SAN FRANCISCO — Empagliflozin used as monotherapy or as an add-on medication improved outcomes for patients with type 2 diabetes, according to research presented at the American Diabetes Association’s 74th Scientific Sessions.
Findings presented by both Michael Roden, MD, of the Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, and Martin Ridderstråle, MD, of the Steno Diabetes Center, Denmark, demonstrated the treatment was safe and effective.
Monotheraphy, compared with sitagliptin
Roden and colleagues conducted a phase III, double-blind, 52-week extension trial comparing different doses of empagliflozin (EMPA) monotherapy against placebo and sitagliptin (SITA) in patients not already receiving treatment.
“In drug-naive patients with type 2 diabetes, treatment with empagliflozin in 10 mg or 25 mg for 76 weeks led to sustained reductions in HbA1c vs. placebo, in body weight vs. placebo as well as sitagliptin and in systolic blood pressure vs. placebo as well as sitagliptin,” Roden said during his presentation.
Of 899 patients (551 men) in the initial 24-week study, 615 continued treatment into phase III; these participants maintained comparable characteristics. The initial group had been randomized at baseline to either EMPA 10 mg (n=224), EMPA 25 mg (n=224), placebo (n=228) or SITA 100 mg (n=223), with mean exposure of 14.2, 17, 16.7 and 16.2 months, respectively.
At week 76, EMPA 10 mg and 25 mg had significantly reduced HbA1c compared with PBO (-0.89% and -0.66%) as well as body weight (-2 kg and .5 kg); clinically meaningful and sustained reductions in SBP were also observed with the EMPA treatments (-3.4 mmHg and 0.4 mmHg).
Adverse reactions including hypoglycemic events (glucose ≤70 mg/dL and/or requiring assistance) and urinary tract infection were similar with EMPA, PBO and SITA; more patients reported reactions consistent with genital infection with EMPA than PBO or SITA.
“Empagliflozin was well-tolerated,” Rosen said, “and empagliflozin at the higher dose reduced HbA1c also when compared to sitagliptin at the end of the intervention period.”
Add-on to metformin vs. glimepiride add-on
In another phase 3, double-blind study, Ridderstråle and colleagues compared EMPA with glimepiride (GLIM) as an add-on medication for patients with type 2 diabetes already receiving Metformin; the 12-week study completed a 2-year trail.
The investigators assigned patients to EMPA 25mg (n=765) once daily or a stepwise up-titration scheme of GLIM 1-4 mg (n=780) once daily. Patients were 55% male (mean age, 56; BMI 30.1 ± 5.3 kg/m and HbA1c just below 8%).
Endpoints considered were changes from baseline in HbA1c, weight and systolic and diastolic blood pressure (SBP and DBP) and occurrence of hypoglycemic adverse events (glucose ≤70 mg/dL and/or requiring assistance).
“Empagliflozin, when added to Metformin, provided a sustained reduction in HbA1c with a statistically significant difference compared with glimepiride and with a low risk of hypoglycemia,” Ridderstråle said during his presentation. “Treatment with empagliflozin as an add-on to metformin led to sustained body weight and blood pressure reductions compared with glimepiride and was well tolerated.”
At the end of the study, there was significant decrease in HbA1c with EMPA compared with GLIM (-.66% vs. -.55%). “This met the non-inferiority and also the superiority criteria,” Ridderstråle said.
Hypoglycemic events were reported in 2.5% of patients on EMPA and 24.2% on GLIM (RR=0.102; 95% CI, 0.065-0.162), with 2 patients on GLIM requiring assistance.
Significant reductions were seen with EMPA compared with GLIM in weight (-3.1 kg vs. 1.3 kg) as well as in SBP (-3.1 mmHg vs. 2.5 mmHg) and DBP (−1.8 mmHg vs. 0.9 mmHg)
Adverse events consistent with urinary tract infection were similar with EMPA and GLIM; however events consistent with genital infection were reported more with EMPA than GLIM (11.8% vs. 2.2%).
Baseline data for the original trial were published a year ago, Ridderstråle said; the results presented at ADA’s 74th Scientific Sessions are available online in The Lancet Diabetes & Endocrinology.
For More Information: Roden M. Abstract 264-OR. Presented at: American Diabetes Association’s 74th Scientific Sessions; June 13-17, 2014; San Francisco.
Ridderstråle M. Abstract 266-OR. Presented at: American Diabetes Association’s 74th Scientific Sessions; June 13-17, 2014; San Francisco.
Ridderstråle et al. Lancet Diabetes Endocrinol. 2014;doi:10.1016/S2213-8587(14)70120-2.
Roden reports serving on the advisory panel and speaker’s bureau for Eli Lilly and Company, Novo Norodisk, Inc. and Takeda Pharmaceutical Company, Ltd; being a consultant for Sanofi; and receiving research support from Boehringer Ingelheim Pharmaceuticals, Inc. and Novartis Pharmaceuticals Corporation.
Ridderstråle reports serving on the speaker’s bureau for from Boehringer Ingelheim Pharmaceuticals, Inc., Novartis Norodisk, Inc., Sanofi-Aventis, Novartis Pharmaceuticals Corporation, Eli Lilly and Company, Roche Pharmaceuticals, Johnson & Johnson, Merck & Co., Metronic and GlaxoSmithKline, and being a board member for Novartis Norodisk, Inc., Medtronic and Boehringer Ingelheim Pharmaceuticals, Inc.