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New SGLT2 Inhibitor Likely to Be Approved for Type 2 Diabetes

Nov 14, 2014

Twice-daily regimen found to increase LDL, genital infections compared to benefits of once-daily regimen…

An investigational SGLT2 inhibitor remogliflozin etabonate showed significant benefits for glucose control in type 2 diabetics in a randomized study.

The study enrolled 241 participants with a mean age of 53, and who had a mean duration of diabetes of 2.5 years. The participants mean body mass index was 32 kg/m2 and a baseline hemoglobin (Hb) A1c range from 7.5%-9.5%.

Participants were randomized to receive placebo or remogliflozin in doses of 100, 250, 500, or 1000 mg once daily, 250mg twice daily, or pioglitazone 30mg daily for three months. A total of 84% patients completed the study, with two serious adverse events being reported, neither of which were treatment related.

The difference from placebo in HbA1c at 12 weeks with 250mg daily of remogliflozin was -0.56% (95% CI -0.95 to -0.16, p=0.006). In contrast, treatment with pioglitazone 30mg daily showed a difference from placebo of -0.19% (95% CI -0.58 to -0.20, p=0.337). A significant change was shown in the group taking 1000mg daily, -0.66% (95% CI -1.05 to -0.28, p=0.001) and for 250mg twice daily -0.59% (95% CI -0.97to -0.20, p=0.003).

“Clinically and statistically significant improvements were seen in fasting plasma glucose concentrations with changes from baseline at week 12 ranging from 0.85 to 1.06mmol/L were also observed,” investigators reported. Weight loss was reported in all the remogliflozin groups except 1000mg daily, with decreasing range from 1.44 to 1.51 kg at 3 months. None of the once-daily doses of medications were associated with significant changes in total cholesterol, HDL, LDL, or TG. In the twice-daily dosing of remogliflozin, increases in LDL were seen, which has also been the case for the two approved SGLT2 inhibitors dapagliflozin and canagliflozin.

The highest rate of genital infections were seen in the 250mg twice daily group at 11%, compared to 3% in the 250 & 500mg daily group and 6% in the 1000mg daily group. Overall, rates of urinary tract infections and fungal genital infections were low.

The twice-daily regimen associated with a higher rate of genital infections and increases in LDL may influence dosing in the future for this medication. However, investigators are optimistic that remogliflozin will continue to report beneficial outcomes.

Practice Pearls:

  • SGLT2 inhibitors are continuing to show beneficial effects in the treatment of type 2 diabetes.
  • A fourth SGLT2 inhibitor remogliflozin currently in clinical trials showed a significant reduction in HbA1c compared to placebo and observed weight loss.
  • Remogliflozin is another SGLT2 inhibitor in the pipeline for approval.

Diabetes, Obesity and Metabolism: 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.