Cardiovascular Outcome Trials in Diabetes – Summary Article

I just finished the following review article reviewing the major cardiovascular outcome RCT’s with antihyperglycemics in type 2 diabetes.  With the sheer number of published trials, it can be difficult for clinicians to keep current.  Although a long read, the article provides a great perspective from top diabetes KOL’s on the studies published to date.  It includes a great summary of the key information from the main trials.

Major take-homes from the article:

  • Most of the trials published to date have used a 3-point composite major adverse cardiac event (MACE) primary outcome (CV death, nonfatal MI, and nonfatal stroke).
  • Trials have shown that insulins glargine and degludec, sitagliptin, alogliptin, saxagliptin, lixisenatide, and once-weekly exenatide have neutral effects on MACE outcomes, thereby supporting the use of these drugs when needed to improve glycemic control with the goal of limiting microvascular complications without increasing CV risk.
  • The evidence for CV benefit from empagliflozin, canagliflozin, liraglutide, and possibly semaglutide versus placebo, supplemented by data from other studies, already has prompted reconsideration of treatment guidelines and is likely to alter clinical practice and reduce CV events and deaths among people similar to those enrolled in these trials.
  • The positive effect of the tested drugs on kidney disease, itself a CV risk factor. For example, empagliflozin (HR 0.61 [95% CI 0.53–0.70], P < 0.001), canagliflozin (HR 0.60 [95% CI, 0.47–0.77], P < 0.0001), liraglutide (HR 0.78 [95% CI 0.67–0.92], P = 0.003), and semaglutide (HR 0.64 [95% CI 0.46–0.88], P = 0.005) all reduced progression of renal disease more than would be expected from the improvements in glucose and blood pressure provided by these drugs.
  • Although it is inherently inappropriate to compare results among trials because they are conducted in different populations, with different protocols, and at different sites, the numbers needed to treat (NNTs) to prevent a MACE occurrence in EMPA-REG OUTCOME (63 over 3.1 years), LEADER (53 over 3.8 years), and SUSTAIN-6 (44 over 2 years) were similar to those observed for widely recommended therapies to prevent CVD such as lipid lowering with statins, antihypertensive therapy, and aspirin.
  • There was a call for more long-term safety and innovative trial design to help reflect the broader population of patients with type 2 diabetes.

Overall, a good read for clinicians involved in the management of type 2 diabetes.  The article also has three Canadian key opinion leaders as authors (Hertzel C. Gerstein, Bernard Zinman,Lawrence A. Leiter).  For clinicians wanting to read more, it can be downloaded free of charge at the following link:

 

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