Should a patient with uncontrolled type 2 diabetes mellitus, currently on Metformin (metformin) and Gliclazide (gliclazide), with impaired renal function (Creatinine 1.4), continue the same medications?

From the Guidelines

The patient's current medication regimen of metformin and gliclazide should be adjusted due to concerns about both glycemic control and kidney function, with consideration of reducing or discontinuing metformin if the estimated GFR is below 45 ml/min, and adding a medication with lower risk in renal impairment, such as an SGLT-2 inhibitor or a GLP-1 receptor agonist, as recommended by the KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease 1. The current combination of metformin and gliclazide is not adequately controlling the diabetes, and the elevated creatinine of 1.4 indicates reduced kidney function.

• Metformin should be used cautiously or potentially discontinued as it can accumulate with impaired renal function, increasing the risk of lactic acidosis.
• For this patient, consider reducing the metformin dose if estimated GFR is 30-45 ml/min, or discontinuing it if below 30 ml/min, as suggested by the KDIGO guideline 1.
• Adding a medication with lower risk in renal impairment would be appropriate, such as an SGLT-2 inhibitor, which has been shown to offer substantial benefits in reducing risks for CKD and CVD, as reported in the 2020 KDIGO clinical practice guideline synopsis 1.
• Alternatively, GLP-1 receptor agonists could be considered as they provide effective glucose control with low hypoglycemia risk and potential cardiovascular benefits, as mentioned in the 2021 Annals of Internal Medicine article 1. The patient should also have comprehensive kidney function assessment including eGFR and urine albumin-to-creatinine ratio to better guide medication choices and monitor for diabetic kidney disease progression.
• The KDIGO guideline recommends monitoring eGFR in patients treated with metformin and adjusting the dose when the eGFR is <45 ml/min per 1.73 m2, and for some patients when the eGFR is 45–59 ml/min per 1.73 m2 1.
• The patient's kidney function and medication regimen should be closely monitored to minimize the risk of adverse events, such as lactic acidosis, and to optimize glycemic control and kidney outcomes.

From the FDA Drug Label

Renal impairment — The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney. Clinical recommendations based upon the patient's renal function include [see Dosage and Administration ( 2.1), Clinical Pharmacology ( 12. 3)] : Before initiating metformin hydrochloride tablets, obtain an estimated glomerular filtration rate (eGFR). Metformin hydrochloride tablets are contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2[see Contraindications ( 4) ]. Initiation of metformin hydrochloride tablets is not recommended in patients with eGFR between 30 to 45 mL/min/1. 73 m 2. Obtain an eGFR at least annually in all patients taking metformin hydrochloride tablets. In patients at risk for the development of renal impairment (e.g., the elderly), renal function should be assessed more frequently. In patients taking metformin hydrochloride tablets whose eGFR falls below 45 mL/min/1. 73 m 2, assess the benefit and risk of continuing therapy.

The patient's creatinine (Cr) level is 1.4, which may indicate some degree of renal impairment, although the exact eGFR is not provided. Given the potential risk of lactic acidosis associated with metformin, especially in patients with renal impairment, it is essential to assess the benefit and risk of continuing metformin therapy in this patient. Considering the patient's uncontrolled diabetes and renal function, it may be necessary to re-evaluate the treatment plan and consider alternative therapies or adjust the metformin dose based on the patient's renal function, as recommended in the drug label 2. Glicazide is not addressed in the provided drug label, so no conclusion can be drawn about its use in this patient. The decision to continue or modify the current medication regimen should be made under the guidance of a healthcare provider, taking into account the patient's overall clinical condition and renal function.

From the Research

Patient's Current Medications and Condition

• The patient is currently taking metformin and glicazide for type 2 diabetes.
• The patient's diabetes is uncontrolled, and their creatinine (Cr) level is 1.4.

Considerations for Continuing Current Medications

• According to 3, metformin is safe and effective as monotherapy or in combination with other antihyperglycemic agents in type 2 diabetic patients requiring additional glycemic control.
• However, the patient's diabetes is uncontrolled, suggesting that the current medication regimen may not be sufficient.
• 4 mentions that metformin is widely considered to be the optimal initial therapy for patients with type 2 diabetes mellitus, but its use in patients with mild to moderate chronic kidney disease has been reevaluated, and regulations guiding its use have become more lenient.

Alternative Treatment Options

• 5 explores the use of premixed insulin, metformin, and a glucagon-like peptide 1 receptor agonist as combination therapy for type 2 diabetes, showing improved glycemic control over 12 months.
• 6 discusses the combination of sodium-glucose cotransporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor in type 2 diabetes, showing better glycemic control and greater weight reduction without increasing the risk of hypoglycemia and urinary tract infection.
• 7 evaluates the comparative safety and efficacy of all available classes of antihyperglycemic therapies in patients with type 2 diabetes inadequately controlled with metformin and sulphonylurea combination therapy, suggesting that third-line agents differ in their propensity to cause weight gain and hypoglycemia.

Renal Impairment Considerations

• The patient's Cr level is 1.4, indicating mild renal impairment.
• 3 mentions that lactic acidosis risk is minimal with metformin, provided that contraindications, particularly renal impairment, and prescribing guidelines are respected.
• 4 notes that regulations guiding metformin's use in patients with stable, modest renal dysfunction have become more lenient in recent years.