Open Access
Feature Article

Type 2 diabetes: tailoring a treatment approach

Open Access
Feature Article

Type 2 diabetes: tailoring a treatment approach

Kharis Burns, N. Wah Cheung

Figures

Dr Burns is a Consultant Endocrinologist in the Department of Diabetes and Endocrinology at Westmead Hospital, Sydney; and Clinical Associate Lecturer at Sydney Medical School, The University of Sydney. Professor Cheung is an Endocrinologist and Director of the Department of Diabetes and Endocrinology at Westmead Hospital, Sydney; and Clinical Professor at Sydney Medical School, The University of Sydney, Sydney, NSW.

Key trials on glycaemic targets

Among the wealth of research in the area of reducing diabetes-related end points through achieving HbA1c targets, four key randomised controlled trials have contributed significantly to the current diabetes management principles. These trials are discussed in Box 1.3-8

The legacy effect of the glycaemic target trials

Long-term follow up of the four key large clinical trials has shown that tight control in the period following diabetes diagnosis can have a sustained effect for years to come, even if glycaemic control is later relaxed. Results from the UKPDS 10-year follow up found early glycaemic control (HbA1c below 53 mmol/mol [7%]) mitigated long-term risk of any diabetes-related end point and microvascular disease.9 The risk of diabetes-related death, MI and death from any cause was also lower in those who received intensive therapy early despite later merging of HbA1c from the two arms (sulfonylurea–insulin group and metformin group).9 This concept was termed the ‘legacy effect’, and supports optimal glycaemic control in the early stages of disease.8 It emphasises the importance of considering duration of type 2 diabetes when tailoring treatment.

Recommended glycaemic targets

Based on the body of evidence, the Australian Diabetes Society has developed guidelines to assist clinicians in decision-making in this area, the position statement Individualisation of Glycated Haemoglobin Targets for Adults with Diabetes Mellitus.10These recommendations are endorsed by the Royal Australian College of General Practitioners (RACGP) and are available in their and Diabetes Australia’s current guidelines, General Practice Management of Type 2 Diabetes: 2016–18.11

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It is generally accepted that an HbA1c target of 53 mmol/mol (7%) should be aimed for in most cases, with recommended targets tightened (≤ 48 mmol/mol, or 6.5%) or relaxed (≤ 64 mmol/mol, or 8%) in some individuals (Box 2).10,11

Cardiovascular risk of glucose-lowering agents

The link between type 2 diabetes, cardiovascular disease (CVD) and related mortality is well established. Recently a few major trials have investigated the cardiovascular risk of glucose-lowering agents, because of concerns about a lack of long-term safety data in this area. The results of these trials may assist clinicians in choosing agents for patients with both of these issues. The trials are discussed in Box 3.12-17

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Interpreting the key cardiovascular risk trials

To date the evidence from these major cardiovascular risk trials of various glucose- lowering agents suggests the relative safety of DPP-4 inhibitors in type 2 diabetes and CVD, albeit a higher risk of heart failure with saxagliptin and possibly alogliptin. SGLT2 inhibitors, specifically empagliflozin, and GLP-1 receptor agonists, specifically liraglutide, appear to confer a CV benefit patients with established CVD. Several key trials investigating other agents within these classes are currently under way.

The findings from these trials, however, need to be interpreted in the context of the populations in which they were conducted. Important points to consider include the age and sex of the patients, the duration of pre-existing diabetes, the presence of comorbidities including microvascular and cardiovascular disease, the initial HbA1c and the use of concomitant therapies. The risk of hypoglycaemia also needs consideration. Furthermore, the results could possibly apply only to the agent trialled, and not necessarily be a class effect.

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Treatment options

The past decade has witnessed major advances in treatment options for type 2 diabetes, leading to a shift in the management paradigm. With the rise in prevalence of this condition, there are still a significant number of patients who do not meet current recommendations for glycaemic targets. Analysis of medical records in primary care in Australia from 2005 to 2013 found that 40% of patients had elevated HbA1c.18 This is in part due to treatment inertia. Health practitioners now have a range of choices in therapy aimed at regulating blood glucose control with concomitant focus on reducing the incidence of specific comorbidities such as obesity and limiting adverse effects. Inevitably, with disease progression, many patients will require insulin therapy, although in the interim there are many available options for glycaemic control.