We know that several medications for type 2 diabetes reduce the risk of cardiovascular events in people with type 2 diabetes and established cardiovascular disease (this is called ‘secondary prevention’).  However, none of these medications have been shown to reduce cardiovascular events in people without pre existing cardiovascular disease (called ‘primary prevention’).


The greatly anticipated DECLARE trial of dapagliflozin, an SGLT2 inhibitor, was published just days ago in the New England Journal of Medicine.  DECLARE is the largest cardiovascular outcome trial to date, with over 17,000 patients enrolled, and randomized patients to receive either dapagliflozin (trade name Forxiga, or Farxiga in USA) 10mg vs placebo.  This study is unique compared to other published studies in that the majority of the patients in the study (59%) did not have any history of cardiovascular disease.  Other published studies included mostly patients with established disease, so until now, we did not have a lot of data in people without cardiovascular disease.  There were two primary endpoints to the DECLARE trial: the standard ‘MACE’ cardiovascular safety outcome, which is a combination of cardiovascular death + non fatal heart attack + non fatal stroke; and a composite of cardiovascular death and hospitalization for heart failure.


After a median of 4.2 years, this study found that dapagliflozin reduced the primary composite outcome of cardiovascular death and hospitalization for heart failure, with this result being driven by an impressive 27% reduction in hospitalization for heart failure (dapagliflozin did not prevent death).  Importantly, hospitalization for heart failure was reduced in people with or without a history of cardiovascular disease, and in people with or without a prior history of heart failure.


Dapagliflozin did not prevent cardiovascular events (MACE), which is different from other medications in this class [empagliflozin (Jardiance) and canagliflozin (Invokana)], which have been shown to reduce cardiovascular events in people with a history of cardiovascular disease. This may be because people in the DECLARE study were healthier from a kidney perspective, and/or because the overall cardiovascular event rate in DECLARE was lower than in the other two studies (based on comparison of event rates in the placebo groups).


BOTTOM LINE: This study shows that dapagliflozin prevents heart failure in a broad range of people with type 2 diabetes (with or without cardiovascular disease, and with or without a past history of heart failure), which is very important – heart failure is common in people with diabetes, often undiagnosed, and can be fatal.  As discussed in a meta analysis of the cardiovascular outcome trials of these three medications published simultaneously, this group of medications as a whole seems to reduce heart failure risk as well as protect kidneys in a broad range of patients with type 2 diabetes, while the benefit to reduce cardiovascular events with this class of medication seems to be limited to those with pre existing cardiovascular disease.


Disclaimer:  I receive honoraria as a continuing medical education speaker and consultant from the makers of dapagliflozin (Astra Zeneca), empagliflozin (Boehringer Ingelheim/Eli Lilly), and canagliflozin (Janssen). I have been involved as an investigator in clinical trials of SGLT2 inhibitors.


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