Could Dapagliflozin Be Beneficial in The Treatment of Patients with Type 2 Diabetes and Multiple Risk Factors

What are the effects of prescribing sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes and multiple risk factors?

Type 2 diabetes (T2D) usually occurs with multiple risk factors and complications. When treating patients with T2D targeting several risk factors, especially in the early stages of the disease state, is of extreme importance. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been approved for the treatment of T2D since 2012. American Association of Clinical Endocrinologists (AACE) guideline recommends prescribing SGLT2 inhibitors as first-line treatment in patients with T2D and multiple risk factors (MRF) for atherosclerotic cardiovascular disease (ASCVD). SGLT2 inhibitors have been shown to significantly reduce the progression of end-stage renal disease by slowing the decline in eGFR. Over the last few years, accumulating data from cardiovascular and renal outcome trials of SGLT2 inhibitors has been a continual discussion and has demonstrated benefits in patients with T2D with MRF. Dapagliflozin is the only and first SGLT2 inhibitor approved by the FDA across the heart failure risk continuum. A study recently published by diabetes care analyzed the cardiovascular renal and metabolic effects of SGLT2 inhibitors in MRF patients.

In the DECLARE-TIMI 58, 17,160 individuals with T2D, men (55 years and older) and women (60 years and older), were randomly assigned to receive dapagliflozin 10mg daily or a placebo and followed for a median of 4.2 years. The trial included 40.6% with established ASCVD and 59.4% with MRF but without ASCVD. Patients with HbA1c of 6.5 to 12.0% and creatine clearance of 60ml/min or higher were eligible for inclusion. Participants in this primary prevention cohort had at least one additional cardiovascular risk factor, such as dyslipidemia, hypertension, or current tobacco use. The patients were treated according to the regional standards of care and guidelines for cardiovascular risk factors, blood pressure, lipids, antithrombotic treatment, and HbA1c.

Among the patients with MRF, the risk of the renal-specific outcome (hazard ratio (HR) 0.51, 95% CI 0.37–0.69) and cardiovascular death or hospitalization for heart failure (CVD/HHF) (HR 0.84, 95% CI 0.67–1.04) was reduced with dapagliflozin versus placebo, and it did not differ from that seen in patients with ASCVD. The effect on CVD/HHF was driven by a reduction in HHF in the MRF group. The benefits of dapagliflozin were observed in all clinically relevant subgroups with the MRF patients analyzed, including weight, systolic blood pressure, urinary albumin-to-creatinine ratio, and HbA1c versus placebo.

Clinical data of the large primary prevention population in the trial demonstrated a continual benefit of dapagliflozin versus placebo added to standard of care in reducing HbA1c, weight, and blood pressure in patients with type 2 diabetes. The trial highlighted the benefits of dapagliflozin in preventing HHF and renal-specific outcomes among patients with diabetes and multiple risk factors. Long-term benefits are expected by maintaining HbA1c reduction and reducing microvascular and macrovascular complications.

Practice Pearls:

• Dapagliflozin is beneficial for primary prevention in patients with T2D.
• In this study, dapagliflozin reduced the risk of cardiovascular death, hospitalization for heart failure, and adverse renal-specific outcomes in patients with T2D and multiple risk factors.
• Dapagliflozin’s overall favorable safety profile places it as an appropriate option for patients with T2D early in the disease.

Cahn, Avivit et.al. Cardiovascular, Renal, and Metabolic Outcomes of Dapagliflozin Versus Placebo in a Primary Cardiovascular Prevention Cohort: Analyses From DECLARE-TIMI 58. Diabetes care; 2 March 2021.

Brenda Oppong, PharmD Candidate, LECOM School of Pharmacy