Thursday , October 19 2017
Home / Resources / Articles / LX4211 Improved Glucose Control without Dose-Increasing Glucosuria in Type 2 Diabetes

LX4211 Improved Glucose Control without Dose-Increasing Glucosuria in Type 2 Diabetes

In patients with type 2 diabetes, LX4211 produced greater dose-ranging effects on HbA1c than on glucosuria…. 

LX4211 is a dual inhibitor of sodium glucose cotransporters 1 and 2 (SGLT1 and SGLT2). A 12-week dose-ranging study was conducted in order to evaluate the efficacy and safety of LX4211 in type 2 diabetes.

Researchers randomly assigned 299 patients with similar baseline characteristics that were inadequately controlled on metformin to 75 mg once a day, 200 mg once daily, 200 mg twice daily, or 400 mg once daily of LX4211 or placebo. These patients had an average age of 55.9 years, an HbA1c of 8.1% (65 mmol/mol), a BMI of 33.1 kg/m2, and a BP of 124/79 mmHg. The change in HbA1c from baseline to week 12 was the primary end point, and the changes in blood pressure (BP) and body weight were the secondary end points.

Throughout the 12 weeks, HbA1c was significantly reduced in a dose-dependent manner by 0.42% (4.6 mmol/mol) with 75 mg once a day LX4211, 0.52% (5.7 mmol/mol) with 200 mg once daily LX4211, 0.80% (8.7 mmol/mol) with 200 mg twice daily LX4211, and 0.92% (10.0 mmol/mol) with 400 mg once daily LX4211 (p <0.001 each), while placebo only caused a 0.09% (1.0 mmol/mol) reduction. The 400 mg once daily LX4211 produced greater HbA1c reductions than 200 mg once daily LX4211 without higher urinary glucose excretion, and researchers believe this is due to SGLT1 inhibition. Although diastolic BP was unchanged (−1.6 mmHg; p=0.164), body weight decreased by 1.85 kg (p <0.001) and systolic BP was decreased by 5.7 mmHg (p <0.001) in the LX4211 groups. LX4211 caused mild to moderate adverse events similar to placebo. These included urinary tract infections and gastrointestinal-related events, but genital infections only occurred in the LX4211 groups (0–5.0%). Hypoglycemia did not occur in the any of the groups.

LX4211 produced significantly greater dose-ranging effects on HbA1c levels than on glucosuria in patients with type 2 diabetes that were on metformin. There were significant reductions in body weight and systolic BP that were also associated with LX4211.

Practice Pearls:

  • Patients taking LX4211 experienced significant dose-dependent reductions in HbA1c without dose-increasing glucosuria.
  • LX4211 also produced significant reductions in body weight and systolic BP.
  • Mild to moderate adverse events, such as urinary tract infections and gastrointestinal-related events, occurred similarly among all patient groups, and hypoglycemia did not occur in any of the groups; however, only the LX4211 groups experienced genital infections.

Published online on Sept 11, 2014 in Diabetes Care.