A 58-year-old woman with type 2 diabetes mellitus (HbA1c 8.1% on metformin and glimepiride), BMI 34 kg/m², hypertension, and a history of non-ST-elevation myocardial infarction 14 months ago asks whether any glucose-lowering agent has been shown to reduce major adverse cardiovascular events in a dedicated cardiovascular outcome trial in patients like her. Based on the LEADER trial, which recommendation is evidence-based?

• A Add sitagliptin; the TECOS trial demonstrated reduced three-point MACE in high-risk type 2 diabetes.
• B Intensify metformin alone; no GLP-1 receptor agonist has demonstrated cardiovascular event reduction in a dedicated trial.
• C Add canagliflozin; the CANVAS program is the only SGLT2 inhibitor trial that showed cardiovascular benefit.
• D Add liraglutide; the LEADER trial showed a significant reduction in the three-point MACE composite in patients with prior cardiovascular disease or high cardiovascular risk. ✓

Explanation

The LEADER trial (N Engl J Med 2016) randomized 9340 patients with type 2 diabetes and high cardiovascular risk to liraglutide or placebo and demonstrated a 13% relative reduction in the three-point MACE composite (CV death, nonfatal MI, nonfatal stroke). Option A is incorrect because TECOS showed sitagliptin was non-inferior, not superior. Option C is wrong because both CANVAS and EMPA-REG OUTCOME demonstrated benefit.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.