ADA/EASD
CONSENSUS
REPORT

The latest consensus statement from the American Diabetes Association and European Association for the Study of Diabetes (ADA/EASD) on the management of hyperglycaemia in type 2 diabetes (T2D) puts new emphasis on drugs that have benefits beyond their ability to lower blood glucose.

1. GOALS OF TREATMENT


Maintain quality of life

The goals of treatment for T2D are to prevent or delay complications and to maintain quality of life.


Glycaemic control and
CV management

This requires control of glycaemia and comprehensive cardiovascular risk factor management.


Reductions in
complications

Good glycaemic control produces substantial and lasting reductions in both the onset and the progression of complications.


Individualised treatment targets

Treatment targets should be individualised, taking into account patient preferences and goals, risk of adverse effects of therapy such as hypoglycaemia and weight gain, and patient characteristics including frailty and comorbidities such as CVD, HF and CKD.

2. PRINCIPLES OF CARE

RECOMMENDATIONS

Providing patient care that acknowledges multimorbidity and is responsive to patient preferences is essential to effective diabetes management.

Shared decision making, with decision aids that show the absolute benefit and risk of alternative treatment options, is a useful strategy.

Diabetes Self-Management Education and Support (DSMES) is a key intervention to enable people with diabetes to make informed decisions and to take responsibility for their own day-to-day management. DSMES programmes usually involve face-to-face contact in group or individual sessions with trained educators. DSMES programmes delivered from diagnosis can promote medication adherence, healthy eating, and physical activity, and increase self-efficacy.

Suboptimal adherence, including poor persistence, to therapy affects almost half of people with diabetes, leading to suboptimal glycaemic and cardiovascular disease CVD risk factor control, as well as increased risk of diabetes complications, mortality, hospital admissions, and health care costs.

Factors contributing to inconsistent medication use include:

  • Patient-perceived lack of medication efficacy
  • Fear of hypoglycaemia
  • Adverse effects of medication

Therapeutic or clinical inertia refers to failure to intensify therapy when treatment targets are not met. Avoiding inertia helps to improve glycaemic control. Having a multidisciplinary team that includes nurse practitioners or pharmacists may help to reduce inertia, as does a coordinated chronic care model, while a fragmented healthcare system may contribute to inertia.

The expanding number of glucose-lowering treatments and increasing information about their benefits and risks provides more options – but can complicate decision-making. When selecting the most appropriate medication, consider the presence of atherosclerotic CVD (ASCVD), presence or risk of heart failure (HF), and renal disease. Also consider weight and hypoglycaemic risk.

3. CHOOSING GLUCOSE LOWERING MEDICATION

RECOMMENDATIONS

ADA/EASDʼs new approach takes into account recent evidence for the benefit of specific SGLT2i's and GLP-1 RAs to reduce the risk of cardiovascular events: cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, hospitalisation for heart failure, and also renal disease in the setting of established CVD, and their use is considered compelling in this patient group.

For patients with clinical CVD not meeting individualised glycaemic targets with metformin (or in whom metformin is not tolerated or contraindicated) add an SGLT2i or GLP-1 RA with proven CV benefit to their treatment programme. In patients where HF is a concern, an SGLT2i is recommended, if eGFR is adequate.

Among the GLP-1 RAs, the strongest evidence for cardiovascular benefit was for liraglutide, but the CVOTs showed no significant effect on hospitalisation for HF.

The cardiovascular outcome trials (CVOTs) for canagliflozin and empagliflozin included in the consensus report have shown cardiovascular benefits*

*The DECLARE-TIMI-58 trial had not been published at the time the consensus report was developed, and is therefore not included

Patients with T2D and kidney disease are at an increased risk of CV events.

Consistent benefits in renal outcomes (reduction in albuminuria, renal composite: 40% reduction in eGFR/doubling of serum creatinine, ESKD, renal or CV death) were reported with SGLT2is, whereas results were mixed with GLP1-RAs.

