What are the considerations for using Ozempic (semaglutide) in patients with heart problems?

Ozempic (Semaglutide) and Heart Problems

Semaglutide is strongly recommended for patients with type 2 diabetes and cardiovascular disease or heart failure, as it significantly reduces major cardiovascular events, heart failure hospitalizations, and cardiovascular death. 1

Cardiovascular Benefits

For Patients with Established Cardiovascular Disease

• Semaglutide reduces major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal myocardial infarction, and stroke by approximately 26% in patients with type 2 diabetes and established cardiovascular disease 1

• In patients without diabetes but with overweight/obesity and cardiovascular disease, semaglutide 2.4 mg weekly reduced the primary cardiovascular endpoint (cardiovascular death, non-fatal MI, or stroke) from 8.0% to 6.5% (hazard ratio 0.80) over a mean follow-up of 39.8 months 2

• The 2024 ESC guidelines recommend that semaglutide should be considered in chronic coronary syndrome patients without diabetes but with overweight or obesity (BMI >27 kg/m²) to reduce cardiovascular mortality, MI, or stroke 1

For Patients with Heart Failure

• Semaglutide substantially reduces heart failure outcomes across the entire spectrum of heart failure, including both preserved and reduced ejection fraction 3, 4

• In the pooled analysis of SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM trials, semaglutide reduced the combined endpoint of cardiovascular death or worsening heart failure events by 31% (HR 0.69) in patients with heart failure with preserved ejection fraction (HFpEF) 3

• Worsening heart failure events alone were reduced by 41% (HR 0.59) with semaglutide treatment 3

• In patients with atherosclerotic cardiovascular disease and heart failure at baseline, semaglutide reduced MACE by 28% (HR 0.72) and the composite heart failure endpoint by 21% (HR 0.79) 4

• Benefits were consistent regardless of baseline heart failure status, ejection fraction subtype (preserved vs. reduced), or NYHA functional class 3, 4

For Patients with Chronic Kidney Disease

• In the FLOW trial of patients with type 2 diabetes and chronic kidney disease, semaglutide reduced the composite of heart failure events or cardiovascular death by 27% (HR 0.73) over a median 3.4 years 5

• Cardiovascular death alone was reduced by 29% (HR 0.71) in this high-risk population 5

• These benefits occurred regardless of baseline heart failure status, with similar risk reductions in those with and without pre-existing heart failure 5

Guideline Recommendations

European Society of Cardiology (2019)

• Liraglutide, semaglutide, or dulaglutide are recommended in patients with type 2 diabetes and cardiovascular disease, or at very high/high cardiovascular risk, to reduce cardiovascular events 1

• Liraglutide is specifically recommended to reduce the risk of death in this population 1

American Diabetes Association (2023)

• GLP-1 receptor agonists including semaglutide showed no increased risk of heart failure hospitalization in cardiovascular outcomes trials, unlike some other diabetes medications 1

• Semaglutide improved outcomes in both heart failure with reduced ejection fraction and preserved ejection fraction groups in meta-analyses 1

American College of Cardiology (2020)

• Semaglutide should be considered at the time of diagnosis of clinical atherosclerotic cardiovascular disease, diabetic kidney disease, or heart failure in patients with type 2 diabetes 1

• Consider initiation at hospital discharge after admission for an atherosclerotic cardiovascular disease or heart failure event, with close outpatient follow-up 1

Safety Considerations in Heart Disease

Cardiovascular-Specific Safety

• Semaglutide can cause modest increases in heart rate, which should be monitored, particularly in patients with pre-existing cardiac arrhythmias 1

• No increased risk of heart failure hospitalization has been identified with semaglutide, unlike saxagliptin (a DPP-4 inhibitor) which increased heart failure hospitalizations 1

• Serious adverse events were less frequent with semaglutide versus placebo in cardiovascular outcomes trials, regardless of heart failure subtype 4

Important Contraindications and Warnings

• Do not use in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 6

• Risk of dehydration and renal impairment from gastrointestinal side effects requires monitoring, particularly important in heart failure patients on diuretics 6

• Diabetic retinopathy complications were increased with semaglutide in SUSTAIN-6, hypothesized to relate to rapid glucose reduction; patients should undergo eye examinations before starting therapy 1

Dosing Considerations

• For cardiovascular risk reduction in type 2 diabetes: Start at 0.25 mg weekly, escalate to 0.5 mg after 4 weeks, then to 1 mg weekly 6

• For obesity and cardiovascular disease without diabetes: Escalate to 2.4 mg weekly over 16 weeks 2, 4

• Dose adjustments are not required for renal impairment, though caution is advised in severe renal disease 1

Clinical Algorithm for Initiation

Start semaglutide in the following scenarios:

1. Type 2 diabetes with established cardiovascular disease (prior MI, stroke, or revascularization) 1

2. Type 2 diabetes with heart failure (any ejection fraction) 1, 3, 4

3. Type 2 diabetes with chronic kidney disease (particularly with albuminuria) 1, 5

4. Overweight/obesity (BMI >27 kg/m²) with cardiovascular disease, even without diabetes 1, 2

5. At hospital discharge after cardiovascular or heart failure event in patients with type 2 diabetes 1

Monitor for:

• Gastrointestinal symptoms (nausea, vomiting) - most common, usually transient 1, 6
• Heart rate changes 1
• Hypoglycemia if on insulin or sulfonylureas (reduce doses of these agents) 1, 6
• Renal function, especially if dehydration occurs 6