Empagliflozin and Microvascular Outcomes in EMPA-REG OUTCOME
Author Block: CHRISTOPH WANNER, CHRISTOPHER LEE, HANS J. WOERLE, MICHAELA MATTHEUS, SILVIO E. INZUCCHI, BERNARD ZINMAN, Würzburg, Germany, Ingelheim, Germany, New Haven, CT, Toronto, ON, Canada
In EMPA-REG OUTCOME, empagliflozin, given at a dose of 10 mg or 25 mg in addition to standard of care, reduced the risk of cardiovascular (CV) outcomes vs. placebo (PBO) in patients with type 2 diabetes (T2DM) and high CV risk. We investigate the effect of empagliflozin on microvascular outcomes.
A pre-specified composite microvascular outcome was defined as time to first initiation of laser therapy for retinopathy, vitreous hemorrhage, diabetes-related blindness, or new or worsening nephropathy (defined in Table).
Results
7020 patients were included in the intent-to-treat analysis. Median observation time was 3.1 years. Mean HbA1c (%) was 8.08, 8.07 and 8.08 at baseline and 7.93, 7.81 and 8.16 (adjusted) at week 208 for empagliflozin 10 mg, 25 mg and PBO, respectively. The composite microvascular outcome occurred in a significantly lower percentage of patients on empagliflozin (pooled; 14.0%) than PBO (20.5%; hazard ratio [HR] 0.62 [95% CI 0.54, 0.70]; p<0.001). HR (95% CI) with empagliflozin versus PBO was 0.69 (0.43, 1.12) (p=0.134) for initiation of laser therapy for retinopathy; 0.93 (0.51, 1.71) (p=0.815) for vitreous hemorrhage; 0.61 (0.53, 0.70) (p<0.001) for new or worsening nephropathy.
Conclusion
Empagliflozin used in addition to standard of care reduced the risk of a composite microvascular outcome in patients with T2DM and high CV risk, driven by a reduction in new or worsening nephropathy.OutcomePlaceboEmpagliflozinHazard ratio
(95% CI) p-valuen/N
(%)Rate/
1000
pt-yearsn/N
(%)Rate/
1000
pt-yearsComposite microvascular outcome424/2068 (20.5)83.6577/4132 (14.0)52.80.62
(0.54, 0.70)<0.001Initiation of laser therapy for retinopathy29/2333
(1.2)4.441/4687
(0.9)3.00.69
(0.43, 1.12)0.134Vitreous hemorrhage16/2333
(0.7)2.430/4687
(0.6)2.20.93
(0.51, 1.71)0.815Diabetes-related blindness†2/2333
(0.1)0.34/4687
(0.1)0.3--New or worsening nephropathy388/2061
(18.8)76.0525/4124 (12.7)47.80.61
(0.53, 0.70)<0.001New onset of macroalbuminuria330/2033 (16.2)64.9459/4091 (11.2)41.80.62
(0.54, 0.72)<0.001Doubling of serum creatinine*60/2323
(2.6)9.770/4645
(1.5)5.50.56
(0.39, 0.79)<0.001Initiation of continuous renal replacement therapy14/2333
(0.6)2.113/4687
(0.3)1.00.45
(0.21, 0.97)0.041Death due to renal disease†0/2333
(0.1)0.2--Cox regression analysis in patients treated with ≥1 dose of study drug.
*Accompanied by estimated glomerular filtration rate (Modification of Diet in Renal Disease formula) ≤45 ml/min/1.73m2.
†Hazard ratio and 95% CI were not analyzed as the total number of events was <14.
Authors: CHRISTOPH WANNER, CHRISTOPHER LEE, HANS J. WOERLE, MICHAELA MATTHEUS, SILVIO E. INZUCCHI, BERNARD ZINMAN, Würzburg, Germany, Ingelheim, Germany, New Haven, CT, Toronto, ON, Canada
Another presentation showed no negative effects on fractures
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