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SGLT2 Inhibitors Cut Cardiovascular Risk in Diabetes, Even in Low-risk Populations


The new report compared the benefits of sodium-glucose co-transporter 2 (SGLT2) inhibitors with those of other glucose-lowering drugs and found lower rates of heart disease and mortality.

A new observational study shows that sodium-glucose co-transporter 2 (SGLT2) inhibitors are associated with reduced risk of cardiovascular mortality, heart failure, and chronic kidney disease in patients with type 2 diabetes.

The report helps clarify the benefits associated with SGLT2 inhibitors, which have previously been linked with reduced cardiovascular risks, vs the benefits of other glucose-lowering drugs. The study was published in the journal Cardiovascular Diabetology.

The authors explained that cardiovascular problems are a major cause of morbidity and mortality among patients with type 2 diabetes, who have an estimated 2- to 4-fold heightened risk of coronary heart disease.

Existing evidence has supported the use of SGLT2 inhibitor therapy to mitigate the increased risk, but the study investigators wrote that previous studies included a number of variables, such as different treatment initiation times and different regions, prompting the authors to want to examine the benefits of SGLT2 inhibitors vs other glucose-lowering drugs in a large cohort of patients all within the same region: Catalonia, in Spain.

The study looked at 2 cohorts of 12,197 patients who received treatment between 2013 and 2016. One cohort included new users of SGLT2 inhibitors; the second cohort was made up of new users of other glucose-lowering drugs. About one-quarter (27%) of people in the study had a previous history of cardiovascular disease.

Over the course of the study, participants in the SGLT2 inhibitor group had an overall exposure of 9484 patient-years. Most of those patient-years were spent taking dapagliflozin (Farxiga), with smaller proportions of patients being prescribed empagliflozin (Jardiance) and canagliflozin (Invokana).

Patients in the other glucose-lowering drug cohort had 10,012 years of exposure time overall, with the highest proportion of exposure time on dipeptidyl peptidase 4 inhibitors, as well as metformin, insulin, and others.

The analysis showed that patients taking an SGLT2 inhibitor had a lower risk of heart failure (HR, 0.59; 95% CI, 0.47-0.74; P < .001) all-cause mortality (HR, 0.41; 95% CI, 0.31-0.54; P < .001), either all-cause mortality or heart failure (HR, 0.55; 95% CI, 0.47-0.63; P < .001), modified major adverse cardiovascular events (HR, 0.62; 95% CI, 0.52-0.74; P < .001), and chronic kidney disease (HR, 0.66; 95% CI, 0.54-0.80; P < .001).

The authors wrote that their study should provide confidence in the benefits of SGLT2 inhibitors, given the large study population size.

“Moreover, our study involves real-world data from a South European region where the prevalence of [cardiovascular] risk factors and [cardiovascular] disease in patients with [type 2 diabetes] is expected to be different from that in Northern Europe or the US,” they wrote.

The fact that the results held up despite a lower-risk population suggests the benefits of SGLT2 inhibitors are not an anomaly, nor are they limited to certain high-risk populations.

However, the authors also noted several limitations, such as the relatively small follow-up time, the reliance on potentially incomplete electronic health records, and limited access to socioeconomic data.

Still, the investigators said these new data add to the case for using SGLT2 inhibitors to protect patients with type 2 diabetes.

“These results expand previous observational studies supporting the use of SGLT2 [inhibitors] in patients with a broad [cardiovascular] risk profile in real-world clinical practice,” they concluded.


Real J, Vlacho B, Ortega E, et al. Cardiovascular and mortality benefits of sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus: CVD-Real Catalonia. Cardiovasc Diabetol. 2021;20(1):139. doi:10.1186/s12933-021-01323-5

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