Dulaglutide in Type 2 Diabetes and Heart Failure
Dulaglutide is recommended for patients with type 2 diabetes and heart failure as it reduces cardiovascular events without increasing heart failure risk, making it a beneficial treatment option for this population. 1, 2
Cardiovascular Benefits of Dulaglutide
Dulaglutide has demonstrated significant cardiovascular benefits in patients with type 2 diabetes:
- Reduces major adverse cardiovascular events (MACE) with a hazard ratio of 0.88 (95% CI 0.79-0.99) 3
- Benefits observed in patients with established cardiovascular disease and those with multiple cardiovascular risk factors 4
- The European Society of Cardiology (ESC) guidelines specifically recommend dulaglutide in patients with T2DM and cardiovascular disease, or those at very high/high cardiovascular risk, to reduce cardiovascular events 1
Heart Failure Considerations
When considering dulaglutide specifically for patients with heart failure:
- Dulaglutide does not increase the risk of heart failure events in patients with type 2 diabetes, regardless of baseline heart failure status 2
- In the REWIND trial, dulaglutide showed no significant difference in heart failure events compared to placebo (HR 0.93,95% CI 0.77-1.12) over a median follow-up of 5.4 years 2
- Combined cardiovascular death and heart failure events were marginally reduced with dulaglutide compared to placebo (HR 0.88,95% CI 0.78-1.00; p=0.050) 2
Advantages Over Other Antihyperglycemic Agents
Dulaglutide offers several advantages for patients with type 2 diabetes and heart failure:
- Unlike thiazolidinediones, which have a strong association with increased heart failure risk, dulaglutide does not worsen heart failure 1
- Unlike saxagliptin (a DPP-4 inhibitor), which is not recommended in patients with T2DM and high risk of heart failure, dulaglutide has neutral effects on heart failure 1
- Once-weekly administration improves adherence compared to daily medications 5
Treatment Algorithm for T2DM with Heart Failure
First-line therapy: SGLT2 inhibitors (empagliflozin, canagliflozin, or dapagliflozin) are recommended to lower risk of heart failure hospitalization 1
Second-line therapy:
- If patient has established cardiovascular disease or is at high cardiovascular risk: Add dulaglutide
- If patient has heart failure with reduced ejection fraction: Consider metformin if eGFR >30 mL/min/1.73 m² 1
Avoid in heart failure patients:
Dosing and Monitoring
- Initial dose: 0.75 mg subcutaneously once weekly 4
- Maintenance dose: 1.5 mg once weekly for additional glycemic control 4
- No dose adjustment required in patients with renal insufficiency 4
Potential Side Effects and Cautions
- Most common adverse events are gastrointestinal (nausea, vomiting, diarrhea) 4, 3
- Low incidence of hypoglycemia when used alone or with therapies that do not stimulate insulin secretion 4
- Use with caution in patients with history of proliferative retinopathy 1
- Avoid in patients with history of medullary thyroid cancer or multiple endocrine neoplasia type 2 1, 4
Total Cardiovascular Burden Reduction
Beyond the primary cardiovascular outcomes, dulaglutide also reduces the total burden of cardiovascular events:
- Total MACE or non-cardiovascular deaths were reduced with dulaglutide (35.8 vs 40.3 per 1000 person-years; absolute reduction = 4.5 per 1000 person-years) 6
- Total expanded MACE or non-cardiovascular deaths were also reduced (67.1 vs 74.7 per 1000 person-years; absolute reduction = 7.6 per 1000 person-years) 6
In summary, dulaglutide is an effective treatment option for patients with type 2 diabetes and heart failure, offering cardiovascular benefits without increasing heart failure risk. It should be considered as part of a comprehensive treatment approach, particularly in patients with established cardiovascular disease or multiple cardiovascular risk factors.