PracticeUpdate Diabetes March 2019

EXPERT OPINION 22

Management of Hyperglycemia in Type 2 Diabetes, 2018: Consensus Report by ADA and EASD By Silvio E. Inzucchi MD

T he ADA and EASD, the two leading professional diabetes organizations, have just published their updated guidelines for glucose-lowering therapy for patients with type 2 diabetes. The writing group has done a formidable job in updating the latest guidelines, which were published in 2015. That seems to be such a long time ago, given the major developments in this area over just the past 3 years. Prior to 2015, there were few large, long- term studies looking at the impact of diabetes medications on the major risks from this disease, namely cardiovascular complications. We now have several studies involving specific SGLT2 inhibitors and GLP-1 receptor agonists pointing to clear CV benefits, at least in high-risk patients. So, one of the major changes in the guidelines is that, after metformin monotherapy, the clinician is advised to determine whether atherosclerotic CV disease (D) is present – if it is, and if additional glu- cose lowering is needed, then one of these two drug classes should be added to metformin. Of course, the choice of drug should be based on the results of clinical trials, favoring those agents proven to have benefits. In addition, the writing group recommends that if heart failure (HF) or chronic kidney disease (CKD) dominate the clinical picture, an SGLT2 inhib- itor would be the favored choice. Of course, kidney function should be sufficient to allow for SGLT2 inhib- itor therapy because these agents are not approved once the eGFR is <45 (some endocrinologists use them cautiously down to an eGFR of 30). The other big change is that the guidelines now advise that, for most patients who are transition- ing to injectable therapy, a GLP-1 receptor agonist

is preferred over insulin. This recommendation is based on multiple studies showing as good glyce- mic control, with less hypoglycemia and weight loss instead of weight gain. I found the guidelines comprehensive and informative, and, for themost part, highly evidence-based. Thewrit- ing committee may have pushed the envelope a bit in their recommendations regarding SGLT2 inhibitors in HF andCKDpatients, since those benefits have not yet been demonstrated as primary outcomes in dedicated HF and CKD trials. (One CKD study, CREEDENCE, involving canagliflozin, was stopped early due to ben- efit, but the details are not yet published.) They actually drifted a bit from the evidence in recommending GLP-1 receptor agonists after SGLT2 inhibitors (or in lieu of SGLT2 inhibitors if there were contraindications) in HF/CKD patients. There is actually no evidence that GLP-1 receptor agonists help HF outcomes, and their effect on CKD is solely to reduce albuminuria – not the progression of renal dysfunction per se. Finally, I thought pioglitazone was unfairly relegated to a niche role (mainly when costs are a big concern, since it is generic). Yet, this TZD, in spite of its known side effects (weight gain, edema, fractures, etc) has been shown to reduce adverse CV outcomes in two trials, PROactive and IRIS. So, I was a little disappointed in its positioning. Irrespective of these relatively minor criticisms, the writing committee should be congratulated on a job well done. These guidelines will serve us for years with a solid set of recommendations. This commentary is based upon the article Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) by Davies et al. Reference 1. Davies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018 Oct 04;[EPub Ahead of Print]. www.practiceupdate.com/c/74407

" … one of the major changes in the guidelines is that, after metformin monotherapy, the clinician is advised to determine whether atherosclerotic CV disease (D) is present… "

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