SGLT-2 inhibitors tied to better CV outcomes vs DPP-4 inhibitors

Patients with type 2 diabetes (T2D) who initiated SGLT2* inhibitors (SGLT2is) had better cardiovascular (CV) outcomes than those on DPP-4** inhibitors, shows the large, global, real-world study, CVD-REAL 2. 

Initiation of SGLT2is was associated with significantly reduced risk across multiple CV outcomes including heart failure, mortality, myocardial infarction (MI), and stroke compared with DPP-4 inhibitors. [Lancet Diabetes Endocrinol 2020;8:606-615]

These data, according to the researchers, fill the knowledge gap on the comparative effectiveness of SGLT2is vs DPP-4 inhibitors across a broad range of CV risk — in view of the absence of a head-to-head randomized trial directly comparing the two newer classes of antidiabetic drugs. 

Also, this study extends the CV benefits seen with the use of SGLT2s in previous large-scale placebo-randomized CV outcome trials to real-world clinical practice, the researchers highlighted.

“Despite variable patient characteristics, healthcare settings, practice patterns, and specific SGLT2i drugs used, the directions of associations were consistent across countries and regions and across the subgroups with or without previous CV disease,” they pointed out.

“Clinicians can be confident that prescribing a SGLT2i will, on average, provide more CV benefits than prescribing a DPP-4 inhibitor,” wrote Dr Hertzel Gerstein from McMaster University and Hamilton Health Sciences in Hamilton, Canada, in a linked commentary. [Lancet Diabetes Endocrinol 2020;8:557-558]

CV benefits for REAL

In the large, global, population-based, observational comparative study, more than 386,000 T2D patients (mean age 58 years, 44.1 percent women, 30.1 percent with established CV disease) across 13 countries who initiated either an SGLT2i or a DPP-4 inhibitor were propensity score-matched in a 1:1 ratio.

The SGLT2i cohort had substantially lower risk in the composite of hospitalization for heart failure (HHF) and all-cause mortality (hazard ratio [HR], 0.64; p<0.0001) than the DPP-4 inhibitor cohort.

Similarly, the individual components of HHF (HR, 0.69; p<0.0001) and all-cause mortality (HR, 0.59; p<0.0001) were also substantially reduced in the cohort who initiated SGLT2i vs DPP-4 inhibitor.

While reductions in the risk of MI (HR, 0.88; p=0.020) and stroke (HR, 0.85; p=0.0004) were less, the difference remained significant in favour of the SGLT2i cohort.

“Our findings are in line with … and complement those of randomized controlled trials [RCTs], which did not include head-to-head comparisons of SGLT2is and DPP-4 inhibitors,” said the researchers.

The SGLT2is in the study included canagliflozin, dapagliflozin, empagliflozin, ipragliflozin, tofogliflozin, and luseogliflozin.

Reassuring data

While both SGLT2is and DPP-4 inhibitors have previously been shown to reduce HbA1c, no CV benefits in terms of major adverse CV events or HHF have been shown in RCTs of DPP-4 inhibitors whereas a consistent decrease in HHF risk was seen in all CV outcome trials of SGLT2is.

“The fact that the findings are consistent with these trials reassures clinicians and the people who pay for healthcare that the clinical trials, which were done in a highly selected population, are generalizable to the so-called average patient with T2D,” wrote Gerstein.

“SGLT2 inhibitors and DPP-4 inhibitors are widely used in everyday clinical practice, and healthcare practitioners and patients should be aware of the comparative effectiveness of these two drug classes, including with respect to CV outcomes associated with the use of these agents,” the researchers added.

As they noted, SGLT2i initiation was associated with CV benefits even in a subgroup of participants without established CV disease. 

“Our results suggest that the CV benefits of SGLT2is might be applicable to a broader patient population than previously considered,” the researchers suggested.