What is the initial treatment for patients with diabetes and impaired renal function, specifically those with an estimated glomerular filtration rate (eGFR) of 30 mL/minute/1.73 m² or higher?

From the Guidelines

For patients with diabetes and impaired renal function with an eGFR of 30 mL/minute/1.73 m² or higher, metformin is generally recommended as the initial treatment. The typical starting dose is 500 mg once or twice daily with meals, which can be gradually increased to a maximum of 2000 mg daily in divided doses as tolerated. However, dose adjustment is necessary based on renal function: for patients with eGFR 45-59 mL/min/1.73 m², the maximum dose should be reduced to 1000-1500 mg daily, while those with eGFR 30-44 mL/min/1.73 m² should receive no more than 500-1000 mg daily. Regular monitoring of renal function is essential, with assessments recommended every 3-6 months. Metformin works by decreasing hepatic glucose production and improving insulin sensitivity, making it effective for glycemic control while having a low risk of hypoglycemia. It also offers cardiovascular benefits and is weight-neutral or may promote modest weight loss. If metformin is contraindicated or not tolerated, alternative first-line options include SGLT-2 inhibitors (particularly those with proven renal benefits like empagliflozin or dapagliflozin) or GLP-1 receptor agonists, which have demonstrated cardio-renal protective effects in this population 1.

Some key points to consider when treating patients with diabetes and impaired renal function include:

• Monitoring renal function regularly to adjust medication doses as needed
• Considering the use of SGLT-2 inhibitors or GLP-1 receptor agonists in patients who cannot tolerate metformin or require additional therapy
• Being aware of the potential risks and benefits of each medication, including the risk of lactic acidosis with metformin and the potential for cardiovascular benefits with SGLT-2 inhibitors and GLP-1 receptor agonists
• Individualizing treatment based on patient factors, such as comorbidities and medication tolerance 1.

Overall, the goal of treatment is to achieve optimal glycemic control while minimizing the risk of adverse effects and promoting cardiovascular and renal health.

From the FDA Drug Label

Metformin hydrochloride extended-release tablets are contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m². Initiation of metformin hydrochloride extended-release tablets in patients with an eGFR between 30 to 45 mL/minute/1.73 m² is not recommended.

The initial treatment for patients with diabetes and impaired renal function, specifically those with an eGFR of 30 mL/minute/1.73 m² or higher, is metformin if the eGFR is ≥30 mL/minute/1.73 m². However, according to the drug label, initiation of metformin is not recommended in patients with an eGFR between 30 to 45 mL/minute/1.73 m².

• Key points:
  • Metformin is contraindicated in patients with an eGFR below 30 mL/minute/1.73 m².
  • Initiation of metformin is not recommended in patients with an eGFR between 30 to 45 mL/minute/1.73 m².
  • Patients with an eGFR of 45 mL/minute/1.73 m² or higher can be considered for metformin therapy. 2

From the Research

Initial Treatment for Patients with Diabetes and Impaired Renal Function

• Patients with diabetes and an estimated glomerular filtration rate (eGFR) of 30 mL/minute/1.73 m² or higher may begin with metformin as their initial treatment 3.
• A sodium-glucose cotransporter-2 (SGLT2) inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist can be considered as a second-line option, with certain caveats 4.

Considerations for SGLT2 Inhibitors and GLP-1 Receptor Agonists

• SGLT2 inhibitors are most effective when the eGFR is more than 60 ml per min per 1·73m2 at initiation and should be avoided in patients at risk of diabetic ketoacidosis 4.
• GLP-1 receptor agonists are contraindicated in patients with a history of medullary thyroid cancer and should be used with caution in patients with a history of pancreatitis of a known cause 4.

Estimating Glomerular Filtration Rate (eGFR)

• The CKD-EPI equation is one of the most accurate equations for estimating eGFR, especially in patients with advanced chronic kidney disease 5.
• The accuracy of eGFR equations can vary depending on the patient's age, sex, and underlying kidney disease 5.

Kidney Disease Progression and Mortality

• Patients with type 2 diabetes and impaired renal function are at a higher risk of kidney disease progression and all-cause mortality compared to those without diabetes 6.
• The presence of albuminuria is associated with accelerated eGFR decline, independent of diabetes status 6.

Predictors of Rapid eGFR Progression

• Factors such as increasing age, partial health insurance coverage, history of smoking, and angiotensin-receptor blockade use are associated with rapid eGFR progression in patients with diabetes and/or hypertension 7.
• Metformin use has been shown to be protective against rapid eGFR progression in these patients 7.