Joslin Diabetes Center Joslin Diabetes Forum 2013: The Impact of Comorbidities on Glucose Control Scenario 2: Reduced Renal Function

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1 Scenario 2: Reduced Renal Function 62 y.o. white man with type 2 diabetes for 18 years Hypertension and hypercholesterolemia Known proliferative retinopathy Current medications: Metformin 1000 mg bid Glyburide 10 mg bid Pioglitazone 30 mg daily Lisinopril 40 mg daily Atorvastatin 40 mg daily Aspirin 81 mg daily Glucose checking 1 2x daily; most < 180 mg/dl Mild hypoglycemic reactions every week or two Overall, feels well and has good energy Eats 3 regular meals & tries to exercise 30 min on treadmill at least every other day 1

2 BP 132/78, pulse 76, BMI 28.3 kg/m 2 Funduscopy: several hemorrhages and exudates No carotid bruits but pedal pulses are barely palpable Chest is clear Heart: WNL Neurologic exam: vibratory sensation decreased but able to feel monofilament in all toes; AJ reflexes absent Initial laboratory testing A1C: 6.6% LDL cholesterol: 68 mg/dl Serum creatinine: 1.4 mg/dl egfr: 41 ml/min/1.73 m 2 Urine albumin/creatinine ratio: 372 mg/g creatinine Renal Disease (Slide 1 of 2) Sulfonylureas Meglitinides -Glucosidase (Acarbose, Miglitol) TZDs (Pioglitazone) Do not use if: egfr < 60 (nateglinide) Cr >2 (~egfr < 30) Other notes Glipizide: less hypoglycemia Repaglinide: no dose adjustment Concerns re: fluid retention, edema, bone disease, bladder Ca Renal Disease (Slide 2 of 2) Use with caution if: Adjust dose if: Do not use if: Other notes Biguanides (Metformin) egfr GLP-1 Agonists egfr (maximum 1000 mg/d) egfr < 30 egfr < 30 (exenatide) D/C for inpatients if lactic acidosis risk Liraglutide: no dose adjustment DPP-4 SGLT-2 egfr 50 egfr (max 100 mg/d) egfr < 45 2

3 Glycemic Control and Progressing Diabetic Nephropathy In the patient who is developing a progressive fall in GFR, several things need to be considered: Decreases in insulin sensitivity Decreased renal gluconeogenesis Decreased clearance of insulin Decreased clearance of antihyperglycemic medications Changes in body composition Anorexia, gastroparesis, weight loss Increased cardiovascular risk Need for risk modification: BP, lipids, ASA CKD Progresses in Stages Defined by Kidney Function: GFR CKD Stage Description GFR (ml/min/1.73 m 2 ) 1 Kidney damage with 90 normal or GFR 2 Kidney damage with mild GFR 3a 3b Moderate GFR Severe GFR Kidney failure <15 or dialysis NKF. Am J Kidney Dis. 2002;39(2 suppl 1):S1-S266. At age 62, with serum creatinine 1.7 mg/dl, his egfr is 41 ml/min/1.73m 2 Stage IIIb CKD Needs to adjust oral hypoglycemic medication Metformin 2000 mg daily Pioglitazone 30 mg daily Glyburide 20 mg daily Also at high risk for cardiovascular disease and needs aggressive CVD risk reduction 3

4 Treatment Concerns With Insulin With CKD Insulin clearance begins to decrease as egfr approaches 60 ml/min/1.73m 2 Hypoglycemic risk increases markedly Insulin doses can be halved as egfr approaches 45 ml/min/1.73m 2 with maintenance of glycemic control but reduction in hypoglycemia Glucose levels should be monitored closely; additional dose reductions may be needed as CKD progresses Treatment Concerns With Anti-DM Agents With CKD Sulfonylureas (glipizide, glyburide, glimepiride) Glipizide preferred less hypoglycemia than glyburide or glimepiride Meglitinides (repaglinide, nateglinide) Cannot use nateglinide with egfr < 60 Repaglinide: no dose adjustment needed for progressing CKD Disaccharidase inhibitors (acarbose, miglitol) Cannot use with creatinine > 2 mg/dl (~egfr < 30) Treatment Concerns With Use of Antihyperglycemic Medications and CKD Thiazolidinediones (pioglitazone) No dose adjustments needed for progressing CKD Fluid retention & edema; worse if nephrotic Bone disease; additive to renal osteodystrophy? Bladder Ca? Biguanides (metformin) egfr 45 60: use with caution egfr 30 45: maximum dose 1000 mg/d egfr < 30: discontinue Discontinue for inpatients if risk factors for lactic acidosis 4

5 Treatment Concerns With Use of Antihyperglycemic Medications and CKD GLP-1 receptor agonists Exenatide: discontinue for egfr < 30 Liraglutide: no dose adjustments necessary for progressing CKD DPP-4 inhibitors Sitagliptin Saxagliptin Alogliptin Linagliptin GFR > mg/d 5 mg/d 25 mg/d 5 mg/d GFR mg/d 2.5 mg/d 12.5 mg/d 5 mg/d GFR < mg/d 2.5 mg/d 6.25 mg/d 5 mg/d 5