SGLT-2is yield more CV benefits than GLP-1 RAs in real-world study

SGLT-2* inhibitors may confer more cardiovascular (CV) protective benefits than GLP-1 RAs** in patients with type 2 diabetes (T2D), according to a real-world study presented at the EASD 2020 virtual Congress.   

“According to ADA/EASD consensus statements, GLP-1 RAs should be preferred for patients with or at high risk of atherosclerotic CV disease, whereas SGLT-2 inhibitors are preferred when heart failure [HF] or chronic kidney disease predominates” said presenting author Dr Gian Paolo Fadini from University Hospital of Padova, Padua, Italy.

While meta-analyses pooling data from multiple studies have shown greater benefit with SGLT-2 inhibitors in reducing the risk of hospitalization for HF than GLP-1 RAs or placebo, a head-to-head trial directly comparing the CV effects of the two drug classes is still lacking.

“In the absence of a head-to-head comparative trial, our observational real-word data suggest that SGLT-2 inhibitors may be more effective than GLP-1 RAs in improving CV outcomes of T2D,” said Fadini.

Over a median follow-up of 13–18  months, the rates of the primary composite outcome of 3-point MACE*** comprising all-cause death, myocardial infarction (MI), and stroke were lower among T2D patients who initiated SGLT-2 inhibitors vs GLP-1 RAs (hazard ratio [HR], 0.78; p=0.043). [EASD 2020, abstract 121]

New users of SGLT-2 inhibitors also had lower risks of MI (HR, 0.72; p=0.035), hospitalization for HF (HR, 0.59; p=0.048), and hospitalization for CV causes (HR, 0.82; p=0.037) than those on GLP-1 RAs.  

When the analysis was stratified by the presence of established CV disease at baseline, initiating SGLT-2 inhibitors was associated with a reduced risk of 3-point MACE compared with GLP-1 RAs, especially among patients with established CV disease at baseline (HR, 0.70; p=0.049).

In addition, SGLT-2 inhibitors were also associated with a lower risk of hospitalization for HF vs GLP-1 RAs, in particular among patients without pre-existing CV disease (HR, 0.39; p=0.048).

“The finding on HF was consistent with the literature, suggesting that SGLT-2 inhibitors protect from hospitalization for HF more than GLP-1 RAs,” Fadini noted.

“[On the other hand,] the better MACE outcomes in patients treated with SGLT-2 inhibitors vs GLP-1 RAs was unexpected, though the anti-atherosclerotic effects of SGLT-2 inhibitors have been supported by preclinical studies,” he added.

Among a subgroup of patients with available data on biochemical measures (n=800 for GLP-1 RAs users; n=982 for SGLT-2 inhibitor users), the reduction in HbA1c was greater with GLP-1 RAs vs SGLT-2 inhibitors, while the improvements in systolic blood pressure and HDL cholesterol were better with SGLT-2 inhibitors than GLP-1RAs.

“Although there were no significant differences between the two classes in terms of adverse events, there was a trend towards lower renal events with SGLT-2 inhibitors than GLP-1 RAs — in line with data from randomized clinical trials [RCTs] and observational studies,” reported Fadini.

The retrospective real-world study involved 12,996 patients (mean age 63 years, 63 percent male) with T2D who initiated either SGLT-2 inhibitors (n=7,192) or GLP-1 RAs (n=5,804) and were matched 1:1 based on propensity scores.

Due to the nonrandomized nature of study design, observational studies are intrinsically biased with confounding by indication, and thus, cannot provide the same level of evidence as RCTs, Fadini explained. However, these data can provide valuable information to support clinical decision in the absence of RCTs.

“Our findings may represent moderate evidence to guide the coalition on the choice of treatment to reduce the risk of CV disease in patients with T2D,” stated Fadini.