Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control

Betônico, Carolina C.R.; Titan, Silvia M.O.; Correa-Giannella, Maria Lúcia C.; Nery, Márcia; Queiroz, Márcia

doi:10.6061/clinics/2016(01)08

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REVIEW • Clinics 71 (1) • Jan 2016 • https://doi.org/10.6061/clinics/2016(01)08 copy

Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control

Authorship SCIMAGO INSTITUTIONS RANKINGS

The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population.

Type 2 Diabetes Mellitus; Chronic Kidney Disease, Diabetic Kidney Disease; Renal Failure; Diabetes Treatment; Oral Antidiabetic Drugs

Class and Medication	Dose Adjustment Based on eGFR
Biguanide
Metformin	USA prescribing information: contraindication for men with serum creatinine ≥1.5 mg/dL and women with serum creatinine ≥1.4 mg/dL UK guideline allows metformin in patients with eGFR >30 mL/min/1.73 m²KDIGO recommends metformin in patients with eGFR >45 mL/min/1.73 m²
Sulfonylureas
Glipizide	No dose adjustment required
Glimepiride	Initiate conservatively at 1 mg daily Avoid use if eGFR <60 mL/min/1.73 m²
Gliclazide	Reduce dose if eGFR <30 mL/min/1.73 m². Not recommended if eGFR <15 mL/min/1.73 m²
Glyburide or glibenclamide	Avoid use in patients with eGFR <60 mL/min/1.73 m²
Meglitinides
Repaglinide	Initial dose of 0.5 mg before meals when eGFR <30 mL/min/1.73 m²
Nateglinide	Caution when used with eGFR <30 mL/min/1.73 m². Initiate with 60 mg before meals
a-Glucosidase inhibitors
Acarbose	Avoid if eGFR <30 mL/min/1.73 m²
Miglitol	Avoid if eGFR <30 mL/min/1.73 m²
TZDs
Pioglitazone	No dose adjustment required. Use with caution in patients with CKD and hypervolemia
GLP-1 receptor agonists
Exenatide	Avoid if eGFR <30 mL/min/1.73 m². When eGFR between 30 and 50 mL/min/1.73 m² dose should not exceed 5 mcg
Lixisenatide	Avoid if eGFR <50 mL/min/1.73 m²
Liraglutide	Avoid if eGFR <60 mL/min/1.73 m²
DPP-4 inhibitors	Sitagliptin and saxagliptin dose adjustment required based on eGFR
Sitagliptin	100 mg daily if eGFR <50 mL/min/1.73 m²
	50 mg daily if eGFR 30-50 mL/min/1.73 m²
	25 mg daily if eGFR <30 mL/min/1.73 m²
Saxagliptin	5 mg daily if eGFR <50 mL/min/1.73 m²
	2.5 mg daily if eGFR <50 mL/min/1.73 m²
Alogliptin	1.25 mg per day when eGFR 30-60 mL/min/1.73 m², and for those patients with eGFR <30 mL/min/1.73 m² or hemodialysis, the dose should not exceed 6.25 mg/day
Linagliptin	No dose adjustment required
Linagliptin	SGLT2 inhibitors
Canagliflozin	No dose adjustment required if eGFR <60 mL/min/1.73 m²
	100 mg daily if eGFR 45-59 mL/min/1.73 m²
Dapagliflozin	Avoid use if eGFR <60 mL/min/1.73 m², and discontinue use if eGFR <45 mL/min/1.73 m²

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[1] Betônico CR conceived and designed the study and was responsible for the data acquisition. Titan SM, Correa-Giannela ML and Nery M were responsible for the data acquisition. Queiroz MS was responsible for the manuscript drafting, critical revision of the manuscript for important intellectual content and approval of the final version of the manuscript. All authors read and approved the final version of the manuscript.