus who have inadequate glycemic control on metformin monotherapy . The primary endpoint is the change in glycated hemoglobin A1c from baseline to week 12 . Secondary endpoints include the proportion of subjects achieving a glycated hemoglobin A1c value of < 7 % , change from baseline in fasting plasma glucose and postprandial glucose ( as part of an oral glucose tolerance test ) , body weight , and blood pressure . Safety is evaluated with particular focus on hypoglycemia , GI symptoms , and incidence of genitourinary tract infections .
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Intervention_Pharmacological
LX4211
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Intervention_Pharmacological
LX4211
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
LX4211
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Outcome_Other
safety and efficacy
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Outcome_Physical
glycemic control
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Outcome_Physical
glycated hemoglobin A1c
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Outcome_Physical
proportion of subjects achieving a glycated hemoglobin A1c value of < 7 % , change from baseline in fasting plasma glucose and postprandial glucose ( as part of an oral glucose tolerance test ) , body weight , and blood pressure .
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Outcome_Other
Safety
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Outcome_Physical
hypoglycemia , GI symptoms , and incidence of genitourinary tract infections