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ORLANDO -- SGLT-2 inhibitors showed better protection against all-cause death and against heart events than DPP-4 inhibitors, according to real-world international data presented here.

In the CVD-REAL 2 study, initiation of treatment with an SGLT-2 inhibitor for type 2 diabetes showed a significantly lowered risk for stroke, heart attack, heart failure, and all-cause death compared with treatment with any DPP-4 inhibitor, reported Shun Kohsaka, MD, of Keio University School of Medicine in Tokyo, and colleagues:

• All-cause death: HR 0.61 (95% CI 0.54 to 0.69)
• Stroke: HR 0.84 (95% CI 0.76 to 0.93)
• Myocardial infarction: HR 0.90 (95% CI 081 to 0.99)
• Hospitalization for heart failure (HHF): HR 0.68 (95% CI 0.60 to 0.78)
• HHF and all-cause death: HR 0.67 (95% CI 0.60 to 0.74)

The international head-to-head comparison study found a lowered risk of all-cause death with SGLT-2 inhibitors in all 12 countries included in the analysis, they reported in a late-breaking abstract at the American Diabetes Association annual meeting.

For U.S. patients, risk of all-cause death was nearly half for those on a newly initiated SGLT-2 inhibitor compared to a DPP-4 inhibitor (HR 0.55, 95% CI 0.48 to 0.62, P<0.001).

"The main novel aspect of this study is that we compared SGLT-2 i head-to-head with DPP4-i, rather than all other glucose-lowering agents," said co-author Mikhail Kosiborod, MD, of Saint Luke's Mid American Heart Institute and University of Missouri in Kansas City, to 番茄社区app. Although he said the group wasn't particularly surprised by these findings, he underscored the study's importance since there was a lack of a large analysis comparing these two classes directly.

"The results of this study continue to highlight the value of large, well-conducted real world studies, such as CVD-REAL, in providing complementary, clinically useful information to the findings being learned from cardiovascular outcomes studies -- and continuing to inform clinical practice," he added.

The large analysis pooled data on over 350,000 new users of SGLT-2 inhibitors or DPP-4 inhibitors from 12 counties, representing North America, Europe, the Middle East, and Asia. The patients were selected from deidentified health records, and followed-up for an average of about 1.5 years.

The most common SGLT-2 inhibitor prescribed was dapagliflozin (Farxiga), representing over 60% of the exposure time to SGLT-2's, followed by canagliflozin (Invokana) comprising of 24% of exposure time to SGLT-2's. Other less commonly used SGLT-2's reported were empagliflozin (Jardiance, 12%), as well as ipragliflozin (Suglat, 3%), tofogliflozin (Deberza, <1%), and luseogliflozin (0.3%) seen in Asia.

Most of the exposure time to DPP-4 inhibitors included sitagliptin (Januvia, 50%), followed by linagliptin (Tradjenta, 19%), and saxagliptin (Onglyza, 10.4%).

Over the course of follow-up, there were more all-cause deaths among the overall group treated with a DPP-4 inhibitor (2,950 deaths, IR 1.33 per 100 person-years) versus the SGLT-2 group (1,818 deaths, IR 0.83 per 100 person-years), consistent across all 12 countries.

These results build upon the previous findings of the CVD-REAL Nordic study released in August 2017, which found SGLT-2s were associated with a lowered heart risk in just a Scandinavian population.

A current study limitation was the inability to assess and compare safety of the treatment classes.

Nonetheless, Kosiborod added that his group continues to incorporate more data from additional countries, and continues to accumulate more events with a longer duration of follow-up. "A number of additional analyses are being planned using the CVD-REAL platform in the near future, and we look forward to sharing the results at the upcoming scientific meetings," he stated.

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