How to use type 2 diabetes meds to lower CV disease risk
The challenge: Translate evidence from cardiovascular outcomes trials of newer antidiabetic agents into a targeted management strategy.
PRACTICE RECOMMENDATIONS
› Consider American Diabetes Association (ADA) guidance and prescribe a sodium–glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide- 1 (GLP-1) receptor agonist that has demonstrated cardiovascular (CV) disease benefit for your patients who have type 2 diabetes (T2D) and established atherosclerotic CV disease. A
› Consider ADA’s recommendation for preferred therapy and prescribe an SGLT-2 inhibitor for your patients with T2D who have atherosclerotic CV disease and are at high risk of heart failure or in whom heart failure coexists. C
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
LEADER. The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results trial (LEADER) evaluated long-term effects of liraglutide, compared to placebo, on CV events in patients with T2D.15 It was a multicenter, double-blind, placebocontrolled study that followed 9340 participants, most (81%) of whom had established CV disease, over 5 years. LEADER is considered a landmark study because it was the first large CVOT to show significant benefit for a GLP-1 receptor agonist.
Liraglutide demonstrated reductions in first occurrence of death from CV causes, nonfatal MI or nonfatal stroke, overall CV mortality, and all-cause mortality. The composite MACE-3 showed a relative risk reduction (RRR) of 13%, equivalent to an absolute risk reduction (ARR) of 1.9% (noninferiority, P < .001; superiority, P < .01). The RRR was 22% for death from CV causes, with an ARR of 1.3% (P = .007); the RRR for death from any cause was 15%, with an ARR of 1.4% (P = .02).
In addition, there was a lower rate of nephropathy (1.5 events for every 100 patient–years in the liraglutide group [P = .003], compared with 1.9 events every 100 patient–years in the placebo group).15
Results clearly demonstrated benefit. No significant difference was seen in the liraglutide rate of HHF, compared to the rate in the placebo group.
SUSTAIN-6. Evidence for the CV benefit of GLP-1 receptor agonists was also demonstrated in the phase 3 Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN-6).16 This was a study of 3297 patients with T2D at high risk of CV disease and with a mean hemoglobin A1c (HbA1c) value of 8.7%, 83% of whom had established CV disease. Patients were randomized to semaglutide or placebo. Note: SUSTAIN-6 was a noninferiority safety study; as such, it was not actually designed to assess or establish superiority.
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