What are the cardiac side effects of Ozempic (semaglutide)?

Cardiac Side Effects of Ozempic (Semaglutide)

Ozempic (semaglutide) can increase heart rate by 2-3 beats per minute but has demonstrated cardiovascular benefits in clinical trials, with significant reductions in major adverse cardiovascular events in patients with established cardiovascular disease. 1, 2

Primary Cardiovascular Effects

• Heart Rate Increase: FDA labeling indicates that Ozempic 0.5 mg and 1 mg doses result in a mean increase in heart rate of 2-3 beats per minute 2

• Cardiovascular Benefits:

  • Semaglutide has been shown to reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes 1
  • In the SUSTAIN-6 trial, semaglutide demonstrated a 26% reduction in the primary composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke (HR 0.74; 95% CI 0.58-0.95; P<0.001) 1
  • The recent SELECT trial showed that in patients with obesity without diabetes, semaglutide 2.4 mg reduced cardiovascular events by 20% compared to placebo (HR 0.80; 95% CI 0.72-0.90; P<0.001) 3

Potential Cardiovascular Adverse Effects

1. Heart Rate Increase:

   • Mean increase of 2-3 beats per minute 2
   • This is generally considered clinically insignificant for most patients

2. Hypoglycemia Risk:

   • Increased risk when combined with insulin or sulfonylureas 2
   • Severe hypoglycemia occurred in 0.8% and 1.2% of patients when Ozempic 0.5 mg and 1 mg was co-administered with a sulfonylurea 2
   • Hypoglycemia can indirectly affect cardiovascular function

3. Diabetic Retinopathy Complications:

   • Increased risk noted with semaglutide, predominantly in patients with prior history of proliferative retinopathy 1
   • This is hypothesized to be due to rapid and sustained reductions in blood glucose 1

Monitoring Recommendations

• Heart Rate: Monitor heart rate at baseline and periodically during treatment 2

• Blood Glucose: More frequent monitoring when used with insulin secretagogues or insulin to minimize hypoglycemia risk 1

• Retinal Examination: Patients should have a recent eye examination prior to semaglutide initiation, especially those with history of retinopathy 1

• Renal Function: Monitor renal function, especially in patients with nausea and possible dehydration 1

Special Populations and Contraindications

• Contraindications:

  • Personal or family history of medullary thyroid carcinoma 1, 4
  • Multiple endocrine neoplasia syndrome type 2 (MEN2) 1, 4
  • History of serious hypersensitivity reaction to semaglutide 1

• Use with Caution:

  • Patients with history of pancreatitis 1
  • Patients with severe renal impairment or end-stage renal disease 1
  • Patients with clinically significant gastroparesis 1

Clinical Implications

• Cardiovascular Risk Reduction: The American College of Cardiology recognizes GLP-1 receptor agonists like semaglutide as effective agents for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease 1

• Dose Adjustments: When initiating semaglutide, dose adjustments of other agents may be needed to minimize hypoglycemia risk for patients at or near glycemic targets 1

• Gastrointestinal Side Effects: Transient nausea and vomiting are common but can be minimized by starting with the lowest dose and titrating gradually 1, 2

• Medication Interactions: Should not be co-administered with DPP4 inhibitors as they both work through GLP-1 signaling 1

The cardiovascular profile of semaglutide is generally favorable, with demonstrated benefits in reducing cardiovascular events outweighing the minor increase in heart rate for most patients with established cardiovascular disease or high cardiovascular risk.