Promising Results Reported for Remogliflozin Etabonate in Mid-Stage Diabetes Trials
SGLT2 inhibitor reduces hemoglobin A1c
Positive results have been reported from two 12-week, phase IIb clinical trials of remogliflozin etabonate (Islet Sciences/BHV Pharma) in patients with type-2 diabetes.
The studies’ primary endpoint was hemoglobin A1c (HbA1c), with secondary endpoints of fasting plasma glucose, serum lipids, body weight, safety, and tolerability.
Data from the two phase IIb trials will be presented at the 74th American Diabetes Association Scientific Sessions, to be held June 13–17 in San Francisco.
Remogliflozin etabonate is a selective SGLT2 inhibitor indicated for type-2 diabetes and nonalcoholic steatohepatitis (NASH).
Both of the phase IIb clinical trials were randomized, double-blind, placebo- and pioglitazone-controlled, parallel-group, dose-ranging studies evaluating the efficacy, safety, and tolerability of multiple doses of remogliflozin etabonate in treatment-naïve subjects with type-2 diabetes. One study dosed remogliflozin etabonate once daily and the other dosed the drug twice daily during the 12-week study period.
At week 12, twice-daily dosing of remogliflozin etabonate produced a statistically significant trend in dose response for the change from baseline (P < 0.001), with changes in HbA1c ranging from –1.0% to –1.4%. Once-daily dosing demonstrated a trend in dose response for the change from baseline in HbA1c above the lowest dose (P < 0.047), with changes in HbA1c ranging from –0.5% to –0.8%.
A statistically significant decrease in body weight (1.36 to 3.51 kg) from baseline was seen in all twice-daily remogliflozin etabonate treatment groups by week 12 compared with the placebo group, and a statistically significant decrease in body weight compared with placebo (1.44 to 1.51 kg) from baseline was seen in all once-daily remogliflozin etabonate groups above the lowest dose.
The primary differentiating factor between dosing regimens was the duration of drug plasma exposure relative to evening postprandial glucose excursions and the subjects’ sleep periods. While twice-daily dosing provided greater relative reductions in HbA1c and body weight, the investigators also observed increases in low-density lipoprotein cholesterol (LDL-C) and in incidence rates of genital fungal infections similar to what has been demonstrated with other SGLT2 inhibitors.
Once-daily dosing of remogliflozin etabonate showed lower reductions in HbA1c and body weight compared with twice-daily dosing but generally resulted in no change in LDL-C and lower incidence rates of genital fungal infections compared with placebo. These results are consistent with the longer plasma exposure from twice-daily dosing having a greater effect on evening postprandial glucose excursions and with shorter plasma exposure from once-daily dosing limiting the undesirable effects of night-time inhibition of SGLT2.
SGLT2 inhibitors block the re-absorption of glucose in the kidney, resulting in reduced blood sugar and HbA1c levels. SGLT2 inhibitors are the only oral anti-diabetic agents that provide significant HbA1c lowering with clinically relevant weight loss through an insulin-independent, beta-cell–sparing mechanism of action.
Source: Islet Sciences; April 16, 2014.