SGLT-2 inhibitors promising option for CVD prevention in diabetes patients regardless of NAFLD status: JAMA

In the population-based cohort study, GLP-1 receptor agonists and SGLT-2 inhibitor therapy were associated with reduced risk of major adverse cardiovascular events in patients with type 2 diabetes and across baseline NAFLD status. SGLT-2i therapy was also associated with a reduced risk of hospitalization for heart failure.

Nonalcoholic fatty liver disease (NAFLD) is a cardiovascular risk factor, but it is uncertain whether glucagon-like peptide-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors are associated with reduced cardiovascular risk in patients with type 2 diabetes (T2D) and concomitant NAFLD remains uncertain. Therefore, Sungho Bea, School of Pharmacy, Sungkyunkwan University, Suwon, South Korea, and colleagues aimed to investigate the outcomes of SGLT-2i and GLP-1RA therapy among T2D patients varied by the absence or presence of NAFLD.

For this purpose, the researchers performed a retrospective, population-based, nationwide cohort study using an active-comparator new-user design. Two distinct new-user active-comparator cohorts of patients aged 40 and above who initiated GLP-1 receptor agonists or SGLT2 inhibitors were propensity score-matched to patients who initiated dipeptidyl peptidase-4 inhibitors (DPP-4i).

The main outcomes were (1) major adverse cardiovascular events (MACE), a composite endpoint of hospitalization for stroke, hospitalization for myocardial infarction (MI), and cardiovascular death, and (2) hospitalization for heart failure (HHF). Cox proportional hazard models were used to estimate hazard ratios (HRs). The Wald test was applied to evaluate heterogeneity by NAFLD.

The researchers reported the following findings:

• After 1:1 propensity score matching, 140 438 patients were retrieved in the first cohort (SGLT-2i vs DPP-4i; mean age, 57.5 years; 56.7% male) and 34 886 patients were identified in the second cohort (GLP-1RA vs DPP-4i; mean age, 59.5 years; 51.3% male).
• Compared with DPP-4i, SGLT-2i therapy was associated with a lower risk of MACE (HR, 0.78) and HHF (HR, 0.62).
• GLP-1RA therapy was associated with a decreased risk of MACE (HR, 0.49) but had statistically nonsignificant findings regarding HHF (HR, 0.64).
• Stratified analysis by NAFLD status yielded consistent results for SGLT-2i (MACE with NAFLD: HR, 0.73; without NAFLD: HR, 0.81; HHF with NAFLD: HR, 0.76; without NAFLD: HR, 0.56) and for GLP-1RA (MACE with NAFLD: HR, 0.49; without NAFLD: HR, 0.49; HHF with NAFLD: HR, 0.82; without NAFLD: HR, 0.54).

“These results support the current guidelines that recommend GLP-1 receptor agonists as the first line of therapy for patients with T2D and NAFLD,” the researchers wrote.

They added, “Furthermore, this study highlights the potential of SGLT-2i as a promising option for CVD prevention regardless of NAFLD status.”

Reference:

Bea S, Jeong HE, Filion KB, et al. Outcomes of SGLT-2i and GLP-1RA Therapy Among Patients With Type 2 Diabetes and Varying NAFLD Status. JAMA Netw Open. 2023;6(12):e2349856. doi:10.1001/jamanetworkopen.2023.49856