What is a suitable oral hypoglycemic agent for diabetic control in a patient with Impaired renal function (Renal Disease)?

From the Guidelines

For patients with diabetes and renal disease, SGLT2 inhibitors like empagliflozin (10-25 mg daily) or dapagliflozin (5-10 mg daily) are excellent choices as they provide both glycemic control and renal protection by reducing albuminuria and slowing kidney disease progression, as supported by the most recent evidence from 1.

Key Considerations

• Metformin is often the first-line oral agent if eGFR is above 30 ml/min/1.73m², though dose reduction is needed when eGFR falls below 45, as indicated in 1 and 1.
• GLP-1 receptor agonists, while primarily injectable, now include oral semaglutide (Rybelsus, 3-14 mg daily) which offers cardiovascular benefits and is safe in renal impairment, as noted in 1.
• DPP-4 inhibitors such as linagliptin (5 mg daily) require no dose adjustment in kidney disease and are well-tolerated, as stated in 1 and 1.
• Sulfonylureas should generally be avoided or used cautiously with dose reduction due to increased hypoglycemia risk in renal impairment, as warned in 1 and 1.

Treatment Selection

Treatment selection should consider the degree of renal impairment, hypoglycemia risk, and comorbidities, with medication doses adjusted according to kidney function to ensure both effective diabetes management and kidney protection, as emphasized in 1, 1, and 1.

Renal Protection

SGLT2 inhibitors have been shown to provide renal protection by reducing albuminuria and slowing kidney disease progression, as demonstrated in 1.

Cardiovascular Benefits

GLP-1 receptor agonists, including oral semaglutide, offer cardiovascular benefits, as noted in 1 and 1.

From the FDA Drug Label

A total of 1,261 patients with type 2 diabetes mellitus inadequately controlled on basal insulin alone or basal insulin in combination with oral drugs participated in a randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy of TRADJENTA as add-on therapy to basal insulin over 24 weeks. Randomization was stratified by baseline HbA1c (<8.5% vs ≥8. 5%), renal function impairment status (based on baseline eGFR), and concomitant use of oral antidiabetic drugs (none, metformin only, pioglitazone only, metformin + pioglitazone) Patients with a baseline A1C of ≥7% and ≤10% were included in the trial including 709 patients with renal impairment (eGFR <90 mL/min), most of whom (n=575) were categorized as mild renal impairment (eGFR 60 to <90 mL/min). The difference between treatment with linagliptin and placebo in terms of adjusted mean change from baseline in HbA1c after 24 weeks was comparable for patients with no renal impairment (eGFR ≥90 mL/min, n=539), with mild renal impairment (eGFR 60 to <90 mL/min, n= 565), or with moderate renal impairment (eGFR 30 to <60 mL/min, n=124) A total of 133 patients with type 2 diabetes mellitus participated in a 52 week, double-blind, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of TRADJENTA in patients with both type 2 diabetes mellitus and severe chronic renal impairment

Linagliptin is a suitable oral hypoglycemic agent for diabetic control in patients with impaired renal function (renal disease) 2.

• It can be used in patients with mild, moderate, or severe renal impairment.
• The efficacy of linagliptin in patients with renal impairment is comparable to that in patients with no renal impairment.

From the Research

Suitable Oral Hypoglycemic Agents for Diabetic Control in Patients with Impaired Renal Function

• Metformin is globally accepted as the first choice for diabetic subjects, including those with impaired renal function, provided that their estimated Glomerular Filtration Rate (eGFR) remains above 30 mL/min per square meter 3.
• For diabetic patients with eGFR between 30-60 mL/min per square meter, more frequent monitoring of renal function and dose reduction of metformin is needed 3.
• Dipeptidyl peptidase-4 (DPP-4) inhibitors are useful drugs for patients with impaired renal function, as they do not cause hypoglycemia, but most of them require dose reduction in various stages of renal disease, except for linagliptin 4, 3, 5.
• Linagliptin can be used across all stages of renal impairment without dosing restrictions or concerns regarding dose escalation 5.
• Sulfonylureas and glinides carry a higher risk of hypoglycemia in patients with impaired renal function and must be used with caution, with lower doses and slower titration of the dose 3, 6.
• SGLT2 inhibitors have reduced efficacy and their safety remains to be demonstrated in the presence of chronic kidney disease (CKD), and are contraindicated when eGFR <45 mL/min/1.73m2 4, 5.

Considerations for Patients with Advanced CKD

• Insulin injection therapy remains the mainstay of treatment in diabetic patients with moderate to advanced CKD, particularly in those receiving dialysis therapy 6.
• Repaglinide and mitiglinide are rapid- and short-acting insulinotropic SU receptor ligands that are rarely accompanied by hypoglycemia and are attractive therapeutic options even in the dialysis population 6.
• Alpha-glucosidase inhibitors are rarely accompanied by hypoglycemia, but their use is not recommended in patients with advanced stage CKD and on dialysis 6.