Management of Hyperglycemia in Type 2 Diabetes: ADA/EASD Consensus Report

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). Diabetologia 2018;Oct 5:[Epub ahead of print].

The following are key points to remember from the 2018 consensus report on the management of hyperglycemia in type 2 diabetes, written by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD):

  1. This outstanding new guideline for managing hyperglycemia updates the clinical approach that includes the novel new agents that effectively lower atherosclerotic cardiovascular disease (ASCVD) major events and several ASCVD risk factors. It is a must read for all physician and nonphysician providers caring for diabetes and its complications. The key points will be limited to patients with ASCVD, chronic kidney disease (CKD), and chronic heart failure (CHF) and will exclude severe hyperglycemia.
  2. The recommendations are not applicable to monogenic diabetes (MODY [Maturity Onset Diabetes of the Young, most commonly caused by mutations in the HNF1A gene or the GCK gene]), type 1 diabetes, secondary diabetes, or children.
  3. Amongst the fundamental aspects of type 2 diabetes care are establishing goals to prevent complications and optimize quality of life with lifestyle management, including medical nutrition therapy (MNT), physical activity, weight loss, counseling for smoking cessation, and psychological support, often delivered in the context of diabetes self-management education and support (DSMES). The management plan should be SMART: Specific, Measurable, Achievable, Realistic, and Time-limited.
  4. Good glycemic management yields substantial and enduring reductions in onset and progression of microvascular complications with the greatest absolute risk reduction in those with poor control with a more modest benefit with maximal reduction to near normal. A reasonable hemoglobin A1c (HbA1c) target for most adults with life expectancy to see microvascular benefits (generally ~10 years) is about ≤7%. Treatment targets should be individualized based on patient preferences, costs, and goals, risk of adverse effects of therapy (e.g., hypoglycemia in coronary artery disease, and weight gain) and patient characteristics, including frailty and comorbid conditions.
  5. Diabetes confers substantial independent ASCVD risk, and most people with type 2 diabetes have additional risk factors such as hypertension, dyslipidemia, obesity, physical inactivity, CKD, and smoking. Numerous studies have demonstrated the benefits of controlling modifiable ASCVD risk factors in diabetes including reductions in ASCVD events and death when multiple ASCVD risk factors are addressed simultaneously.
  6. Several new products within two drug classes including a sodium-glucose co-transporter-2 (SGLT2) inhibitor and glucagon-like peptide-1 (GLP-1) receptor agonists improve CV outcomes as well as heart failure and progression of CKD. Importantly, within each drug class, the results have been heterogenous. Patients with ASCVD and diabetes were studied in the EMPA-REG OUTCOME trial, which compared the SGLT2 inhibitor empagliflozin to placebo in addition to standard medical treatment for diabetes. The trial demonstrated that empagliflozin significantly lowered the risk of CV mortality, CHF hospitalization, and all-cause mortality with a very modest reduction in HbA1c. The same benefits have not been demonstrated by other drugs in the same class. While the SGLT2 inhibitors may reduce the progression of CKD, they should not be used with more than mild CKD (e.g., avoid with estimated glomerular filtration rate [eGFR] <45 ml/min/1.73 m2).
  7. Among GLP-1 receptor agonists evaluated in ASCVD, liraglutide demonstrated an absolute risk reduction of 1.9% with a hazard ratio of 0.87 (95% confidence interval, 0.78-0.97; p = 0.01 for superiority) for the primary composite outcome of CV death, nonfatal myocardial infarction, and nonfatal stroke (major adverse cardiac events compared with placebo) and CHF. Several other GLP-1 receptor agonists have been evaluated that provide CV benefits, but taken together, the benefit is strongest with liraglutide.
  8. First-line treatment for glucose lowering in type 2 diabetes in ASCVD is lifestyle intervention with diet and exercise, and metformin is the drug of first choice. If patients have historic or recent evidence for ASCVD, SGLT2 inhibitors or GLP-1 receptor agonists with proven cardiovascular benefit are recommended as an early part of glycemic management. If HbA1c remains above target, further intensification in ASCVD can be the addition of the other class with proven CVD benefit, a dipeptidyl peptidase-4 (DPP-4) inhibitor if not on GLP-1 receptor agonist.
  9. If CHF predominates with adequate eGFR, use a SGLT2 inhibitor with evidence of reducing CHF, or a GLP-1 receptor agonist. If CKD predominates, use metformin with dose adjustment and add a GLP-1 receptor agonist, but with caution in end-stage renal disease patients. Thiazolidines should be avoided in CHF. If necessary in CHF, add a DPP-4 inhibitor (gliptin), but not saxaglipitin, which has been shown to increase CHF.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Diet, Exercise, Hypertension, Smoking

Keywords: Atherosclerosis, Coronary Artery Disease, Diabetes Mellitus, Type 2, Diet, Dipeptidyl Peptidase 4, Dyslipidemias, Exercise, Frail Elderly, Glomerular Filtration Rate, Glucose, Hemoglobin A, Glycosylated, Heart Failure, Hyperglycemia, Hypertension, Hypoglycemia, Kidney Failure, Chronic, Life Style, Metformin, Metabolic Syndrome X, Mutation, Nutrition Therapy, Obesity, Primary Prevention, Quality of Life, Renal Insufficiency, Chronic, Risk Factors, Smoking, Smoking Cessation, Stroke, Thiazolidines, Weight Gain, Weight Loss

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