What is the recommended approach for initiating GLP-1 (Glucagon-like peptide-1) and SGLT2 (Sodium-glucose cotransporter 2) inhibitors in a patient 2 weeks after Non-ST-Elevation Myocardial Infarction (NSTEMI) and Coronary Artery Bypass Grafting (CABG) x 3?

Initiating GLP-1 and SGLT2 Inhibitors After NSTEMI and CABG

Do not initiate SGLT2 inhibitors at 2 weeks post-CABG due to significant risk of euglycemic diabetic ketoacidosis (EDKA) that can precipitate acute coronary syndrome and cardiac arrest; GLP-1 agonists can be safely initiated once the patient is hemodynamically stable, eating normally, and has no ongoing surgical complications.

SGLT2 Inhibitors: High-Risk Period Post-CABG

Critical Safety Concern

• SGLT2 inhibitors should be discontinued at least 3 days before major cardiac surgery and should not be restarted in the immediate postoperative period due to the risk of EDKA, which can trigger myocardial ischemia, arrhythmias, and cardiac arrest even with normal blood glucose levels 1.

• A documented case demonstrates that EDKA occurring on postoperative day 5 after CABG precipitated critical stenosis of a bypass graft, requiring emergent intervention—illustrating that metabolic stress from EDKA can act as a "cardiac stress test" triggering acute coronary events 1.

When to Consider SGLT2 Inhibitors

• Wait at least 4-6 weeks post-CABG before initiating SGLT2 inhibitors, ensuring the patient is:

  • Hemodynamically stable with no signs of heart failure decompensation
  • Eating a normal diet (not NPO or on restricted intake)
  • Free from surgical complications or infections
  • Off intravenous fluids and insulin drips 1

• Once stable, SGLT2 inhibitors are strongly indicated for patients with heart failure (regardless of ejection fraction), chronic kidney disease with albuminuria, or type 2 diabetes with established atherosclerotic cardiovascular disease to reduce cardiovascular mortality, heart failure hospitalization, and renal decline 2.

GLP-1 Receptor Agonists: Earlier Initiation Possible

Timing for Initiation

• GLP-1 agonists can be initiated within 1-2 weeks post-CABG once the patient meets these criteria:
  • Tolerating oral intake without nausea or vomiting
  • Hemodynamically stable
  • No active surgical site complications
  • Adequate renal function (most GLP-1 agonists require eGFR >30 mL/min) 2

Cardiovascular Benefits

• GLP-1 receptor agonists reduce major adverse cardiovascular events, cardiovascular mortality, and nonfatal stroke in patients with type 2 diabetes and established atherosclerotic cardiovascular disease 3, 2.

• These agents provide weight reduction, blood pressure lowering, and low hypoglycemia risk—all beneficial in the post-CABG recovery period 3.

Standard Post-CABG Cardiac Medications (Priority)

Antiplatelet Therapy

• Continue aspirin 81 mg daily indefinitely without interruption, as it reduces perioperative myocardial infarction, acute renal injury, and mortality 4.

• Resume P2Y12 inhibitor (clopidogrel 75 mg daily) within 12-24 hours post-CABG once hemostasis is achieved, unless contraindicated by bleeding 4.

• Continue dual antiplatelet therapy for at least 12 months post-CABG in patients who had recent NSTEMI 5.

Other Guideline-Directed Medical Therapy

• Beta-blockers should be initiated within a few days if not started acutely and continued indefinitely for all post-NSTEMI patients unless contraindicated 5.

• ACE inhibitors or ARBs should be given and continued indefinitely for patients with heart failure, LVEF <40%, hypertension, or diabetes mellitus 5.

• High-intensity statin therapy should never be discontinued perioperatively and must be continued throughout the post-CABG period 4.

Practical Algorithm for GLP-1/SGLT2 Initiation

Week 2 Post-CABG (Current Timepoint)

1. Ensure standard post-CABG medications are optimized: aspirin, P2Y12 inhibitor, beta-blocker, ACE inhibitor/ARB, high-intensity statin 5, 4
2. Consider initiating GLP-1 agonist if patient has type 2 diabetes, is eating normally, and has no nausea/vomiting 2
3. Do NOT initiate SGLT2 inhibitor at this timepoint 1

Week 4-6 Post-CABG

1. Reassess for SGLT2 inhibitor initiation if patient is:

   • Fully recovered from surgery
   • On stable oral diet
   • No active complications
   • Has indication (heart failure, CKD with albuminuria, or type 2 diabetes with ASCVD) 2

2. Continue GLP-1 agonist if already started and well-tolerated 2

Common Pitfalls to Avoid

• Never start SGLT2 inhibitors in the early post-CABG period (first 3-4 weeks), as the risk of EDKA with catastrophic cardiac consequences outweighs any potential benefit 1.

• Do not delay standard guideline-directed medical therapy (aspirin, P2Y12 inhibitor, beta-blocker, ACE inhibitor, statin) while considering newer agents—these remain the foundation of post-NSTEMI/CABG care 5, 4.

• Avoid initiating GLP-1 agonists in patients with significant nausea, vomiting, or gastroparesis, as these agents can worsen gastrointestinal symptoms and compromise nutritional recovery 2.

• Monitor for signs of EDKA if SGLT2 inhibitor is eventually started: unexplained metabolic acidosis with high anion gap, even with normal glucose levels, especially during periods of reduced oral intake or intercurrent illness 1.