PracticeUpdate Diabetes Best of 2018

TOP STORIES 2018 8

New ADA-EASD Type 2 Diabetes Treatment Guidelines By Silvio E. Inzucchi MD

I have selected the new ADA-EASD type 2 diabe- tes treatment guidelines as my Story of the Year. 1 Over the past 2 decades, a multitude of glu- cose-lowering therapies have become available for type 2 diabetes. Because diabetes is a progressive disease, several medications are often necessary in combination to adequately control blood glucose concentrations and HbA1c. A substantial number of patients eventually require insulin injections, often taken several times per day. Primary care clinicians – who probably treat 90% of patients with diabetes in the US – often seek out guidance from authori- tative sources to assist in their management of this increasingly complex disease. Sets of recommendations from the American Diabetes Association (ADA) and the European Asso- ciation for the Study of Diabetes (EASD) began to be published in 2006. 2 That consensus statement recommended initial therapy with lifestyle change and metformin. If additional glucose-lowering was needed to achieve the HbA1c target of <7%, three options were available: a sulfonylurea, a thiazolidin- edione (TZD), and basal insulin. If triple therapy was required, options not already on board could be added (eg, metformin + sulfonylurea + TZD). Some patients would eventually transition to multiple daily insulin injections. A 2008 update incorporated a new drug category: the GLP-1 receptor agonists. 3 That somewhat controversial algorithm distinguished the choices after metformin between those that were “well-validated’ (sulfonylureas, basal insulin) from those that were “less well-validated” (the TZD pio- glitazone, GLP-1 receptor agonists). In 2012, the ADA-EASD published their first posi- tion statement on this topic. 4 In contrast to prior consensus statements, this algorithm was formally endorsed by the professional practice committees of both organizations and approved by their executive committees. The emphasis here was on patient-cen- tered care. Its first section reviewed glycemic targets and how they might be determined for each patient. In most patients, the goal was 7% or less, but lower levels were felt to be reasonable in younger and healthier patients and looser targets advisable in older and sicker individuals. Its second section focused on therapeutic strategies, with metformin remaining as first-line therapy. After metformin, one of six additional drug classes could be considered (sulfonylureas, TZDs, DPP-4 inhibitors, GLP-1 recep- tor agonists, or basal insulin). Given the lack of comparative efficacy data beyond glucose control

and adverse events, the precise choice was left to the clinician – to be individualized to each patient. Some adverse effects of therapy were considered to be key: weight gain, hypoglycemia, edema, and gastrointestinal distress. An update was published in 2015. 5 This included the newer class at that time, the SGLT2 inhibitors, and also described the emerging strategy of a GLP-1 receptor agonist in combination with basal insulin (in lieu of multiple injections of rap- id-acting insulin before meals). Since 2015, several clinical trials (EMPA-REG OUT- COME, CANVAS, LEADER, SUSTAIN-6, and, just recently, HARMONY Outcomes and DECLARE) have demonstrated clear cardiovascular (CV) benefits of specific glucose-lowering drugs within the SGLT2 inhibitor (empagliflozin, canagliflozin) and GLP-1 receptor agonist (liraglutide, semaglutide) classes. In some trials, this included a CV mortality advantage. Moreover, the SGLT2 inhibitor trials have demon- strated a benefit in the prevention of heart failure (HF) hospitalizations as well as in the progression of chronic kidney disease (CKD). So, there was a clear need to develop a new set of recommendations to address this new evidence and how it might be incorporated into the treatment paradigm of type 2 diabetes. The long-anticipated 2018 ADA-EASD guidelines (the Consensus Report) were published in October and simultaneously presented by the writing group at the EASD meeting in Berlin. 1 These are in part sim- ilar to prior versions in that they begin with lifestyle

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