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
Cardiovascular outcomes trials: SGLT-2 inhibitors
EMPA-REG OUTCOME. The Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes trial (EMPA-REG OUTCOME) was also a landmark study because it was the first dedicated CVOT to show that an antihyperglycemic agent 1) decreased CV mortality and all-cause mortality, and 2) reduced HHF in patients with T2D and established CV disease.22 In this trial, 7020 patients with T2D who were at high risk of CV events were randomized and treated with empagliflozin, 10 or 25 mg, or placebo, in addition to standard care, and were followed for a median 2.6 years.
Compared with placebo, empagliflozin resulted in an RRR of 14% (ARR, 1.6%) in the primary endpoint of CV death, nonfatal MI, and stroke, confirming study drug superiority (P = .04). When compared with placebo, the empagliflozin group had an RRR of 38% in CV mortality, (ARR < 2.2%) (P < .001); an RRR of 35% in HHF (ARR, 1.4%) (P = .002); and an RRR of 32% (ARR, 2.6%) in death from any cause (P < .001).
CANVAS. The Canagliflozin Cardiovascular Assessment Study (CANVAS) integrated 2 multicenter, placebo-controlled, randomized trials with 10,142 participants and a mean follow-up of 3.6 years.23 Patients were randomized to receive canagliflozin (100-300 mg/d) or placebo. Approximately two-thirds of patients had a history of CV disease (therefore representing secondary prevention); one-third had CV risk factors only (primary prevention).
In CANVAS, patients receiving canagliflozin had a risk reduction in MACE-3, establishing superiority compared with placebo (P < .001). There was also a significant reduction in progression of albuminuria (P < .05). Superiority was not shown for the secondary outcome of death from any cause. Canagliflozin had no effect on the primary endpoint (MACE-3) in the subgroup of participants who did not have a history of CV disease. Similar to what was found with empagliflozin in EMPA-REG OUTCOME, CANVAS participants had a reduced risk of HHF.
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