Personalize Diabetes Therapy, New EASD-ADA Guidelines Stress

BERLIN — New consensus guidelines on patient-centered management of type 2 diabetes have now been published for clinicians in Europe and the United States.

The final version of the document, "Management of Hyperglycaemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)," was presented October 5 here at the European Association for the Study of Diabetes (EASD) 2018 Annual Meeting and simultaneously published in both Diabetologia and Diabetes Care.

A draft version was presented in June 2018 at the ADA 78th Annual Scientific Sessions.

Based on more than 800 comments received since that meeting, the final version includes a few noteworthy changes and several minor ones.

Put Patient at the Center of the Treatment Decision

Unchanged from June but in a major shift since the last ADA-EASD consensus report from 2015, this one recommends that the choice of second-line glucose-lowering agents after metformin be driven by new evidence from cardiovascular outcomes trials and by areas of medical need, including weight reduction and avoidance of hypoglycemia. And for injectables, it advises that glucagon-like peptide (GLP)-1 agonists are preferred over insulin.

The document also focuses in detail on lifestyle interventions, with emphasis on weight loss and obesity management, including metabolic surgery. In terms of choice of diet, the new guidelines recognize "there is no single ratio of carbohydrate, proteins, and fat intake that is optimal for every person with type 2 diabetes." However, they also acknowledge that following a Mediterranean-type diet generally seems to result in modest weight loss and improved glycemic control.

And "if a patient wishes to aim for remission of type 2 diabetes, particularly within 6 years of diagnosis, evidence-based weight management programs are often successful," they note. The most effective nonsurgical strategies for weight reduction involve food substitution (ie, meal replacement; 825- to 853-kcal/day formula diet for 3 to 5 months), followed by gradual reintroduction of food and intensive counseling.

Overall, the guidelines strongly emphasizes that all treatment decisions be made in collaboration with the patient, experts said at EASD.

"You can't simply look at all the science... The patient has to be at the center of all of this. You need key patient characteristics, you consider the factors, you share the decision-making, agree on management, and you go round and round…because our science is held by human hands," commented incoming EASD resident David R. Matthews, MD, professor of diabetes and chair of the Oxford Centre for Diabetes, United Kingdom. Matthews co-chaired the two previous EASD-ADA consensus documents but wasn't involved in this new one.

Indeed, said report coauthor Chantal Mathieu, MD, PhD, professor of medicine at the Katholieke Universiteit Leuven, Belgium, and chair of endocrinology at the University Hospital Gasthuisberg Leuven, "The patient is at the center of everything…. We should assess key patient characteristics and consider specific factors that will impact choice of treatment, and then come to shared decision-making to create a management plan."

"What is important is that the patient agrees on this plan, and that this plan is revised over and over and over again as the life of the patient progresses," she stressed.

CKD Now Included for Assessment; Cost Also an Issue to Consider

As announced in June, the guidelines reconfirm the choice of metformin as a first-line treatment for most patients with type 2 diabetes. If a second glucose-lowering drug is needed, the decision should first be based on whether the patient has atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), and/or heart failure (HF).

For those with ASCVD, a GLP-1 agonist or an sodium-glucose cotransporter 2 (SGLT2) inhibitor are recommended. However, for patients with HF or CKD with or without ASCVD, an SGLT2 inhibitor is preferred.

And in general, specific agents with proven benefit are preferred. These would include the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim), based on the EMPA-REG OUTCOME trial and the GLP-1 agonist liraglutide (Victoza, Novo Nordisk) based on the LEADER trial.

The inclusion of CKD in this initial assessment — rather than farther down in the algorithm — is a change from the draft version of the document presented at the ADA meeting.

For patients without ASCVD, HF, or CKD, the choice of second-line drug should be based on three factors: compelling need to avoid hypoglycemia, compelling need to minimize weight gain or promote weight loss, and cost.

For the avoidance of hypoglycemia, the recommendation gives equal weight to SGLT2 inhibitors, GLP-1 agonists, dipeptidyl peptidase-4 inhibitors, and thiazolidinediones. For weight concern, either an SGLT2 inhibitor or a GLP-1 agonist with good efficacy for weight loss is advised.

But if cost is a major issue — also featured more prominently in the algorithm now than it had been in the draft — sulfonylureas or TZDs at the lowest effective dose are offered as options, along with thorough patient education about minimizing the risks for side effects such as hypoglycemia and weight gain.

And in an addition to the draft, the final version includes advice for patients with ASCVD or CKD who are at their recommended hemoglobin A1c target but are not using an SGLT2 inhibitor or GLP-1 agonist with proven cardiovascular benefit.

In such cases, the document offers three options: (1) If the patient is already receiving dual or multiple therapy, consider switching one of the agents, (2) consider lowering the patient's individualized hemoglobin A1c target and then introducing the SGLT2 inhibitor or GLP-1 agonist, or (3) reassess the hemoglobin A1c at 3-month intervals and add the SGLT2 inhibitor or GLP-1 agonist if the A1c rises above target.

Other changes from the draft include the addition of a blue box reminder about avoiding clinical inertia posted prominently at the top of each graphic, and consideration of metabolic surgery for patients with body mass index of 30 to 35 kg/m².

Matthews commented: "There is a balancing of risk, but the reality is that you have to think extremely hard with your patients about what those balances are. This is a complex thing to do, and we encourage you to do this…. What you have here is a wonderful handbook to guide you in your decision-making."

Matthews is on advisory boards for, receives research support from, or is a speaker for Novo Nordisk, GlaxoSmithKline, Novartis, Eli Lilly, Sanofi Aventis, Janssen, and Servier. Mathieu has received grants and/or personal fees from Novo Nordisk, Sanofi, Merck Sharp & Dohme, Eli Lilly, Novartis, Bristol-Myers Squibb, AstraZeneca, Boehringer Ingelheim, Hanmi Pharmaceuticals, Roche Diagnostics, Medtronic, Intrexon, Abbott, and UCB.

European Association for the Study of Diabetes (EASD) 2018 Annual Meeting. Presented October 5, 2018.

Diabetologia. Published online October 5, 2018. Abstract

Diabetes Care. Published online October 4, 2018. Abstract

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