From the Guidelines
Oral hypoglycemic medications cannot be given to patients with chronic kidney disease (CKD) due to safety concerns and altered drug metabolism, and insulin therapy is often the safest and most effective treatment option. Many oral antidiabetic drugs are cleared by the kidneys, leading to drug accumulation and increased risk of hypoglycemia in CKD patients 1. Metformin, the first-line agent for type 2 diabetes, is contraindicated in advanced CKD (eGFR <30 ml/min) due to the risk of lactic acidosis 1. Sulfonylureas like glipizide and glyburide can cause prolonged hypoglycemia in CKD patients as their active metabolites accumulate 1.
Some key points to consider when managing diabetes in CKD patients include:
- Metformin is contraindicated in advanced CKD (eGFR <30 ml/min) due to the risk of lactic acidosis 1
- SGLT2 inhibitors can be initiated with eGFR 20–29 ml/min/1.73 m2 and continued at lower eGFR if previously initiated and well-tolerated, but have minimal effects on glycemia in this range of eGFR 1
- GLP-1 receptor agonists have been studied with eGFR as low as 15 ml/min/1.73 m2 and retain glucose-lowering potency across the range of eGFR and among dialysis patients 1
- DPP-4 inhibitors (sitagliptin, linagliptin) are safer options but require dose adjustments 1
According to the most recent and highest quality study, insulin therapy is the recommended treatment option for most CKD patients with diabetes, as it is not excreted by the kidneys, though doses must be carefully titrated due to decreased insulin clearance in kidney disease 1.
From the FDA Drug Label
Do not take metformin hydrochloride tablets if you: have kidney problems You have a higher chance of getting lactic acidosis if you: have kidney problems. People whose kidneys are not working properly should not take metformin hydrochloride tablets.
Oral hyperglycemic medications like metformin cannot be given to patients with Chronic Kidney Disease (CKD) because they have a higher chance of developing lactic acidosis, a rare but serious side effect that can cause death. This is because kidney problems can lead to a buildup of lactic acid in the blood, which can be fatal. Therefore, it is recommended that patients with CKD should not take metformin hydrochloride tablets unless their kidney function has been checked and is normal 2.
From the Research
Oral Hyperglycemic Agents in CKD
- Oral hyperglycemic agents, such as sulfonylurea, are not suitable for patients with chronic kidney disease (CKD) due to the risk of prolonged hypoglycemia 3.
- Metformin is contraindicated in moderate to advanced CKD, although recent guidelines have relaxed this restriction to permit therapy if the glomerular filtration rate (GFR) is > 30 mL/min 4, 5.
- The risk of lactic acidosis is a concern with metformin use in CKD patients, but epidemiological evidence suggests that this fear is disproportionate 4, 6.
- Other oral antidiabetic agents, such as repaglinide and mitiglinide, may be used in patients with CKD, but their use is limited by the risk of hypoglycemia and other adverse effects 3.
- Dipeptidyl peptidase-4 inhibitors and incretin mimetics are new antihyperglycemic agents that may be used in patients with CKD, but their safety and efficacy in this population are still being studied 3, 7.
Glycemic Control in CKD
- Glycemic goals should be individualized for patients with CKD, considering the severity of CKD, presence of macrovascular and microvascular complications, and life expectancy 7.
- A general hemoglobin A1c (HbA1c) goal of approximately 7% may be appropriate in earlier stages of CKD, with more relaxed targets often appropriate in later stages 7.
- Sodium glucose cotransporter2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to improve kidney and heart outcomes in patients with diabetes and CKD, irrespective of HbA1c targets 7.
Safety Considerations
- The use of oral hyperglycemic agents in CKD patients requires careful consideration of the risks and benefits, including the risk of hypoglycemia, lactic acidosis, and other adverse effects 3, 4, 6, 5.
- Patients with CKD should be closely monitored for signs of hypoglycemia and lactic acidosis, and their medication regimen should be adjusted accordingly 3, 6.