What is the best diabetic medication for a patient with stage 3 Chronic Kidney Disease (CKD) and Impaired Renal Function?

From the Guidelines

For patients with stage 3 chronic kidney disease and diabetes, SGLT-2 inhibitors such as empagliflozin or dapagliflozin are recommended as the first-line medication due to their kidney protection and cardiovascular benefits, as evidenced by the most recent study 1.

Key Considerations

• The selection of specific agents may depend on comorbidity and CKD stage, with SGLT2 inhibitors being more useful for patients at high risk of CKD progression 1.
• Medication selection should be individualized based on the patient's specific eGFR, albuminuria status, cardiovascular risk, hypoglycemia risk, and cost considerations.
• Regular monitoring of kidney function is essential, as medication dosages may need adjustment as kidney function changes.

Medication Options

• SGLT-2 inhibitors: empagliflozin (10-25 mg daily) or dapagliflozin (5-10 mg daily) are particularly beneficial for patients with stage 3 CKD and diabetes, as they offer kidney protection and have demonstrated cardiovascular benefits 2, 1.
• GLP-1 receptor agonists: semaglutide or liraglutide are excellent options with proven cardiovascular benefits and weight loss effects, although their use in CKD patients is still being studied 2, 1.
• Metformin: can be used as a first-line medication if eGFR is above 30 ml/min/1.73m², with a typical starting dose of 500 mg once or twice daily, titrated up to a maximum of 1,000 mg twice daily as tolerated 3.

Dose Adjustments

• SGLT2 inhibitors: can be continued in patients with eGFR below 30 mL/min/1.73 m2 as long as they are well tolerated and kidney replacement therapy is not imminent 2.
• GLP-1 receptor agonists: no dose adjustment is required for dulaglutide, liraglutide, and injectable semaglutide, although caution is advised when initiating or increasing the dose of exenatide 3.

From the FDA Drug Label

The CREDENCE trial was a multinational, randomized, double-blind, placebo-controlled trial comparing canagliflozin with placebo in adult patients with type 2 diabetes mellitus, an eGFR ≥ 30 to < 90 mL/min/1.73 m^2 and albuminuria (urine albumin/creatinine > 300 to ≤ 5,000 mg/g) who were receiving standard of care including a maximum-tolerated, labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) The primary objective of CREDENCE was to assess the efficacy of canagliflozin relative to placebo in reducing the composite endpoint of end stage kidney disease (ESKD), doubling of serum creatinine, and renal or CV death. Canagliflozin 100 mg significantly reduced the risk of the primary composite endpoint based on a time-to-event analysis [HR: 0.70; 95% CI: 0.59, 0.82; p<0.0001] The treatment effect reflected a reduction in progression to ESKD, doubling of serum creatinine and cardiovascular death

Key Points:

• Canagliflozin has been shown to reduce the risk of end stage kidney disease (ESKD), doubling of serum creatinine, and renal or CV death in patients with type 2 diabetes mellitus and impaired renal function.
• The CREDENCE trial demonstrated a significant reduction in the primary composite endpoint with canagliflozin 100 mg compared to placebo.
• Canagliflozin may be a suitable option for patients with stage 3 Chronic Kidney Disease (CKD) and impaired renal function, as it has been shown to slow the progression of kidney disease and reduce the risk of cardiovascular events.

Based on the CREDENCE trial results, canagliflozin may be considered a suitable option for patients with stage 3 CKD and impaired renal function 4.

From the Research

Diabetic Medication Options for Patients with Stage 3 CKD and Impaired Renal Function

• Metformin is still considered an adequate choice for patients with stage 3 CKD, as long as proper dose adjustments are made based on renal function 5.
• Sulfonylureas with limited renal clearance, such as gliquidone, glipizide, and gliclazide, can be used as an alternative to metformin and are more effective than repaglinide in terms of glycemic control 5.
• DPP-4 inhibitors, such as linagliptin, can be used across all stages of renal impairment without dosing restrictions or concerns regarding dose escalation 6.
• SGLT2 inhibitors, such as canagliflozin and empagliflozin, have shown potential benefits in reducing the risk of adverse renal and cardiovascular events, but are contraindicated when eGFR <45 mL/min/1.73m2 6, 7.
• GLP-1 agonists, such as liraglutide and semaglutide, have also shown potential benefits in reducing the risk of adverse renal and cardiovascular events 6.

Considerations for Treatment

• Achieving optimal glycemic control is the first therapeutic goal in the management of DM-CKD 5.
• The choice of diabetic medication should be individualized based on the patient's renal function, glycemic control, and other comorbidities 6, 8.
• Patients with stage 3 CKD require regular monitoring of their renal function, glycemic control, and other comorbidities to adjust their treatment plan as needed 8.
• SGLT2 inhibitors and GLP-1 agonists have shown potential benefits in reducing the risk of adverse renal and cardiovascular events, but their use should be carefully evaluated based on the patient's renal function and other comorbidities 6, 7.

Safety Profile of Diabetic Medications

• SGLT2 inhibitors probably increase the risk of genital infections and slightly increase creatinine levels, but may reduce the risk of heart failure, hyperkalaemia, and cardiovascular death 9.
• DPP-4 inhibitors may have little or no effect on cardiovascular death, weight, and hypoglycaemia, but may reduce HbA1c levels 9.
• GLP-1 agonists may reduce HbA1c levels and weight, but their safety profile is uncertain 9.
• The safety profile of other diabetic medications, including insulin, is limited by the availability of high-quality studies 9.