Dapagliflozin Linked to Reduction in Incidence of Type 2 Diabetes

Peter Rossing, MD

Previous data from the DAPA-HF trial show that dapagliflozin decreased incidence of new-onset type 2 diabetes by 32% compared to placebo in a cohort of patients without type 2 diabetes (T2D).

Further studies, including the DAPA-CKD trial, demonstrated a significant reduction in the risk of adverse kidney and cardiovascular outcomes in participants with and without T2D after dapagliflozin reduced the risk of kidney failure and cardiovascular (CV) death.

In a new analysis presented at the 2021 American Diabetes Association Virtual Meeting, treatment with dapagliflozin showed significant reduction in risk of adverse kidney and CV outcomes in patients with chronic kidney disease (CKD), with or without T2D.

Study

Investigators, led by Peter Rossing, MD, Steno Diabetes Center Copenhagen, performed a pre-specified analysis of patients with no history of diabetes and HbA1c <6.5% at baseline.

The outcome included incident type 2 diabetes or an HbA1c value of ≥6.5% measured in a laboratory at 2 consecutive study visits.

Inclusion criteria included ≥18 years, eGFR 25 - 75 mL/min/1.73 m2, UACR 200 - 500 mg/g, and stable maximum tolerated labeled dose of ACEi or ARB for ≥4 weeks.

Further, exclusion included patients with type 1 diabetes, polycystic kidney disease, lupus nephritis, ANCA-associated vasculitis, and immunosuppressive therapy within 6 months prior to enrollment.

During screening, a total of 2152 patients were included in the dapagliflozin 10 mg once daily group and 2152 patients were matched in the placebo.

Investigators assessed new onset T2D and comparison between the 2 groups through Cox proportional hazard models.

Results

Data show 32% of patients (n = 1398) had no history of T2D, with HbA1c <6.5% at baseline.

In the placebo group, 4.7% of patients experienced new-onset T2D, while 3.0% had new-onset T2D in the dapagliflozin group.

Of patients with new-onset T2D (n = 9), data show patients had a mean age of 62 years, 35% female, with a mean HbA1c of 6.2 mmol/mol and mean UACR of 1249 mg/g.

Investigators observed a cumulative incidence of new-onset T2D with a hazard ratio of 0.62 (95% CI, 0.36 - 1.08).

Data show T2D developed in 33 of 701 patients (4.7%) in the placebo group, while it developed in 21 of 697 patients (3.0%) in the dapagliflozin group.

As a result, it led to event rates of 2.4/100 patient-years in placebo and 1.5/100 patient-years in dapagliflozin.

The team observed a 38% reduction in T2D incidence with dapagliflozin (HR 0.62, 95% CI, 0.36 - 1.08).

Further, they noted the effect of dapagliflozin had consistent outcomes across subgroups, including age, glycemic status, blood pressure, eGFR, albuminuria, race, and region, with more effect in female patients (P = .03).

In addition, over 90% of participants who developed T2D had prediabetes at study baseline with an HbA1c of 5.7 - 6.4%.

In a meta-analysis of DAPA-CKD and DAPA-HF, dapagliflozin was shown to reduce new-onset diabetes compared to placebo (HR 0.66, 95% CI, 0.51 - 0.87, P = .003).

Conclusion

Investigators concluded the findings were consistent with previous results from the DAPA-HF trial.

“Dapagliflozin was well tolerated,” investigators wrote. “There were fewer serious adverse events with dapagliflozin than placebo with new-onset type 2 diabetes.”

The study, “Dapagliflozin and the Incidence of Type 2 Diabetes Patients with Chronic Kidney Disease,” was published online by ADA.