Pharmacological therapies in Australia for type 2 diabetes

There is consensus among guidelines that metformin is standard first-line pharmacotherapy for patients with type 2 diabetes.^1-4 If metformin is contraindicated or not tolerated, a sulfonylurea is a suitable option.^{1, 2 , 4}

There is limited comparative evidence for various combinations of medicines to inform prescribing of a second or third glucose-lowering medicine.²

Subsequent add-on therapies should be individualised, taking into consideration patient characteristics and preferences, synergistic effects of differing medicine combinations and licensed combinations.^1-3

Long-term clinical experience and data for sulfonylureas, as well as cost-effectiveness, makes them the usual second-line add-on agent to metformin.^{2, 3}

Consider an alternative agent for patients in whom sulfonylureas are contraindicated or not tolerated and for those who experience problematic hypoglycaemia or weight gain.²

Dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium–glucose co-transporter-2 (SGLT2) inhibitors are alternative second-line add-on medicines and are PBS subsidised for use with either metformin or a sulfonylurea.^{1, 2, 5}

Glucagon-like peptide-1 (GLP-1) analogues and thiazolidinediones are also PBS subsidised as dual therapy with metformin or a sulfonylurea but only when a metformin/sulfonylurea combination is contraindicated or not tolerated.⁵

Due to safety concerns, use of thiazolidinediones is generally limited to patients with severe insulin resistance or patients unable to tolerate other glucose-lowering medicines.^3-5

Acarbose has an unrestricted PBS listing; however, high rates of GI adverse effects result in limited use.^{2, 4, 5} Acarbose is an option for patients who cannot achieve glycaemic control with other non-insulin medicines.³ Due to its mechanism of action it may also be useful for patients with postprandial hyperglycaemia.^{1, 4}

Third-line treatment of type 2 diabetes involves adding a third medicine to existing dual therapy.^{3, 5} Clearly ineffective therapies should be discontinued and substituted with another medicine.² Metformin should generally be continued unless contraindications develop.²

Glucose-lowering medicines currently PBS subsidised for triple therapy with metformin and a sulfonylurea are:⁵

• DPP-4 inhibitors: saxagliptin^a and sitagliptin^a
• SGLT2 inhibitor: dapagliflozin^a
• GLP-1 analogue: exenatide
• thiazolidinedione: pioglitazone
• acarbose.

A 2014 position statement of the Australian Diabetes Society (ADS) outlines efficacy and safety data for these triple therapy combinations.²

1. Fixed-dose combination(s) of these medicines with metformin are also PBS subsidised for triple oral therapy with metformin and a sulfonylurea.^5-8

Insulin can be started at any stage in the treatment of type 2 diabetes.² Although it is often reserved until treatment targets cannot be met with other non-insulin medicines,³ the ADS recommends it be considered early if blood glucose levels are very high.²

Insulin is commonly started as an add-on to oral glucose-lowering medicines, usually metformin.^{2, 3, 5} Combinations with newer agents including DPP-4 inhibitors, SGLT2 inhibitors and GLP-1 analogues are effective but not all PBS subsidised.⁵

Currently, in addition to glucose-lowering medicines with Unrestricted Benefits listings, the following medicines are PBS subsidised for use in combination with insulin:⁵

• dapagliflozin
• dapagliflozin and metformin XR⁸
• pioglitazone
• exenatide.

Several metformin fixed-dose combinations (FDCs) are PBS listed for the treatment of type 2 diabetes (see Table 1).⁵ These FDC products are PBS subsidised for the same combinations as the individual non-metformin medicine component.^5-8

FDC products may improve adherence by simplifying the treatment regimen but they are not suitable for all patients because of limited combination and dosing options.

As with all FDC products, stabilise patients on the individual components taken separately before switching to the combination product.

The ADS and RACGP offer treatment algorithms for type 2 diabetes that include the newer glucose-lowering medicines.^{1, 2} PBS subsidy for medicine combinations may change – refer to the PBS for full restriction criteria.