Reducing hyperglycemia in older patients with chronic kidney disease may be best accomplished using incretin-based agents.
Lenore is 76 years old and has had type 2 diabetes mellitus (T2DM) for 25 years. She lives alone, but her daughter lives close to her and has brought her to see you today. The daughter is a patient of yours and her mother would like you to become her new primary care doctor.
Lenore’s current medications are metformin 850 mg twice daily; glipizide XL 2.5 mg daily; and lisinopril 10 mg daily. Her weight is 193 lb; BMI, 30; blood pressure, 142/85 mm Hg. Laboratory tests reveal the following results: GFR, 40 mL/min per 1.73m2; creatinine, 1.3 mg/mL; HbA1c, 7.7%. Lipid values are LDL, 130 mg/dL; HDL, 35 mg/dL; and, triglycerides, 350 mg/dL.
Her daughter reports that she has recently experienced 3 episodes of dizziness and shaking. Her blood sugar level was 55 to 60 mg/dL when this happened. The symptoms stopped after she drank 2 glasses of orange juice.
What medication(s) would you choose to treat this patient's T2DM? What would be your goal for HbA1C? Would you consider initiating any other treatment at this time?
Please leave your comments below; then see the next page for Dr Shahady's discussion of treatment options.
Lenore has class 3B chronic kidney disease (CKD; GFR 45 to 30 mL/min per 1.73m2) and so I would immediately reduce the metformin dose by half, to 850 mg daily. Some clinicians would probably stop the metformin completely. Renal function should be closely monitored in patients with class 3B CKD; once GFR is <30 mL/min per 1.73m2, metformin should be stopped.1 She also has symptomatic hypoglycemia, most likely caused by the glipizide, so I would stop that immediately.
The challenge now is to decide what agent to use to control Lenore’s blood sugar level, in light of her CKD. Insulin might be a logical choice, but the patient is obese and has a history of hypoglycemia when taking even low-dose sulfonylurea. A dipeptidyl peptidase-4 (DPP-4) inhibitor such as linagliptin has very low renal clearance so would be an option, but it is only shown to reduce HbA1C by 0.4% to 0.7%. The other DPP-4 inhibitors (eg, saxagliptin, sitagliptin) have significant renal clearance and so the dose would need to be reduced. A glucagon-like peptide-1 (GLP-1) agonist would be my choice. Exenatide is eliminated via the kidney, so the dose should be reduced once GFR <50 mL/min per 1.73 m2 and not used with GFR <30 mL/min per 1.73 m2. Liraglutide has minimal renal clearance and can be used safely in patients with CKD. It will provide about 1% reduction in HbA1C. There is also evidence that GLP-I agonists reduce triglyceride levels and systolic blood pressure.2
I would be happy to reach an HbA1C level of <8% and would not push her to an HbA1C level of <7%, given her CKD, her age, and her long history of diabetes.
I would also begin therapy with a statin. Cardiovascular disease is the major cause of death in patients with CKD, and statins have demonstrated success in reducing CVD in these patients.3
1. Lipska KJ, Bailey CJ, Inzucchi SE. Use of metformin in the setting of mild-to-moderate renal insufficiency. Diabetes Care. 2011;34:1431-1437.
2. Reid T. Choosing GLP-1 receptor agonists or DPP-4 inhibitors: weighing the clinical trial evidence. Clin Diabetes. 2012;30:3-12.
3. Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomized placebo-controlled trial. Lancet. 2011;377:2181-2192.