From the Guidelines
GLP-1 receptor agonists can be used in patients with impaired renal function undergoing dialysis, with semaglutide and dulaglutide being preferred options due to their favorable cardiovascular and kidney disease outcomes, as evidenced by the 2022 consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) 1.
Key Considerations
- GLP-1 receptor agonists have been shown to reduce albuminuria and slow eGFR decline, and have demonstrated beneficial effects in reducing cardiovascular events, particularly among persons with prevalent atherosclerotic cardiovascular disease 1.
- Semaglutide and dulaglutide are preferred options due to their favorable cardiovascular and kidney disease outcomes, and do not require dose adjustment in dialysis patients.
- Start with lower doses: semaglutide 0.25mg weekly, increasing to 0.5mg after 4 weeks if tolerated; or dulaglutide 0.75mg weekly, potentially increasing to 1.5mg weekly.
- Monitor for gastrointestinal side effects (nausea, vomiting, diarrhea), which are common initially but often improve with time.
Benefits and Risks
- GLP-1 receptor agonists offer cardiovascular benefits and may aid in weight management, which is beneficial for many dialysis patients.
- They help control blood glucose by increasing insulin secretion in response to food, reducing glucagon, and slowing gastric emptying.
- Regular blood glucose monitoring is essential, especially when initiating therapy, as is coordination between nephrology and endocrinology teams to ensure optimal management.
Additional Guidance
- The 2021 KDIGO clinical practice guideline recommends a long-acting GLP-1 RA for patients with type 2 diabetes and CKD who have not achieved individualized glycemic targets despite use of metformin and SGLT2i, or who are unable to use those medications 1.
- GLP-1 RAs are preferred additional agents due to their demonstrated beneficial effects in reducing cardiovascular events and their potential to prevent macroalbuminuria or reduction in eGFR decline.
From the Research
Role of GLP-1 in Patients with Impaired Renal Function Undergoing Dialysis
- GLP-1 receptor agonists have been shown to be effective in improving glycemic control, lowering HbA1c, albuminuria, weight, and blood pressure control in patients with type 2 diabetes and impaired renal function 2.
- The use of GLP-1 receptor agonists in patients with advanced-stage chronic kidney disease (CKD) has been approved by the European Medicines Agency, with a minimal eGFR of 15 mL/min/1.73 m2 2.
- Studies have demonstrated that GLP-1 receptor agonists can be used in patients with CKD stages 1-5, with benefits including improved glycemic control, weight loss, and reduced cardiovascular risk 3, 4, 5.
- A review of 42 studies involving 48,148 participants with type 2 diabetes and CKD found that GLP-1 receptor agonists probably reduced the risk of all-cause death and major cardiovascular events, but may have little or no effect on cardiovascular death, kidney failure, and composite kidney outcomes 6.
- The effects of GLP-1 receptor agonists on patients with impaired renal function undergoing dialysis are not well-established, with only one study conducted in people on dialysis 6.
- GLP-1 receptor agonists may have benefits in preserving residual kidney function (RKF) and allowing patients to maintain a weekly hemodialysis session, potentially facilitating their inclusion in kidney transplant waiting lists 2.
Mechanisms of Action
- GLP-1 receptor agonists work by augmenting hyperglycemia-induced insulin secretion, suppressing glucagon secretion, decelerating gastric emptying, and reducing calorie intake and body weight 3, 4, 5.
- Long-acting GLP-1 receptor agonists have more profound effects on overnight and fasting plasma glucose and HbA1c, with additional benefits including weight reduction and no intrinsic risk of hypoglycemic episodes 3.
Clinical Implications
- GLP-1 receptor agonists are recommended as the preferred first injectable glucose-lowering therapy for type 2 diabetes, even before insulin treatment, due to their substantial clinical benefits and potential to help reduce disease burden 3, 5.
- The choice of a specific GLP-1 receptor agonist should be based on patient preferences, potential adverse effects, and cost, with consideration of the individual risk of ischemic or heart failure complications 3, 4.