What medications are suitable for people with Impaired renal function (Chronic Kidney Disease, CKD) and Diabetes Mellitus Type 2?

From the Guidelines

For people with Type 2 diabetes and chronic kidney disease (CKD), metformin should be considered the first-line treatment, and SGLT2 inhibitors like empagliflozin or dapagliflozin are strongly recommended for their kidney protection and cardiovascular benefits, as evidenced by the most recent study 1. When selecting medications for patients with Type 2 diabetes and CKD, it is crucial to consider the stage of CKD and the presence of other comorbidities.

• Metformin is recommended for patients with eGFR ≥30 mL/min/1.73 m², with dose adjustments as necessary, as per the FDA guidance 1.
• SGLT2 inhibitors are recommended for patients with eGFR ≥20 mL/min/1.73 m², as they have been shown to slow CKD progression and reduce heart failure risk independent of glucose management 1.
• GLP-1 receptor agonists, such as semaglutide or dulaglutide, are excellent options for patients who require additional glucose-lowering therapy or have established cardiovascular disease, as they offer cardiovascular benefits and do not require dose adjustment in CKD 1.
• DPP-4 inhibitors like linagliptin are safe across all CKD stages without dose adjustment, making them a viable option for patients with CKD 1.
• Sulfonylureas should be used cautiously, with glipizide preferred over others that accumulate in kidney disease, and insulin therapy may be necessary, with doses potentially requiring reduction as kidney function declines 1. Regular monitoring of kidney function, blood glucose, and medication side effects is essential, with medication adjustments as CKD progresses to prevent hypoglycemia and other complications, as highlighted in the studies 1.

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 Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial (CREDENCE) 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 2and 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)

Medications suitable for people with Impaired renal function (Chronic Kidney Disease, CKD) and Diabetes Mellitus Type 2:

• Liraglutide (SQ): may be suitable, as the study included patients with mild, moderate, and severe renal impairment, but the label does not provide explicit dosing recommendations for patients with impaired renal function 2.
• Canagliflozin (PO): may be suitable, as the CREDENCE trial specifically included patients with eGFR ≥ 30 to < 90 mL/min/1.73 m2 and albuminuria, and canagliflozin was compared to placebo in this population 3.

From the Research

Medications for Impaired Renal Function and Diabetes Mellitus Type 2

• Metformin is considered a suitable initial pharmacological option for patients with type 2 diabetes mellitus, including those with mild to moderate chronic kidney disease (CKD) 4, 5.
• The risk of lactic acidosis associated with metformin use in individuals with impaired kidney function is considered low, with an overall incidence of approximately 3-10 per 100,000 person-years 4.
• However, some studies suggest that metformin may have an adverse effect on renal function in patients with type 2 diabetes and moderate CKD 6.
• Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to have a salutary effect on long-term estimated glomerular filtration rate and may be beneficial for patients with type 2 diabetes and CKD 7, 8.
• Dose adjustments and careful monitoring of kidney function are essential when using metformin in patients with CKD 5.
• GLP-1RAs and SGLT-2is have been shown to improve renal resistive index, a useful measure to study diabetic kidney disease and predict its evolution 8.

Key Considerations

• Patients with type 2 diabetes and CKD should be carefully evaluated and monitored when initiating or continuing metformin therapy 4, 5, 6.
• SGLT-2is and GLP-1RAs may be suitable alternatives or additions to metformin therapy for patients with type 2 diabetes and CKD 7, 8.
• Dosage adjustments and sick-day education are essential for the safe use of metformin in patients with CKD 5.