Saxagliptin plus metformin  combination in patients with type 2 diabetes and renal impairment.
BACKGROUND
A metformin plus saxagliptin fixed-dose combination is now proposed to clinicians. Furthermore, saxagliptin's license was recently extended to include diabetic patients with moderate or severe renal impairment (RI). However, metformin is still contraindicated in patients with RI.


METHODS
This review analyses the pro and contra of using a combination of saxagliptin and metformin (separately or as a fixed-dose combination) in type 2 diabetic patients with moderate or severe RI. An extensive literature search of all pharmacokinetic data and efficacy/safety profile of metformin and saxagliptin in subjects with RI was performed.


CONCLUSIONS
Since both metformin and saxagliptin are excreted via the kidney, dose adjustment is required in case of moderate-to-severe RI (half dose of saxagliptin). However, major discrepancies exist between guidelines (metformin excluded in case of RI because of the risk of lactic acidosis) and real life (metformin widely prescribed in patients with some degree of RI). Physicians should weigh the benefit/risk ratio carefully before deciding to prescribe or withdraw the combination metformin plus saxagliptin in patients with stable RI. A redefinition of contraindications to metformin will enable more physicians to prescribe within guidelines and to administer saxagliptin combined with metformin in more patients who clearly may benefit from this combination.
University of Liège, Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Sart Tilman (B35), B-4000 Liege 1, Belgium. andre.scheen @ chu.ulg.ac.be
André J
AJ
Scheen
D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D004151:Dipeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018579:Patient Selection; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D008687:Metformin; C502994:saxagliptin; D000218:Adamantane