ADA 2018 Standards Address Diabetes Drugs With CV Benefit

Miriam E Tucker

December 08, 2017

The American Diabetes Association's annual guidelines for 2018 include new recommendations for use of glucose-lowering drugs with proven cardiovascular benefit in type 2 diabetes, optimization of diabetes care in elderly patients, and glucose screening of high-risk adolescents.

The organization has also chosen to stick with its existing definition of hypertension in diabetes, of 140/90 mm Hg, in contrast to cardiology societies that have recently changed their guidance so that ≥130/80 mm Hg represents "stage 1 hypertension," including in diabetes.

Probably the most anticipated and impactful new recommendation from the ADA calls for use of a glucose-lowering agent with proven cardiovascular benefit — such as the glucagonlike peptide 1 (GLP-1) agonist liraglutide (Victoza Novo Nordisk) — and/or mortality reduction — such as that observed with the sodium glucose cotransporter-2 (SGLT2) inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Lilly) — in type 2 diabetes patients with established atherosclerotic cardiovascular disease (ASCVD) who don't meet glycemic targets with lifestyle modification and metformin.

"We now have drugs that are not only indicated to improve glycemic control but that reduce cardiovascular risk and mortality. So, based on some of the [cardiovascular-outcomes] trials, there are new recommendations for treatment of adults with type 2 diabetes who fail metformin therapy, if there's a background of atherosclerotic cardiovascular disease," the ADA's chief scientific, medical, and mission officer, William T Cefalu, MD, told Medscape Medical News.

A new table outlines the data from recent cardiovascular-outcomes studies, and a new figure details the recommendations based on those (Section 8, page S97, Table 9.4 and page S76, Figure 8.1, respectively).

Another important chart summarizes all drug-specific and patient factors that may affect diabetes treatment and includes the most relevant considerations, such as risk of hypoglycemia, weight effects, kidney effects, and costs for all preferred diabetes medications, in one location to guide the choice of antihyperglycemic agents "as part of patient-provider shared decision-making," notes the ADA (Section 8, page S77, Table 8.1).

"The standards of care are the primary resource for the optimal management of diabetes and include updated guidelines for diabetes diagnosis and for evidence-based prevention of diabetes and diabetes-related complications. We are especially proud of the new recommendations for patients with diabetes and cardiovascular disease," Dr Cefalu noted in an ADA statement, which summarizes the major changes to prior guidance.

The 173 pages of the ADA's 2018 Standards of Medical Care in Diabetes were published online December 8, 2017 in Diabetes Care. The 12-member writing panel was chaired by Rita R Kalyani, MD, of Johns Hopkins School of Medicine, Baltimore, Maryland.

Glucose Screening of Kids, Use of HbA1c, the Elderly, and CGMs

Another major new recommendation calls for screening for prediabetes and type 2 diabetes in children and adolescents who are overweight or obese and who have one or more additional risk factors.

"Clearly, it's different from type 2 in adults. There seems to be a more rapid decrease in beta-cell function," Dr Cefalu noted.

And regarding use of HbA1c for screening, diagnosis, or monitoring of diabetes, there is new information in the standards on limitations of the test in people with hemoglobin variants such as sickle-cell anemia and other conditions affecting red blood cell turnover.

There is also a mention of ethnic differences in the relationship of HbA1c to average blood glucose levels.

Three new recommendations address the importance of individualizing pharmacologic therapy in older adults to reduce hypoglycemia risk, avoid overtreatment, and simplify complex regimens as much as possible while maintaining HbA1c targets.

A chart provides guidance on individualizing targets — ie, <7.5%, <8.0%, or <8.5% — for older adults based on functional status, comorbidities, and life expectancy.

There's also guidance for expanding the use of continuous glucose monitoring (CGM), indicating that it should be employed by all adults aged 18 years and older with type 1 diabetes who don't meet glycemic targets (from the current age of 25 and above), but there is no pediatric recommendation as yet.

And there's information on the availability of a new intermittent ("flash") glucose monitoring device, the FreeStyle Libre (Abbott) recently approved in the US for adult use and the fact that some CGMs (ie, Dexcom G5) are now approved to replace finger-stick testing for making treatment decisions.

No Change in BP Targets; Rather, the ADA Stresses Individualization

Notably, the new ADA standards do not change the association's prior hypertension definition of ≥140/90 recently put forth in a separate set of guidelines.

This contrasts with the recent statement from the American College of Cardiology, the American Heart Association, and other organizations deeming ≥130/80 as "stage 1 hypertension," including specifically for people with diabetes.

The ADA document acknowledges the difference and provides details to support the 140/90 cutoff for people with diabetes.

This includes the ACCORD-BP trial involving 4733 type 2 diabetes patients, in which intensive blood-pressure control targeting systolic <120 did not improve the composite primary cardiovascular end point, and ADVANCE BP with 11,140 type 2 patients, in which the composite end point was improved but blood-pressure level achieved in the intervention group was 136/73.

Other large trials showing benefit for more intensive blood pressure-lowering, including SPRINT, didn't enroll patients with diabetes.

These three studies, plus the HOT trial, are summarized and outlined in a new table, providing support for the existing ADA recommendations that most adults with diabetes and hypertension should have a target blood pressure of <140/90 mm Hg (Section 9, page S88, Table 9.1)

Also new is an algorithm illustrating the recommended antihypertensive treatment approach for such individuals (Section 9, page S90, Figure 9.1).

However, the ADA standards also say "Intensification of antihypertensive therapy to target blood pressures lower than <140/90 mm Hg (eg, <130/80 or <120/80 mm Hg) may be beneficial for selected patients with diabetes such as those with a high risk of cardiovascular disease."

On this topic, Dr Cefalu said: "We were aware of the recommendations from other organizations, and moving forward we will consider all the additional evidence."

He stressed also that the ADA's guidelines advise individualization in blood-pressure management, as in all things. "We recommend individualization of care based on the particular patient and their comorbidities. We specifically discuss how to assess risk holistically and evaluate the whole patient."

The ADA does join the AHA/ACC and other groups in new advice that patients with diabetes and hypertension monitor their blood pressure at home in order to overcome masked or "white-coat" hypertension and improve adherence to medications.

Also new is a recommendation that all pregnant women with preexisting type 1 or type 2 diabetes should consider daily low-dose aspirin starting at the end of the first trimester in order to reduce the risk of preeclampsia.

Standards of the Future Will Be in "Real Time"

Going forward, the ADA standards will be continually revised rather than published all at once at the end of each year.

"We're changing the format, based on the fact that in this day and age so much new evidence accumulates so fast. We're going to a real-time, 'living document' that is event-driven," Dr Cefalu explained.

Thus, the standards will be changed right away if a new drug is approved, gains a new indication, or any other major changes occur that represent a significant shift in clinical practice.

A new standards app will be launched in February 2018. But for those who prefer the old-fashioned way, a hard copy will still come out in Diabetes Care every January.

Dr Cefalu is an employee of the American Diabetes Association. He has no further relevant financial relationships. Dr Kalyani has no relevant financial relationships. Disclosures for the coauthors are listed in the paper.

Diabetes Care. Published online December 8, 2017. Article 

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