What is the preferred treatment for type 2 diabetes with impaired renal function, Glucagon-like peptide-1 (GLP-1) receptor agonists or insulin therapy?

From the Guidelines

For type 2 diabetes patients with impaired renal function, GLP-1 receptor agonists are the preferred treatment over insulin therapy due to their ability to reduce albuminuria and slow eGFR decline, as well as their cardiovascular benefits. The American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) recommend the use of GLP-1 receptor agonists in patients with type 2 diabetes and chronic kidney disease (CKD) who have not achieved individualized glycemic targets despite use of metformin and SGLT2 inhibitors, or who are unable to use those medications 1. GLP-1 receptor agonists have been shown to reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes, and their benefits are similar in patients with and without previous cardiovascular or kidney disease 1.

Some of the key benefits of GLP-1 receptor agonists include:

• Reduction in albuminuria and slowing of eGFR decline
• Cardiovascular benefits, including reduction in MACE
• Weight loss and improved glycemic control
• Low risk of hypoglycemia when used alone

However, GLP-1 receptor agonists can cause gastrointestinal side effects, such as nausea and vomiting, which can be minimized by starting with a low dose and titrating up slowly 1. The choice of GLP-1 receptor agonist should prioritize agents with documented cardiovascular benefits, and the medication should not be used in combination with dipeptidyl peptidase-4 (DPP-4) inhibitors 1.

In terms of specific medications, dulaglutide has been shown to produce similar glycemic control to insulin glargine, but with a significantly slower decline in GFR 1. Semaglutide is also a viable option, and its oral formulation may be beneficial for patients who have difficulty with injections 1.

Overall, the use of GLP-1 receptor agonists in patients with type 2 diabetes and impaired renal function is supported by strong evidence, and they should be considered as a first-line treatment option for these patients. Regular blood glucose monitoring is essential, with target fasting glucose of 90-130 mg/dL and post-meal levels below 180 mg/dL, though targets may be relaxed for older patients or those at high hypoglycemia risk.

From the FDA Drug Label

The mean eGFR at baseline was 79 mL/min/1.73 m2 and 41. 8% of patients had mild renal impairment (eGFR 60 to 90 mL/min/1.73m2), 20.7% had moderate renal impairment (eGFR 30 to 60 mL/min/1.73m2) and 2.4% of patients had severe renal impairment (eGFR < 30 mL/min/1.73m2).

The preferred treatment for type 2 diabetes with impaired renal function is not explicitly stated in the provided drug label. However, the label does mention that 41.8% of patients had mild renal impairment and 20.7% had moderate renal impairment in the LEADER trial, and liraglutide (VICTOZA) was used in these patients.

• Key points:
  • The label does not directly compare GLP-1 receptor agonists and insulin therapy in patients with impaired renal function.
  • The label does provide information on the use of liraglutide (VICTOZA) in patients with renal impairment, but it does not specify whether it is the preferred treatment.
  • Liraglutide (VICTOZA) was used in patients with mild and moderate renal impairment in the LEADER trial, but the label does not provide information on its use in patients with severe renal impairment 2.

From the Research

Treatment Options for Type 2 Diabetes with Impaired Renal Function

The treatment of type 2 diabetes with impaired renal function can be challenging due to the limited options available. However, two potential treatment options are Glucagon-like peptide-1 (GLP-1) receptor agonists and insulin therapy.

GLP-1 Receptor Agonists

• GLP-1 receptor agonists have been shown to be effective in reducing HbA1c levels and have a lower risk of hypoglycemia compared to insulin therapy 3.
• They also have the potential to prevent renal complications of type 2 diabetes 3.
• A study comparing dulaglutide, a GLP-1 receptor agonist, to insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease found that dulaglutide produced similar glycaemic control with reduced decline in eGFR 4.

Insulin Therapy

• Insulin therapy is a common treatment option for type 2 diabetes, but it can be challenging to initiate and intensify, especially in patients with impaired renal function 5.
• Insulin analogues, such as insulin detemir, have been shown to be effective in reducing HbA1c levels and have a lower risk of hypoglycemia compared to traditional insulin 6.
• However, insulin therapy may not be as effective in preventing renal complications of type 2 diabetes as GLP-1 receptor agonists 3, 4.

Comparison of GLP-1 Receptor Agonists and Insulin Therapy

• A review of the literature found that GLP-1 receptor agonists and basal insulin therapies are effective treatment options for insulin-naïve patients with suboptimal glycemic control with oral hypoglycemic agents 7.
• However, the relative positioning of these therapies within the type 2 diabetes treatment paradigm is still unclear and requires further comparative data 7.
• A study comparing dulaglutide to insulin glargine found that dulaglutide was associated with higher rates of nausea and diarrhea, but lower rates of symptomatic hypoglycemia 4.