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
The incidence of MACE-3 was significantly reduced among patients treated with semaglutide (P = .02) after median followup of 2.1 years. The expanded composite outcome (death from CV causes, nonfatal MI, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina or HF), also showed a significant reduction with semaglutide (P = .002), compared with placebo. There was no difference in the overall hospitalization rate or rate of death from any cause.
EXSCEL. The Exenatide Study of Cardiovascular Event Lowering trial (EXSCEL)17,18 was a phase III/IV, double-blind, pragmatic placebo-controlled study of 14,752 patients at any level of CV risk, for a median 3.2 years. The study population was intentionally more diverse than in earlier GLP-1 receptor agonist studies. The researchers hypothesized that patients at increased risk of MACE would experience a comparatively greater relative treatment benefit with exenatide than those at lower risk. That did not prove to be the case.
EXSCEL did confirm noninferiority compared with placebo (P < .001), but once-weekly exenatide resulted in a nonsignificant reduction in major adverse CV events, and a trend for RRR in all-cause mortality (RRR = 14%; ARR = 1% [P = .06]).
HARMONY OUTCOMES. The Albiglutide and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Cardiovascular Disease study (HARMONY OUTCOMES)19 was a double-blind, randomized, placebocontrolled trial conducted at 610 sites across 28 countries. The study investigated albiglutide, 30 to 50 mg once weekly, compared with placebo. It included 9463 patients ages ≥ 40 years with T2D who had an HbA1c > 7% (median value, 8.7%) and established CV disease. Patients were evaluated for a median 1.6 years.
Albiglutide reduced the risk of CV causes of death, nonfatal MI, and nonfatal stroke by an RRR of 22%, (ARR, 2%) (noninferiority, P < .0001; superiority, P < .0006).
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