A guideline developed by a workgroup of Kidney Disease: Improving Global Outcomes (KDIGO) offered 12 recommendations and 48 practice points for clinicians caring for patients with diabetes and chronic kidney disease (CKD). The recommendations touch on comprehensive care, glycemic monitoring and targets, lifestyle interventions, antihyperglycemic therapies, and approaches to management.
The guideline was published online in October 2020 and covered in the November 2020 ACP Diabetes Monthly. The following commentary by Thomas Karagiannis, MD, MSc, PhD, Apostolos Tsapas, MD, PhD, MSc(Oxon), and Eleni Bekiari, MD, MSc, PhD, was published in the ACP Journal Club section of Annals of Internal Medicine on March 2.
The KDIGO guidelines highlight the importance of treating patients who have diabetes, hypertension, and albuminuria with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. Among glucose-lowering drugs, metformin and sodium–glucose cotransporter-2 (SGLT2) inhibitors are recommended as first-line treatment, whereas glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are second-line options for patients with type 2 diabetes mellitus (T2DM) and CKD. The recommendation for metformin is based on its established efficacy and safety profile (even in patients with an estimated glomerular filtration rate [eGFR] as low as 30 mL/min/1.73 m2), low cost, and potential cardioprotective benefits. The recommendations for SGLT2 inhibitors and GLP-1 RAs are supported by meta-analyses of cardiovascular outcomes trials that included patients with CKD and a dedicated kidney outcome trial for canagliflozin in patients with T2DM and CKD.
Despite inherent limitations of subgroup analyses, the consistency of findings for patients with T2DM and CKD across trials suggests that chance is an unlikely explanation for the observed beneficial cardiovascular and kidney effects of SGLT2 inhibitors and long-acting GLP-1 RAs. The credibility of the subgroup meta-analyses based on kidney disease is enhanced by the fact that the analyses synthesized within-trial subgroup differences from well-designed and executed trials. The evidence is particularly strong for canagliflozin because it is also based on data from a dedicated kidney outcome trial. Of note, a kidney outcome trial for dapagliflozin has been recently published, whereas studies are ongoing for empagliflozin and semaglutide.
The KDIGO Work Group is committed to update its recommendations with data from these ongoing trials and from cardiovascular outcomes trials for ertugliflozin, finerenone, and sotagliflozin. This underscores the value of a living systematic review process to ensure that guidelines keep up with emerging evidence as soon as it becomes available.