At the 80th American Diabetes Association (ADA) scientific conference held this month, an exploratory analysis of DAPA-HF from the AstraZeneca SGLT2 inhibitor Farxiga (dapagliflozin) dapagliflozin heart failure study showed that the drug showed Signs to prevent type 2 diabetes: Farxiga reduces the risk of new type 2 diabetes by almost a third compared to placebo.

Farxiga can effectively treat type 2 diabetes. The drug was also approved in May this year as a new indication for adult patients with heart failure with reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular death and heart failure hospitalization, whether or not There is type 2 diabetes. The new findings announced this time represent an emerging market for SGLT2 inhibitors and are believed to help drive sales of new uses for Farxiga. The data may also prompt endocrinologists to consider using these drugs as early as possible in the treatment of diabetes.

The diabetes prevention analysis has been pre-specified in the DAPA-HF study protocol, but this new discovery is only considered exploratory. DAPA-HF is a heart failure trial and enrolled 4774 patients with HFrEF. About half of the subjects entered the study without diabetes. These patients were equally divided into the Farxiga group and the placebo group. Among these patients without diabetes, 4.9% of the 1298 patients in the Farxiga group developed type 2 diabetes within 18 months, and 7.1% of the 1307 patients in the placebo group, which is equivalent to the risk of new type 2 diabetes A 32% reduction (p=0.019).

Dr. Silvio Inzucchi, principal investigator of DAPA-HF and professor of medicine at Yale University School of Medicine, pointed out that this analysis has some limitations, including shorter follow-up time, and that the study is not a pure diabetes prevention trial. However, in cohort patients without diabetes at baseline, Farxiga had minimal effect on HbA1c or body weight. This indicates that the inhibitory effect of SGLT2 may not only prevent the development of diabetes, this problem has been raised after the diabetes prevention research of other hypoglycemic drugs.

Metformin has long been a universal diabetes drug and is considered to have the most evidence to support its application in prevention. This is mainly based on a 20-year trial called Diabetes Prevention Programme, which found that metformin Reduced the risk of diabetes in patients with impaired glucose tolerance by 31%.

Inzucchi pointed out that the 32% reduction in the risk found in DAPA-HF “prompts that in the HFrEF population, perhaps these guidelines should be considered to include the possibility of SGLT2 inhibitors as a baseline therapy, even before the use of metformin.

When asked whether endocrinologists should reconsider metformin as the first drug for diabetes, Inzucchi said: “Does metformin use more than SGLT2 outside the diabetes guidelines, especially in patients with cardiovascular disease? Obviously No, the use of metformin is largely based on a tradition. Many patients need at least 2 drugs, why not use SGLT2 inhibitors while taking metformin?”

Of course, this is pleasant information for all SGLT2 inhibitor manufacturers. In addition to AstraZeneca, it also includes Eli Lilly and Boehringer Ingelheim (Jardiance) and Johnson & Johnson (Invokana), these pharmaceutical companies have invested in huge clinical projects, the purpose is to expand the application of these drugs to the field of heart disease and kidney disease . Moreover, with more and more evidence of the broad protective effect of SGLT2 inhibitors, sales forecasts for these drugs have also soared.

At present, the mechanism behind the broad benefits of SGLT2 inhibitors is not fully understood, although most people agree that many different pathways may work.

AstraZeneca’s Senior Vice President of Cardiovascular, Kidney and Metabolism Joris Silon speculates that SGLT2 inhibitors will promote the loss of urine salts and glucose, and a series of physiological adaptations to this process may provide preventive benefits.

Joris Silon also said that AstraZeneca is unlikely to conduct any special diabetes prevention research on Farxiga, nor is it likely to seek indications for diabetes prevention.

However, real-world evidence hopes to add to this discovery. The DAPA-CKD study tested Farxiga in patients with chronic kidney disease (CKD), and the study also included an exploratory diabetes prevention analysis. Due to the significant effect, the study was stopped early in March this year.

Reducing the risk of end-stage renal disease or death in all CDK patients was a huge victory, just like the DAPA-HF study’s goal of reducing all patients’ heart failure hospitalization rates and mortality rates. As SGLT2 inhibitors show benefits in more and more patients, the discovery of diabetes prevention signals will undoubtedly be the icing on the cake for such drugs.