Overview of Data Concerning the Safe Use of Antihyperglycemic Medications in Type 2 Diabetes Mellitus and Chronic Kidney Disease

It can be a challenge to manage glycemic control in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), due to both patient and medication issues. Although most antihyperglycemic medications can be used in mild kidney disease, many medications are either not advised or require dose adjustments in more advanced CKD. This review summarizes product label information, pharmacokinetic and clinical studies, and clinical guidelines relevant to use of antihyperglycemic medications in CKD. Product labels and guidelines from North America and Europe, as well as pharmacokinetic and clinical studies of diabetes medication use in CKD were identified through Medline and PubMed searches, up to February 2015. Available data are summarized and correlations between treatment recommendations and available research are discussed, as are glycemic targets for patients with CKD. Newer medications have significantly more data available than older medications regarding use in CKD, although larger clinical studies are still lacking for some drugs. As CKD advances, dose adjustment is needed for many medications [numerous dipeptidyl peptidase-4 inhibitors, some insulins, sodium glucose co-transporter 2 (SGLT2) inhibitors], although not for others (thiazolidinediones, meglitinides). Some medications are not recommended for use in more advanced CKD (metformin, SGLT2 inhibitors, some glucagon-like protein-1 receptor agonists) for safety or efficacy reasons. There is not always good alignment between label recommendations, pharmacokinetic or clinical studies, and guideline recommendations for use of these drugs in CKD. In particular, controversy remains about the use of metformin in moderate CKD and appropriate use of liraglutide and sulfonylureas in advanced CKD. Considerable variability exists with respect to recommendations and clinical data for the many antihyperglycemic drugs used in patients with T2DM and CKD. Eli Lilly and Company.