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.

Most patients with type 2 diabetes are managed in the primary care setting with specialist involvement where necessary. The first step in management should be establishing the goals of therapy. An individualised glycaemic target should be identified based on patient age, comorbidities and life expectancy.19 This target should be regularly reviewed and adjusted, as necessary, to match the patient’s specific characteristics and their current health status.

Lifestyle modification with dietary advice and an exercise plan should be the first prescription, with particular attention to weight management. An ideal body weight should be recommended, with a plan to achieve this. Although weight loss to target is recognised as challenging, and is not often achieved in practice, any improvement in body weight should be encouraged. Initial goals may focus on small improvements in weight, with both short- and long-term goals set and reviewed at each appointment. Beyond these recommendations, depending on initial glycaemic control at diagnosis or where glycaemic targets are not met, a proactive approach should be exercised with escalation of combination therapy as needed.

The case studies in Boxes 4 to 6 illustrate the tailoring of treatment to individuals.20-23

Choice of therapy and specific considerations

With an increasing array of treatment options, decisions in therapy may not be simple. Overall the fundamental principle of management is a patient-centred individualised approach. In recognition of the complexity of such decision-making, the Australian Diabetes Society has published a treatment algorithm to assist medical practitioners in both medicine selection and recommendations for glycaemic targets (Figure; algorithm available online at http://t2d.diabetessociety.com.au).10,11,19

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Specific drug classes currently available include biguanides (metformin), sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, thiazolidinediones, alpha-glucosidase inhibitors (acarbose) and sodium–glucose cotransporter-2 (SGLT2) inhibitors, as well as different insulins with various lengths of action. A summary of available treatment options is presented in the Table.24-39

First-line therapies

Metformin remains the first-line treatment, unless contraindicated. Its suitability as primary therapy is supported by the UKPDS data showing an association with reduced all-cause mortality.5 This finding has been repeated in a recent large meta-analysis.40

Second- and third-line therapies

Although the choice of second- and third-line agents is less prescriptive than that of a first-line agent, it should be guided by patient comorbidities, adverse effect profile and acceptability of the method of administration. Government subsidy (PBS) is also an important consideration, as cost plays a significant role, particularly where multiple agents are necessary.

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Common choices for second-line therapies include sulfonylureas, DPP-4 inhibitors and SGLT2 inhibitors. GLP-1 receptor agonists can also be used second line, although they may be less favoured by patients because they are administered by injection. Specific comorbidities may influence the choice of agent. For example, where weight is a concern, GLP-1 receptor agonists and SGLT2 inhibitors may have a favourable role. If patients have established CVD, sitagliptin will be safe, although the SGLT2 inhibitor empagliflozin may provide benefit. If the risk of hypoglycaemia is of particular concern, sulfonylureas should be dose-reduced, particularly in combination therapy, or avoided. Unless contraindicated or poorly tolerated, metformin should be continued; it should be noted that many agents are available in combination form with metformin. PBS restrictions may stipulate certain combinations must be trialled before other agents can be introduced.

There are now many approved combinations, containing triple oral or combined oral and injectable agents, for use as third-line therapies. Again, metformin should be continued wherever possible.

Insulin may be considered at any stage in therapy, particularly where glycaemic control is significantly poor (HbA1c > 75 mmol/mol [9%]). Insulin has often been used in combination therapy with metformin, although more recently has been approved for use in combination with DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors. Weight gain is a recognised side effect of insulin, although this should not necessarily deter its prescription. In combination with other agents, insulin can be used at lower doses, thus minimising weight gain. Additionally it can be withdrawn at any point depending on the individual patient, and thus does not need to be used in an ongoing sense if effects are unfavourable.

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Treatment of specific patient groups

Renal failure

The choice of treatment for patients with type 2 diabetes and renal failure is limited because of altered drug metabolism and associated risks of adverse effects, including hypoglycaemia. Such considerations become more important with advancing chronic kidney disease (CKD), particularly when estimated glomerular filtration rate (eGFR) is below 30 mL/min (stages 4 and 5 CKD), and medications may require dose reduction or cessation if contraindicated.