AACE Publishes Latest 'Cookbook' for Diabetes Management

Miriam E Tucker

January 15, 2016

An updated algorithm for type 2 diabetes management from the American Association of Clinical Endocrinologists (AACE) combines colorful graphics with text into one document, includes new sections on lifestyle therapy and overall guiding principles, and incorporates all relevant medications available in the United States as of 2015.

The document is published on the AACE website and in the January issue of Endocrine Practice.

As in the past, it addresses management of obesity, prediabetes, dyslipidemia, and hypertension in addition to glycemic control.

As a whole, this "continues to be a very important clinical and practical cookbook for clinicians, particularly primary-care providers, but can also help endocrinologists. Clinicians should find it very easy to use and very relevant," statement coauthor Yehuda Handelsman, MD, medical director and principal investigator, Metabolic Institute of America, Tarzana, California, told Medscape Medical News.

Overall, there aren't major changes from 2015 in therapeutic recommendations in the new 2016 "Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm." Rather, there are refinements based on new data.

Efficacy and Safety Deemed More Important Than Cost

This year, the text is accompanied by nine separate color-coded graphic algorithms for lifestyle therapy, overweight/obesity, prediabetes, glycemic control, insulin therapy, cardiovascular risk-factor modification, medication profiles, and guiding principles. (In 2015 the text and the graphics were published at different times.)

The document incorporates all medications approved by the Food and Drug Administration through December 2015 for managing hyperglycemia, weight, blood pressure, and dyslipidemia.

It begins with a new list of "founding principles," including a focus on "multifaceted, ongoing" lifestyle optimization, individualization of both therapeutic options and HbA1c targets (although the basic recommendation on the latter remains 6.5% or lower for patients who can achieve it safely), and minimization of hypoglycemia and weight gain.

The document also calls for prioritization of safety and efficacy over medication cost, noting that "the initial acquisition of cost of medications is only a part of the total cost of care."

Lifestyle therapy (previously "modification") is now given its own section, focusing on nutrition counseling and education, physical activity, adequate rest, and behavioral support.

"We [have been] saying that lifestyle is important, so now we're focusing on it specifically," Dr Handelsman noted.

Medication Hierarchy: What Follows Metformin?

In the glycemic-control algorithm, metformin is listed as first-line monotherapy (for those with entry HbA1c below 7.5%), but several other options are given as alternatives, including (in order): glucagonlike peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinediones (TZDs), alpha glucosidase inhibitors, and sulfonylureas/glinides.

Both TZDs and sulfonylureas are listed in yellow, indicating that they should be used with caution.

Similarly, dual therapy options (for patients with HbA1c 7.5% or greater) include those agents, along with colesevelam (Welchol, Daiichi Sankyo), quick-release bromocriptine (Cycloset, VeroScience), and basal insulin, also presented in yellow.

These recommendations remain essentially the same as last year.

Dr Handelsman said that some people have questioned why DPP-4 inhibitors are still ranked above TZDs, now that the restrictions on rosiglitazone have been lifted. The reason, he said, is that "TZDs may be slightly more potent and don't cause hypoglycemia but can cause fluid overload and weight gain."

In contrast, while DPP-4 inhibitors may be less potent, "at the end of the day, DPP-4s have a clean side-effect profile."

Others have questioned why SGLT2 inhibitors were placed above DPP-4 inhibitors. There, the panel was swayed by several studies showing that the SGLT2 inhibitors are more potent and also have the potential benefit of weight loss and blood-pressure reduction. While the agents have been linked to reports of diabetic ketoacidosis (DKA), AACE/ACE recently held a conference in which experts concluded that DKA is rare and no labeling changes were necessary.

The text of the document also discusses recent trials, including the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) study, which found a significant cardiovascular and all-cause mortality reduction with one particular SGLT-2 inhibitor, empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) in type 2 diabetes patients with established cardiovascular disease.

However, the panel did not make any changes to last year's algorithm based on EMPA-REG.

Dr Handelsman pointed out that EMPA-REG was designed to look at CV end points rather than glucose-lowering, and the study subjects were not representative of the entire type 2 diabetes population.

"It was a CV safety trial....The data are on a very specific group of patients with an incredibly high CV risk....The majority of patients aren't in this specific group."

Keeping It Simple

Other than metformin, the document lists only classes of drugs and not individual agents within those classes.

This was done for simplicity's sake, Dr Handelsman said, noting that such differentiation would actually have been more useful for the GLP-1 drugs than for the SGLT2 inhibitors or other agents, given the different properties of the longer-acting vs the once-daily GLP-1 receptor agonists. "The side-effect profile differs, but [listing them separately] would make the document very complicated."

Also new this year is the inclusion of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the lipid section and the specification of two options for initiating prandial insulin — either limiting to just the largest meal of the day and subsequently adding to the others if necessary or adding to all three meals all at once.

"The new part is allowing for both approaches," he said.

The document and algorithm will be revised again in a year, Dr Handelsman noted.

Dr Handelsman reports that he received research grant support from Amgen, Boehringer Ingelheim, Grifols, Gilead, Himni, Intarcia, Lexicon, Merck, Novo Nordisk, Sanofi, and Takeda. He is a consultant for Amarin, Amgen, Dia Deux, Eisai, Gilead, Halozyme, LipoScience, Merck, Novo Nordisk, Sanofi, Vivus, and Janssen. He is a speaker for Amarin, Amgen, AstraZeneca, Boehringer Ingelheim/Lily, Janssen, Novo Nordisk, Vivus, and Regeneron. Disclosures for the coauthors are listed in the article.

Endocr Pract. 2016;22:84-113. Article, Algorithm


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.