CVOTs with DPP-4is showed modest reductions in albuminuria only.

4. PUTTING IT ALL TOGETHER: STRATEGIES FOR IMPLEMENTATION

For increasing numbers of patients, presence of specific co-morbidities (ASCVD, HF, CKD, obesity), safety concerns (e.g. hypoglycaemia) cost of medication dictate the specific approach to the choice of medication.

RECOMMENDATIONS

Metformin is the preferred initial therapy and should be added to lifestyle measures in patients newly diagnosed with type 2 diabetes. This recommendation is based on the efficacy, safety, tolerability, low cost, and extensive clinical experience with this medication. Metformin is associated with less hypoglycaemia and weight gain than insulin or sulphonylureas but should not be in patients with an eGFR <30 ml/min/1.73m2 and the dose reduced if eGFR falls below <45 ml/min/1.73m2.

While there is some support for initial combination therapy due to greater initial reduction of HbA1c than can be provided by metformin alone, there is little evidence that this approach is superior to sequential addition of medications for maintaining glycaemic control.

Choice of medication after metformin

Sulfonylureas and insulin are associated with an increased risk for causing hypoglycaemia and are not preferred for patients in whom this is a concern.

For patients prioritising weight loss or weight maintenance, important considerations include the weight reduction associated with SGLT2i's and GLP-1 RAs, the weight neutrality of DPP-4 inhibitors, and the weight gain associated with sulfonylureas, basal insulin and thiazolidinediones (TZDs).

An important consideration is the cost of medications; sulfonylureas, pioglitazone and recombinant human insulins are relatively inexpensive. Short-term acquisition costs, longer-term treatment cost and cost-effectiveness should be considered in clinical decision-making.

Second intensification

It is common in people with long-standing diabetes to require more than two glucose-lowering agents, often including insulin.

Intensification of treatment beyond two medications follows the same general principles as the addition of a second medication.

The efficacy of third and fourth medications will be generally less than expected if used in mono- or dual therapy. As more medications are added, there is an increased risk of adverse effects. It is important to consider medication interactions and whether regimen complexity may become an obstacle to adherence.

The dose of background medication may need to be adjusted to avoid hypoglycaemia when adding a new agent to a regimen containing insulin or a sulfonylurea.

5. CONCLUSION


LIFESTYLE &
EDUCATION

New ADA/EASD recommendations include additional focus on lifestyle management and diabetes self-management education and support.


CHOICE OF
TREATMENT

Consider patient comorbities (ASCVD, CKD, HF), clinical characteristics (HbA1c, age, weight), adverse effects (hypoglycaemia) and cost.


ASCVD

After metformin, for patients with clinical cardiovascular disease, a GLP-1 RA or SGLT2i, if eGFR is adequate, with proven cardiovascular benefit is recommended.


CKD/HF

For patients with ASCVD, where chronic kidney disease or heart failure predominate, if eGFR is adequate, an SGLT2i with proven benefit is recommended.

Abbreviations

ASCVD, atherosclerotic cardiovascular disease
CKD, chronic kidney disease
CV, cardiovascular
CVD, cardiovascular disease
CVOT, cardiovascular outcomes trial
DSMES, Diabetes Self-Management Education and Support
eGFR, estimated glomerular filtration rate
ESRD, end stage renal disease
GLP-1 RA, glucagon-like peptide receptor agonist
HbA1c, glycated haemoglobin
HF, heart failure
SGLT2i, sodium glucose co-transporter 2 inhibitor
SU, sulfonylurea
T2D, type 2 diabetes
TZD, thiazolidinediones

Reference

Davies MJ, DʼAlessio DA, Fradkin J, et al. 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). Diabetes Care 2018;41:2669-2701 https://doi.org/10.2337/dci18-0033

Job Code: UK/DIA-19071 Date of preparation: August 2019