Three SGLT2 inhibitors associated with decreased CVD risk in real-world setting
Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic)
A multinational observational analysisLiterature - Birkeland KI, Jørgensen ME, Carstensen B, et al. - Lancet Diabetes Endocrinol 2017; epub ahead of print
- Mean follow-up time was 0.9 years, with a total of 80,669 patient-years. The exposure time was about 18,000 years (94%) for dapagliflozin, 1000 years (5%) for empagliflozin and 250 years (1%) for canagliflozin.
- The HRs for CV mortality (0.53, 95% CI 0.40-0.71, P<0.0001), all-cause mortality (0.51, 95% CI 0.45-0.58, P<0.0001), MACE (0.78, 95% CI 0.69-0.87, P<0.0001), hospital events for HF (0.70, 95% CI 0.61-0.81, P<0.0001) and severe hypoglycemia (0.76, 95% CI 0.65-0.90, P=0.001) showed that new users of SGLT2 inhibitors were at reduced risk compared with new users of other glucose-lowering drugs.
- Non-fatal MI (HR 0.87, 95% CI 0.73-1.03, P=0.112), non-fatal stroke (HR 0.86, 95% CI 0.72-1.04, P=0.113) and AF (HR 0.95, 95% CI 0.84-1.08, P=0.456) did not differ significantly between the two groups.
- Only all-cause mortality showed significant heterogeneity in the size of the effect estimate between countries (P=0.002).
- In patients with and without CV disease (CVD) at baseline, SGLT2 inhibitors were associated with reduced risk of CV mortality (HR with 0.60, 95% CI 0.42-0.85 and HR without 0.55, 95% CI 0.34-0.90). However, for MACE, reduced associated risk was only present in patients with CVD at baseline (HR with 0.70, 95% CI 0.59-0.83, HR without 0.90, 95% CI 0.76-1.07).
- Neutral risk associations were found for both CV mortality and MACE in patients younger than 65 years (HR 1.10, 95% CI 0.65-1.84 and 1.01, 95% CI 0.85-1.20, respectively), whereas HRs were 0.45 (95% CI 0.32-0.65) and 0.66 (95% CI 0.56-0.78) respectively for patients of 65 years or older.
In a real-world clinical setting, new use of an SGLT2 inhibitor was associated with a decreased CVD and CV mortality risk compared with the new use of other glucose-lowering drugs in diabetic patients. This is consistent with results of CV outcome trials of drugs in this class. Moreover, as more than 90% of SGLT2 inhibitor exposure time was contributed by dapagliflozin, the finding lend support for a possible class effect, as findings were complementing to what has previously been shown in CV outcome trials with empagliflozin and canagliflozin. These findings could be useful for health-care practitioners treating diabetic patients at high CVD risk.