2. Renal Impairment

Acarbose should be avoided in patients with an estimated glomerular filtration rate (eGFR) less than 25 mL/minute/ 1.73m2. Miglitol should be avoided in patients with an eGFR less than 25 mL/minute/ 1.73m2^1-4.

Metformin should be used cautiously in patients with an eGFR below 60 mL/ minute/1.73m2. Renal function should be closely monitored in patients with an eGFR of 30-59 mL/ minute/1.73m2, with doses decreased by 50% in patients with an eGFR of 30-59 mL/ minute/1.73m2. Metformin doses should be discontinued in patients with an eGFR less than 30 mL/ minute/1.73m2^1,2,5-8.

In moderate renal impairment (CrCl 30 to 59 ml/min), alogliptin dosages should be reduced to 12.5 mg daily, while in patients with severe renal impairment (CrCl less than 30 ml/min), alogliptin dosages should not exceed 6.25 mg daily^1,2,10.

Linagliptin dosages do not need to be adjusted for renal insufficiency. Patients on linagliptin combination therapy with a CrCl less than 30 ml/min may have increased risk of hypoglycemia and may need more frequent monitoring and/or dose adjustments^1,2,11.

Saxagliptin dosages should be reduced to 2.5 mg once daily in patients with CrCl less than 45 ml/min or in patients prescribed a strong CYP3A4 inhibitor (e.g., ketoconazole)^1,2,12.

Sitagliptin dosages should be adjusted in adult patients with renal insufficiency.  Patients with CrCl 30 – 44 ml/min should receive sitagliptin 50 mg daily, while patients with severe renal insufficiency CrCl less than 30 ml/min or those patients with end stage renal disease requiring hemodialysis or peritoneal dialysis should receive sitagliptin 25 mg daily^1,2,13.

Repaglinide should be initiated at a dose of 0.5 mg before each meal in patients with a CrCl between 20-39 mL/min^1,2,18.

Canagliflozin doses in patients with renal impairment should be reduced to 100 mg daily when the estimated glomerular filtration rate (eGFR) is 30-59 ml/min/1.73 m2 and avoided when eGFR is less than 30 ml/min/1.73 m2. Patients may continue up to 100 mg daily of canagliflozin when eGFR is less than 30 ml/min/1.73 m2 if they have albuminuria greater than 300 mg/day^1,2,19.

Dapagliflozin dosages should be adjusted in patients with renal impairment. For patients with an eGFR of 25-44 ml/min/1.73m2 the maximum dose is 10 mg daily. Initiating dapagliflozin in patients with an eGFR less than 25 ml/min/1.73m2 is not recommended. However, patients may continue therapy if eGFR declines to less than 25 ml/min/1.73m2. Dapagliflozin is contraindicated in patients on dialysis^1,2,20.

Empagliflozin therapy should not be initiated in patients with eGFR less than 30 ml/min/1.73m2 for glycemic control if they do not have established cardiovascular disease or cardiovascular risk factors. Studies in patients with heart failure enrolled patients with an eGFR equal to or above 20 ml/min/1.73m2, and there is insufficient data to recommend use in patients with an eGFR below 20 ml/min/1.73m2. Empagliflozin is contraindicated in patients with an eGFR less than 20 ml/min/1.73m2^1,2,21.

Ertugliflozin therapy is not recommended in patients with an eGFR less than 45 mL/min/1.73m2^1,2,22.

Glimepiride should be initiated at 1 mg daily and slowly titrated in patients with renal impairment^1,2,23.

Glyburide should be avoided in patients with renal impairment. If use is necessary, start at 1.25 mg daily conventional glyburide, 0.75 mg daily for micronized glyburide. All sulfonylurea medications should be initiated with caution and at a reduced starting dose to minimize the risk of hypoglycemic events^1,2,23-27.