eGFR ‘cut-offs’ for glucose lowering therapies Last updated 23/04/2019 CKD Stage 1 (>90) CKD Stage 2 (60-89) CKD Stage 3 (30-59) CKD Stage 4 (15-29) CKD Stage 5 (<15) Glimepiride No adjustment Avoid use Other OADs Repaglinide No adjustment Pioglitazone* No adjustment <4 Cr/Cl Sitagliptin No adjustment Lower dosages are recommended (see SmPC) Saxagliptin No adjustment 2.5 mg/day Avoid use DPP-4i Vildagliptin No adjustment 50 mg/day (Cr/Cl <50) eGFR ‘cut-offs’ for glucose lowering therapies Alogliptin No adjustment 12.5 mg/day 6.25 mg/day Linagliptin No adjustment Dapagliflozin No adjustment† Avoid use if eGFR < 45 ml/min Empagliflozin No adjustment† 10 mg/day† Avoid use if eGFR < 45 ml/min SGLT-2 Canagliflozin No adjustment† 100 mg/day† Avoid use if eGFR < 45 ml/min Ertugliflozin No adjustment Avoid use if eGFR < 45 ml/min Exenatide BID No adjustment Careful use Avoid use Exenatide OW No adjustment Avoid use (Cr Cl < 50) Renal impairment precludes use of several glucose-lowering medications or requires cautious dose reduction and increased monitoring2 Typically, drugs and active drug metabolites for which the kidney represents the major route of elimination (via glomerular excretion, tubular secretion or both) accumulate as kidney function is impaired3 For these drugs, a dose adjustment or an extended dose interval is usually needed in chronic kidney disease (CKD) patients in order to keep an optimal safety/efficacy profile3 Reducing the dose without altering dosing frequency has a higher risk of overdosing the drug (due to progressive accumulation), but assures continuous coverage3 References Summary of Product Characteristics. Available at: www.medicines.org.uk/EMC/medicine/ [Accessed March 2015]. Glimepiride SmPC. Available at: https://www.medicines.org.uk/emc/medicine/25845 Prandin® SmPC. Available at: https://www.medicines.org.uk/emc/medicine/18980 Actos® SmPC. Available at: https://www.medicines.org.uk/emc/medicine/4236 Januvia® SmPC. Available at: https://www.medicines.org.uk/emc/medicine/19609 Vipidia® SmPC. Available at: https://www.medicines.org.uk/emc/medicine/28513 Trajenta® SmPC. Available at: https://www.medicines.org.uk/emc/medicine/25000 Forxiga® SmPC. Available at: https://www.medicines.org.uk/emc/medicine/27188 Invokana® SmPC. Available at: https://www.medicines.org.uk/emc/medicine/28401 Byetta® SmPC. Available at: https://www.medicines.org.uk/emc/medicine/19257 Bydureon® SmPC. Available at: https://www.medicines.org.uk/emc/medicine/29798 Lyxumia® SmPC. Available at: https://www.medicines.org.uk/emc/medicine/27406 Trulicity® SmPC. Available at: https://www.medicines.org.uk/emc/medicine/29747 Victoza® SmPC. Available at: https://www.medicines.org.uk/emc/medicine/21986 Bailey CJ and Day C. Diabetes therapies in renal impairment. Br J Diabetes Vasc Dis 2012;12:167-171. Arnouts P, Bolignano D, Nistor I, et al. Glucose-lowering drugs in patients with chronic kidney disease: a narrative review on pharmacokinetic properties Nephrol Dial Transplant 2013;0:1–18. Lixisenatide No adjustment Careful use Avoid use GLP-1 RA Albiglutide** No adjustment Avoid use Dulaglutide No adjustment Avoid use Liraglutide No adjustment Avoid use Semaglutide No adjustment Avoid use *pioglitazone should be avoided in dialysed patients and No dose adjustment is necessary in patients with impaired renal function (creatinine clearance > 4 ml/min); †Additional licence precautions; **Not launched – Final licence precautions not confirmed. CKD, chronic kidney disease; DPP-4i, dipeptidyl peptidase-4 inhibitor; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide-1 receptor agonist; OADs, oral antidiabetics; SGLT-2, sodium glucose co-transporter-2. Indicated Restrictions apply Contraindicated Data derived from respective drug SmPCs. Available at: www.medicines.org.uk/EMC/medicine/ Last reviewed 23/04/2019