What are the considerations for using Trulicity (dulaglutide) in a patient with Chronic Kidney Disease (CKD) stage 4 and Impaired renal function?

From the Guidelines

Trulicity (dulaglutide) can be used in patients with stage 4 CKD and impaired renal function without dose adjustment, as it is primarily metabolized through protein degradation into its component amino acids, rather than being eliminated through renal excretion, making it safe in advanced kidney disease 1.

Key Considerations

• No dose modification is required regardless of renal function, including for patients with eGFR as low as 15 mL/min/1.73m², according to the latest guidelines 1.
• Patients with severe renal impairment should be monitored closely for potential adverse effects such as nausea, vomiting, and diarrhea, which may lead to dehydration and worsen kidney function 1.
• Trulicity should be initiated at the standard dose of 0.75 mg subcutaneously once weekly, with potential titration to 1.5 mg weekly after four weeks if needed and tolerated 1.

Monitoring and Precautions

• It's essential to maintain adequate hydration while using this medication and to monitor renal function periodically 1.
• Caution should be exercised in patients with a history of diabetic ketoacidosis, pancreatitis, or severe gastrointestinal disease, as Trulicity may exacerbate these conditions 1.

Benefits and Recommendations

• The use of GLP-1 receptor agonists, such as Trulicity, is recommended for patients with CKD to provide both kidney and cardiovascular protective benefits, according to recent updates to clinical guidelines 1.
• An integrated approach to patient care with a multidisciplinary focus can help achieve the necessary shift in clinical care of patients with CKD and diabetes 1.

From the FDA Drug Label

In a clinical pharmacology study in patients with renal impairment, including end-stage renal disease (ESRD), no clinically relevant change in dulaglutide pharmacokinetics (PK) was observed. No dose adjustment is recommended in patients with renal impairment including end-stage renal disease (ESRD). Monitor renal function in patients with renal impairment reporting severe adverse gastrointestinal reactions. Use TRULICITY with caution in patients with ESRD [see Warning and Precautions (5.5), Clinical Pharmacology (12.3)].

Considerations for using Trulicity in a patient with CKD stage 4:

• No dose adjustment is recommended for patients with renal impairment, including those with CKD stage 4.
• Monitor renal function in patients with CKD stage 4 who report severe adverse gastrointestinal reactions.
• Use Trulicity with caution in patients with CKD stage 4, as there may be an increased risk of adverse gastrointestinal reactions.
• The pharmacokinetics of dulaglutide are not significantly affected by renal impairment, including CKD stage 4 2.

From the Research

Considerations for Using Trulicity (Dulaglutide) in Patients with CKD Stage 4

• Trulicity (dulaglutide) is a long-acting glucagon-like peptide-1 receptor agonist that can be used in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (CKD) 3.
• The AWARD-7 trial demonstrated that dulaglutide produced glycaemic control similar to that achieved with insulin glargine, with reduced decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes and moderate-to-severe CKD 3.
• Dulaglutide seems to be safe to use to achieve glycaemic control in patients with moderate-to-severe CKD, with lower rates of symptomatic hypoglycaemia compared to insulin glargine 3.
• The effects of dulaglutide on eGFR and urine albumin-to-creatinine ratio (UACR) were evaluated in several clinical trials, and the results suggest that dulaglutide does not affect eGFR and slightly decreases albuminuria 4.

Renal Function and Trulicity

• Renal function markers, such as serum creatinine and eGFR, are important considerations when using Trulicity in patients with CKD 5.
• The use of serum creatinine as the single marker for renal function may lead to unnecessary under-prescription of metformin, and eGFR should be used as a more accurate measure of renal function 5.
• Dulaglutide treatment did not affect eGFR in clinical trial participants with type 2 diabetes, and slightly decreased albuminuria 4.

Clinical Outcomes with Trulicity in CKD

• The AWARD-7 trial demonstrated that treatment with dulaglutide slowed decline in eGFR compared with insulin glargine in participants with diabetes and CKD 3.
• An exploratory analysis of the AWARD-7 trial found that patients treated with dulaglutide had a lower risk of ≥40% eGFR decline or end-stage kidney disease (ESKD) events compared to those treated with insulin glargine, particularly in the subset of patients with macroalbuminuria 6.
• Dulaglutide remains an important option in the management of type 2 diabetes, given its durable glycaemic efficacy, beneficial effects on body weight and major adverse cardiac events, low inherent risk of hypoglycaemia, and convenient once-weekly regimen 7.