Following the results of the EMPA-REG OUTCOME trial with empagliflozin, is it possible to speak of a class effect?

BACKGROUND: The recently published cardiovascular outcomes data for the first sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, have shown cardiovascular safety and additional benefits in patients with type 2 diabetes and established cardiovascular disease. Empagliflozin showed lower rates of death from cardiovascular causes or from any causes and lower hospitalization rates from heart failure compared with placebo, both in addition to standard care. This commentary discusses the existence of a possible class effect considering the available evidence described for other SGLT2 inhibitors. MAIN TEXT: Empagliflozin, dapagliflozin and canagliflozin share the same mechanism of action, and it is a plausible hypothesis that some of the benefits of empagliflozin treatment could also be expected from other SGLT2 inhibitors. However, the rapid and persistent occurrence of cardiovascular benefits observed with empagliflozin and the different results shown by the three inhibitors in meta-analyses of some of their respective Phase II and III trials might suggest another possible mechanism of action, perhaps related to the different selectivity to inhibit SGLT-2 and other SGLT family members that these compounds present. CONCLUSION: There is still lack of evidence to answer whether the cardiovascular benefits observed with empagliflozin in the EMPA-REG OUTCOME study could be seen as a "class effect", which is also attributable to dapagliflozin and canagliflozin.

Eficacia y seguridad de empagliflozina en combinación con otros hipoglucemiantes orales en pacientes con diabetes mellitus tipo 2 / Efficacy and safety of empagliflozin in combination with other oral hypoglycemic agents in patients with type 2 diabetes mellitus

Introducción: Analizar la eficacia y la seguridad de empagliflozina en combinación con otros hipoglucemiantes orales en pacientes con diabetes mellitus tipo 2. Métodos: Análisis de 3 ensayos fase III en pacientes con diabetes mellitus tipo 2 (n=1.801) que recibieron placebo, empagliflozina 10 o 25mg, una vez al día, durante 24 semanas, en combinación con metformina, metformina+sulfonilurea o pioglitazona±metformina. Resultados: Empagliflozina redujo significativamente la HbA1c (reducción media ajustada vs. placebo con empagliflozina 10 mg: -0,58% [IC 95%: -0,66; -0,49]; p < 0,0001 y con empagliflozina 25 mg -0,62% [IC 95%: -0,70; -0,53], p<0,0001), el peso (reducción media ajustada vs. placebo con empagliflozina 10 mg: -1,77kg [IC 95%: -2,05; -1,48]; p < 0,0001 y con empagliflozina 25 mg: -1,96 kg [IC 95%: -2,24; -1,67], p < 0,0001) y la presión arterial sistólica y diastólica. La frecuencia de efectos adversos fue del 64% con placebo, del 63,9% con empagliflozina 10 mg y del 60,9% con empagliflozina 25 mg. Las hipoglucemias confirmadas (menor o igual a 70 mg/dl y/o requiriendo asistencia) ocurrieron en un 3,9% de los pacientes con placebo, un 6,9% con empagliflozina 10 mg y un 5,3% con empagliflozina 25 mg. Las infecciones del tracto urinario acontecieron en un 9,4% con placebo, un 10,2% con empagliflozina 10 mg y un 8,3% con empagliflozina 25 mg. Las infecciones genitales se comunicaron en un 1,0% de los pacientes con placebo, un 4,6% con empagliflozina 10 mg y un 3,5% con empagliflozina 25 mg. Conclusiones: Empagliflozina en combinación con otros tratamientos orales vs. placebo disminuyó significativamente la HbA1c, el peso corporal y la presión arterial sistólica/diastólica, con un buen perfil de seguridad y tolerancia (AU)

Introduction: To analyze the efficacy and safety of empagliflozin combined with other oral hypoglycemic agents in patients with type 2 diabetes mellitus. Methods: Pooled analysis of three phase III trials in patients with type 2 diabetes mellitus (n=1,801) who received placebo or empagliflozin 10 or 25 mg once daily for 24 weeks, in combination with metformin, metformin+sulphonylurea or pioglitazone ± metformin. Results: Empagliflozin significantly decreased HbA1c (adjusted mean reduction vs placebo with empagliflozin 10mg: -0.58% [95% CI: -0.66; -0.49]; P<.0001, and with empagliflozin 25 mg: -0.62% [95% CI: -0.70; -0.53], P<.0001), weight (adjusted mean reduction vs placebo with empagliflozin 10 mg: -1.77 kg [95% CI: -2.05; -1.48]; P <.0001, and with empagliflozin 25mg: -1.96kg [95% CI: -2.24; -1.67], P<.0001), and systolic and diastolic blood pressure (SBP/DBP). Adverse effect rates were 64% with placebo, 63.9% with empagliflozin 10 mg, and 60.9% with empagliflozin 25 mg. Documented episodes of hypoglycemia (is less than or equal to 70 mg/dL and/or requiring care) occurred in 3.9% of patients with placebo, 6.9% of patients with empagliflozin 10 mg, and 5.3% of patients with empagliflozin 25 mg. Urinary tract infections developed in 9.4% of patients with placebo, 10.2% of patients with empagliflozin 10 mg, and 8.3% of patients with empagliflozin 25 mg. Genital infections were reported in 1.0% of patients with placebo, 4.6% of patients with empagliflozin 10mg, and 3.5% of patients with empagliflozin 25 mg. Conclusions: Empagliflozin combined with other oral treatments decreased HbA1c, body weight, and SBP/DBP as compared to placebo, with a good safety and tolerability profile (AU)

Efficacy and safety of empagliflozin in combination with other oral hypoglycemic agents in patients with type 2 diabetes mellitus. / Eficacia y seguridad de empagliflozina en combinación con otros hipoglucemiantes orales en pacientes con diabetes mellitus tipo 2.

INTRODUCTION: To analyze the efficacy and safety of empagliflozin combined with other oral hypoglycemic agents in patients with type 2 diabetes mellitus. METHODS: Pooled analysis of three phase III trials in patients with type 2 diabetes mellitus (n=1,801) who received placebo or empagliflozin 10 or 25mg once daily for 24 weeks, in combination with metformin, metformin+sulphonylurea or pioglitazone ± metformin. RESULTS: Empagliflozin significantly decreased HbA1c (adjusted mean reduction vs placebo with empagliflozin 10mg: -0.58% [95% CI: -0.66; -0.49]; P<.0001, and with empagliflozin 25mg: -0.62% [95% CI: -0.70; -0.53], P<.0001), weight (adjusted mean reduction vs placebo with empagliflozin 10mg: -1.77kg [95% CI: -2.05; -1.48]; P<.0001, and with empagliflozin 25mg: -1.96kg [95% CI: -2.24; -1.67], P<.0001), and systolic and diastolic blood pressure (SBP/DBP). Adverse effect rates were 64% with placebo, 63.9% with empagliflozin 10mg, and 60.9% with empagliflozin 25mg. Documented episodes of hypoglycemia (≤70mg/dL and/or requiring care) occurred in 3.9% of patients with placebo, 6.9% of patients with empagliflozin 10mg, and 5.3% of patients with empagliflozin 25mg. Urinary tract infections developed in 9.4% of patients with placebo, 10.2% of patients with empagliflozin 10mg, and 8.3% of patients with empagliflozin 25mg. Genital infections were reported in 1.0% of patients with placebo, 4.6% of patients with empagliflozin 10mg, and 3.5% of patients with empagliflozin 25mg. CONCLUSIONS: Empagliflozin combined with other oral treatments decreased HbA1c, body weight, and SBP/DBP as compared to placebo, with a good safety and tolerability profile.