Background:
Many patients with type 2 diabetes (T2D) will, over time, require insulin therapy for glycemic control. Treatment-attendant adverse effects of insulin such as weight gain and hypoglycemia may be especially problematic in those with CVD. Delaying the need for insulin initiation may therefore be an important therapeutic goal, especially in those with CVD.
Methods:
This actuarial analysis evaluated the 3,633 (52%) of 7,020 EMPA-REG OUTCOME participants who were not using insulin at baseline. Patients were randomized to the SGLT2 inhibitor empagliflozin (EMPA) 10mg, 25mg, or placebo (PBO). After the first 12 weeks, changes in background antihyperglycemic therapy were allowed. We estimated survival time free from insulin initiation (sustained over ≥2 consecutive study visits) over patients’ lifetimes by using baseline age as the time horizon. Age-based Kaplan-Meier survival curves were constructed for each year of age between 45 and 80 years. Differences in area under the survival curve between treatment arms represented treatment effects on time spent alive and free from insulin initiation.
Results:
During median follow-up of 3.2 years, insulin was required in 172 patients (7.1%) with EMPA and 196 (16.4%) with PBO. Lifetime benefits on insulin-free survival were inversely related to baseline age, ranging from 1.4 to 11.3 years. For a 45-year-old, estimated insulin-free survival was 20.1 years with EMPA and 10.0 years with PBO (difference: 10.1 years; 95% CI 5.7-14.5 years; P<0.0001). At age 60 years, insulin-free survival was 16.7 vs. 10.5 years (difference: 6.2 [4.6-7.8]; P<0.0001), and at age 75 years, 9.7 vs. 8.1 years (difference: 1.5 [0.0-3.1]; P=0.056).
Conclusions:
Assuming stable lifetime effects, we estimate that initiation of EMPA prolongs time alive free from need for insulin by 1.4 to over 11 years among adults with T2D and CVD. While benefits were most pronounced among younger patients, EMPA reduced the need for insulin across a broad age range.