CVD-REAL 2 data support cardiovascular benefits of SGLT2 inhibitors
medwireNews: The latest CVD-REAL 2 data confirm clinical trial findings by showing that sodium-glucose co-transporter (SGLT)2 inhibitors significantly lower cardiovascular disease risk in people with type 2 diabetes, this time in comparison with dipeptidyl peptidase (DPP)-4 inhibitors.
“Despite variable patient characteristics, health-care settings, practice patterns, and specific SGLT2 inhibitor drugs used, the directions of associations were consistent across countries and regions and across the subgroups with or without previous cardiovascular disease,” report Shun Kohsaka (Keio University School of Medicine, Tokyo, Japan) and co-investigators in The Lancet Diabetes & Endocrinology.
The analysis included clinical practice data for nearly 400,000 propensity score matched patients with type 2 diabetes who initiated treatment with an SGLT2 or DPP-4 inhibitor (n=193,124 per group) between December 2012 and May 2016.
The individuals were from 13 countries in the Asia-Pacific, Middle East, European, and North American regions and had a mean age of 58 years. Around 30% had cardiovascular disease at baseline and 44% were women.
The most commonly used SGLT2 inhibitor was dapagliflozin, contributing 60% of total exposure time in this class, followed by canagliflozin (23%), and empagliflozin (13%). Sitagliptin was the most common DPP-4 inhibitor (49% of total exposure time), followed by linagliptin (20%), and saxagliptin (11%).
During a median 1.2 years of follow-up, the researchers found that individuals in the SGLT2 inhibitor group had a significant 31% lower risk for hospitalization for heart failure than those in the DPP-4 inhibitor group, with incidence rates of 0.79 versus 1.07 cases per 100 person–years.
The risk for all-cause mortality was a significant 41% lower with SGLT-2 inhibitors (0.84 vs 1.37 deaths per 100 person–years), while the composite risk for both of these outcomes was a significant 76% lower with SGLT-2 inhibitor use (1.56 vs 2.27 events per 100 person–years).
The risks for stroke and myocardial infarction were also significantly lower with SGLT2 inhibitors than with DPP-4 inhibitors but to a lesser degree, at 15% and 12%, respectively.
Kohsaka and co-authors believe that their findings “are especially important, because […] a much larger proportion of patients were initiated on DPP-4 inhibitors than SGLT2 inhibitors across most geographical regions.”
Indeed, of the 2,413,198 individuals initially eligible for inclusion, just 9.6% were new users of SGLT2 inhibitors, with the remainder starting DPP-4 inhibitors.
And the investigators conclude that their study provides “further support for the cardiovascular benefits associated with use of SGLT2 inhibitors in patients with type 2 diabetes.”
In an accompanying comment, Hertzel Gerstein, from McMaster University in Hamilton, Ontario, Canada, said that the study “reassures clinicians and the people who pay for health care that [previous] clinical trials, which were done in a highly selected population, are generalisable to the so-called average patient with type 2 diabetes.”
He concludes that “clinicians can be confident that prescribing an SGLT2 inhibitor will, on average, provide more cardiovascular benefits than prescribing a DPP-4 inhibitor. Similar epidemiological analyses of renal outcomes, which have also shown to be reduced in large outcomes trials, will extend this confidence even further.”
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