The investigational SGLT2 inhibitor remogliflozin showed benefits for glucose lowering in type 2 diabetes…
The investigational SGLT2 inhibitor remogliflozin etabonate showed significant benefits for glucose control among patients with type 2 diabetes, a randomized study found.
The difference from placebo in hemoglobin HbA1c at 12 weeks with 250 mg per day of remogliflozin was -0.56% (95% CI minus 0.95 to-minus 0.16, P=0.006), according to William O. Wilkison, PhD, of Islet Sciences in Raleigh, N.C., and colleagues.
In contrast, treatment with pioglitazone, 30 mg once daily, had a difference from placebo of minus 0.19% (95% CI minus 0.58-0.20, P=0.337), the researchers reported online in Diabetes, Obesity, and Metabolism.
"Inhibition of sodium-dependent glucose transporter 2 (SGLT2) offers a new approach for the treatment of type 2 diabetes through increased renal glucose excretion, which results in decreased blood glucose and weight loss," Wilkison and colleagues wrote.
To examine the effects of remogliflozin, "a potent and selective O-glycoside inhibitor of SGLT2" given as monotherapy in treatment-naive patients with diabetes, the researchers enrolled 241 participants whose mean age was 53 and whose mean duration of diabetes was 2.5 years.
Mean body mass index was 32 kg/m2, and baseline HbA1c concentrations ranged from 7.5% to 9.5%.
They were randomized to receive placebo or remogliflozin in doses of 100, 250, 500, or 1,000 mg once daily, 250 mg twice daily, or pioglitazone, 30 mg once daily, for 3 months.
A total of 84% of patients completed the study.
Along with the 250 mg per day group, a significant change in HbA1c compared with placebo was seen for the 1,000 mg per day group, at minus 0.66% (95% CI minus 1.05-minus 0.28, P=0.001) and for 250 mg twice daily, at minus 0.59% (95% CI minus 0.97-minus 0.20, P=0.003).
"Clinically and statistically significant improvements in fasting plasma glucose concentrations, with changes from baseline at week 12 ranging from 0.85 to 1.06 mmol/L were also observed," the investigators reported.
Weight loss also was observed in all the remogliflozin groups except 100 mg once daily, with decreases ranging from 1.44 to 1.51 kg at 3 months.
None of the once-daily doses of the medication were associated with significant changes in total cholesterol, HDL or LDL cholesterol, or triglycerides. In the twice daily 250 mg dose, however, increases in LDL were seen. Increases in LDL have also been reported for dapagliflozin and canagliflozin, the researchers noted.
The overall rates of adverse events in the remogliflozin groups were 31% to 59%, and were 34% and 22%, respectively, in the pioglitazone and placebo groups.
The only adverse events that occurred in more than 10% of patients were dizziness, seen in 12% of patients receiving 250 mg once daily, and urinary tract infections, observed in 11% of the 1,000 mg once daily group.
Rates of "events of special interest," urinary tract infections and fungal genital infections, were low, although the genital infections occurred in 3% of the 250 and 500 mg once daily groups, in 6% of the 1,000 mg once daily group, and in 11% of the 250 mg twice daily group. None of the placebo or pioglitazone patients reported this type of infection.
Because the twice daily regimen was associated with a greater rate of fungal genital infection and increases in LDL, "limiting overnight inhibition of SGLT2" may limit these adverse events, according to the investigators.
- The investigational SGLT2 inhibitor remogliflozin etabonate showed significant benefits for glucose control among patients with type 2 diabetes.
- Clinically and statistically significant improvements in fasting plasma glucose concentrations, with changes from baseline at week 12 ranging from 0.85 to 1.06 mmol/L.
- Weight loss also was observed in all the remogliflozin groups except 100 mg once daily, with decreases ranging from 1.44 to 1.51 kg at 3 months.
Sykes A, et al "Randomized efficacy and safety trial of once-daily remogliflozin etabonate for the treatment of type 2 diabetes" Diabetes Obes Metab 2014; DOI: 10.1111/dom.12393.