From KSAP 10/19 61
A 44-year-old man with CKD secondary to reflux nephropathy is seen for routine care. He has been well but has gained 4 kg since his last visit. He leads a sedentary lifestyle and travels extensively for work. Six months ago, his hemoglobin A1C was 7.1%, and he had hoped to intensify his exercise regimen by joining a local gym.
His medications include amlodipine and lisinopril. Although he has medical insurance, he must pay out of pocket for most of his medications.
On physical examination, he appears well, and his blood pressure is 138/82 mm Hg. His heart rate is 86/min, and his body mass index is 31 kg/m2. The physical examination is normal except for trace lower extremity edema.
Result Reference Range
Creatinine 2.5 mg/dL 0.7–1.3
Estimated glomerular filtration rate (eGFR) 30 mL/min per 1.73 m2 >90
Hemoglobin A1c 8% (estimated average glucose 183 mg/dL) 4–5.6
Urine albumin-to-creatinine ratio 78 mg/g <30
In addition to encouraging ongoing efforts at a heart healthy lifestyle with exercise and dietary changes, what is the MOST appropriate addition to his regimen?
AGlyburideBGlipizideCMetforminDGlimepirideECanagliflozinAnswer & ExplanationCorrect Answer is: B
Glipizide
The most appropriate agent for the treatment of diabetes mellitus (DM) in this patient is glipizide.
Glycemic control is important for patients with CKD and perhaps even more important for those with CKD attributed to diabetic nephropathy. Sulfonylureas bind to a receptor on pancreatic islet cells and promote release of insulin. These agents can cause hypoglycemia. Both glyburide and glimepiride are primarily cleared by the kidney and use of these agents when the eGFR is <60 mL/min per 1.73 m2 is not recommended. In contrast, only 10% of glipizide is renally cleared, so this agent can be used for a patient with stage 3 CKD. Nevertheless, caution is still required with glipizide, because it can cause hypoglycemia and may accumulate in patients with eGFR <30 mL/min per 1.73 m2.
Sulfonylureas have been supplanted by sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor antagonists (GLP1-RA) as preferred oral agents for glycemic control in type II DM, as these newer agents have superior effects on cardiovascular and renal outcomes. However, sulfonylureas still have a role due to their low cost and efficacy in lowering blood sugar. In addition, safety data for the use of SGLT-2 inhibitors and GLP1-RA are limited in patients with advanced impairment of GFR. SGLT-2 inhibitors such as canagliflozin can cause volume depletion because of glycosuria with osmotic diuresis, and cases of AKI have occurred. Recent trial data suggests these agents may be safe in patients with eGFR as low as 20 mL/min per 1.73 m2, but they are not currently recommended for individuals with eGFR <45 mL/min per 1.73 m2
Metformin increases insulin sensitivity and decreases hepatic gluconeogenesis, but it does not cause hypoglycemia. This is also an attractive medication because it sometimes leads to weight loss. For these reasons and its low cost and good safety profile, metformin is the preferred initial agent for treatment of type II DM, provided kidney function is preserved. Metformin is filtered and also secreted by the organic cation transporters in the proximal tubule. Metformin can accumulate in patients with CKD and, rarely, can cause lactic acidosis. For this reason, the Food and Drug Administration (FDA) recommends that clinicians reduce the dosage of metformin for those with eGFR in the 30–45 mL/min per 1.73 m2 range; when eGFR is <30 ml/min per 1.73 m2, it should be discontinued altogether.
References
Neumiller JJ, Alicic RZ, Tuttle KR: Therapeutic considerations for antihyperglycemic agents in diabetic kidney disease. J Am Soc Nephrol 28(8): 2263–2274, 2017
Hahr A, Molitch M: Management of diabetes mellitus in patients with chronic kidney disease. Clin Diabetes Endocrinol. Available at: https://clindiabetesendo.biomedcentral.com/articles/10.1186/s40842-015-0001-9. Accessed December 5, 2018
American Diabetes Association: 9 Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes— 2019. Diabetes Care 42 (Suppl. 1): S90–S102, 2019