Incidence of new-onset diabetes reduced by SGLT2 inhibitor
Dapagliflozin and new-onset type 2 diabetes in patients with chronic kidney disease or heart failure: pooled analysis of the DAPA-CKD and DAPA-HF trials
Introduction and methods
There is a need for effective and safe treatment to prevent diabetes and its complications. SGLT2 inhibitors were initially developed as glucose-lowering therapy for patients with type 2 diabetes (T2DM). Trials have demonstrated that these agents reduce risk of adverse CV events and kidney outcomes n T2DM patients. In addition, treatment with the SGLT2 inhibitors empagliflozin and dapagliflozin resulted in cardiorenal benefits in patients with heart failure or chronic kidney disease [1,2].
In this prespecified analysis of the DAPA-CKD trial and the DAPA-HF trial, pooled individual patient-level data were used to examined the effects of dapagliflozin on new-onset T2DM and the association with baseline characteristics was explored.
Data from DAPA-CKD and DAPA-HF trials were pooled. This analysis included 4003 participants who did not have T2DM at baseline (no previous diagnosis of T2DM or HbA1c ≥6.5%). Patients were classified as having prediabetes (HbA1c between 5.7%-6.4%) or normoglycemia (HbA1c <5.7%). Patients with randomized (1:1) to dapagliflozin or placebo. Median follow-up was 21.2 months (IQR 16.0-25.4).
Incidence of a new diagnosis of T2DM was a prespecified exploratory endpoint.
- There was minimal difference in mean Hb1Ac between participants who received dapagliflozin and those who received placebo (-0.01%, 95%CI: -0.03 to 0.01) at 12 months.
- In patients randomized to the dapagliflozin group, 4.3% of patients developed incident T2DM compared with 6.3% of patients in the placebo group (HR 0.67, 95%CI:0.51-0.88, P=0.0040).
- The difference between groups emerged after 4 months and persisted throughout follow-up.
- 6.8% Of patients in the dapagliflozin group with prediabetes at baseline developed diabetes vs. 9.7% of patients in the placebo group (HR 0.69, 95%CI:0.52-0.91, P=0.0097).
- The effect of dapagliflozin on risk of new-onset T2DM was similar across subgroups.
- Dapagliflozin was generally well tolerated in patients without T2DM at baseline.
This prespecified exploratory analysis of pooled data from the DAPA-CKD and DAPA-HF trials showed that in patients without T2DM at baseline, dapagliflozin reduced the incidence of new-onset T2DM.