Glycemic control of type 2 diabetes mellitus across stages of renal impairment: information for primary care providers

Chronic kidney disease (CKD) is a frequent complication of type 2 diabetes mellitus (T2DM) and elevates individuals' risk for cardiovascular disease, the leading cause of morbidity and mortality in T2DM. Achieving and maintaining tight glycemic control is key to preventing development or progression of CKD; however, improving glycemic control may be limited by effects of renal impairment on the efficacy and safety of T2DM treatments, necessitating dosing adjustments and careful evaluation of contraindications. Understanding the treatment considerations specific to each class of T2DM medication is important in individualizing therapy and improving glycemic, renal, and cardiovascular outcomes. Traditional glucose-lowering treatments include insulin, metformin, sulfonylureas, meglitinides, and thiazolidinediones. Each of these agents exhibits altered pharmacokinetics in patients with renal impairment except for the thiazolidinediones, which are metabolized by the liver and do not accumulate appreciably in patients with renal impairment. Newer glucose-lowering treatments include GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 inhibitors. Of these, only the DPP-4 inhibitor linagliptin can be used across all stages of renal impairment without dosing restrictions or concerns regarding dose escalation, and all SGLT2 inhibitors are contraindicated when eGFR <45mL/min/1.73m(2). Several of the newer treatments have also been investigated for effects on renal and cardiovascular outcomes, demonstrating potential benefits of the GLP-1 agonists liraglutide and semaglutide, as well as the SGLT2 inhibitors canagliflozin and empagliflozin, in reducing risk for some adverse renal and cardiovascular events. In addition, some DPP-4 inhibitors have been shown to reduce albuminuria, an indicator of glomerular dysfunction. Consideration of this information is useful in informing optimal management strategies for patients with T2DM and concomitant CKD. More clinical data from future and ongoing clinical trials, including data regarding potential renal and cardiovascular benefits, will be important in clarifying the safety and efficacy profiles of each of these agents in patients with CKD.