SGLT2 inhibition may improve survival of high risk T2DM patients
Long-Term Benefit of Empagliflozin on Life Expectancy in Patients With Type 2 Diabetes Mellitus and Established Cardiovascular Disease: Survival Estimates From the EMPA-REG OUTCOME Trial
Introduction and methods
In patients with type 2 diabetes mellitus (T2DM) and established CVD, empagliflozin, on top of standard of care, reduced the risk of CV death by 38% and all-cause mortality by 32% over a median observation period of 3.1 years . In this actuarial analysis of data from the EMPA-REG OUTCOME trial , the long-term benefit of empagliflozin on the residual life span was estimated.
In the EMPA-REG OUTCOME trial, 7,020 patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo. For this analysis, complete follow-up data from all treated patients were used to estimate the effect of empagliflozin versus placebo on all-cause mortality over the duration of patients’ lifetimes using patient age as the time scale (rather than time since randomization). Actuarial estimates of the age-specific probabilities of death were produced for the empagliflozin and placebo-treated groups. For patients in each treatment group at each year of age, the expected residual years of survival were estimated as the area under the survival curve. As a consequence of randomization, patient age and treatment do not depend on each other, and therefore the difference in the areas under the survival curve can be interpreted as the effect of treatment on time spent event-free.
The estimated mean survival by age was:
- at age 45: 32.1 years with empagliflozin versus 27.6 years with placebo (difference: 4.5 years; 95%CI: 1.3–7.8; P=0.007)
- at age 50: 28.5 versus 25.4 years (difference: 3.1 years; 95%CI: 0.9–5.3; P=0.005)
- at age 60: 21.8 versus 19.2 years (difference: 2.5 years; 95%CI: 1.1–3.9; P=0.001)
- at age 70: 14.8 versus 12.8 years (difference: 2.0 years; 95%CI: 0.7–3.2; P=0.003)
- at age 80: 7.7 versus 6.7 years (difference: 1.0 year; 95%CI: −0.3 to 2.2; P=0.13)
- The relative increases in mean survival were consistent regardless of age, ranging between 12% and 15%.
Applying actuarial methods on EMPA-REG OUTCOME data and assuming that the beneficial effects of empagliflozin remain consistent with long-term use, suggests that the estimated survival of T2DM patients with established CVD improves with empagliflozin versus placebo by 1 to 5 years.