From 1 December 2013 the dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin will join the other gliptins already listed on the PBS — sitagliptin (Januvia), vildagliptin (Galvus), saxagliptin (Onglyza) and linagliptin (Trajenta).
Alogliptin (25 mg, 12.5 mg and 6.25 mg) is a treatment option for dual oral therapy in combination with either metformin or a sulfonylurea for people with type 2 diabetes who are not adequately controlled with either drug alone.1PBS listing restrictions
The Authority required (Streamlined) listing of alogliptin permits use in dual oral combination therapy with metformin or a sulfonylurea in people with type 2 diabetes whose HbA1c is > 7% (53 mmol/mol) despite treatment with either metformin or a sulfonylurea. Alogliptin may be prescribed by nurse practitioners.1
The subsidised use of alogliptin is similar to that for the other DPP-4 inhibitors. However, the PBS listing of alogliptin permits its use as an add-on to metformin without using a sulfonylurea first. It is the first DPP-4 inhibitor to receive this PBS listing for use in patients without contraindication or intolerance to a combination of metformin and a sulfonylurea.
Efficacy is similar across the class of gliptins
Alogliptin, sitagliptin, vildagliptin, saxagliptin and linagliptin all improve glycaemic control in diabetes not adequately controlled with metformin or a sulfonylurea.
When combined with metformin, alogliptin appears to provide improvements in HbA1c similar to those with the other gliptins. However, no head-to-head trials have compared the efficacy of alogliptin with other gliptins or any of the other available anti-diabetic drugs.
In several large trials of up to 26 weeks' duration, oral alogliptin in combination with other oral glucose-lowering agents (metformin, glyburide or pioglitazone)2-4 improved glycaemic control and was generally well tolerated in people with inadequately controlled type 2 diabetes.
For people on oral antihyperglycaemic agents (metformin, glyburide or pioglitazone), the mean least squares (LS) changes in HbA1c from baseline to week 26 were significantly reduced (p < 0.001) with addition of alogliptin compared with placebo (Table 1).2-4
Table 1 Mean LS change in HbA1c from baseline to week 262-4
Antihyperglycaemic agent |
Alogliptin |
Placebo |
---|---|---|
Metformin |
–0.6% |
–0.1% |
Glyburide |
–0.52% |
+0.01% |
Pioglitazone |
–0.80% |
–0.19% |
Alogliptin has similar advantages to those of the other DPP-4 inhibitors for some people with type 2 diabetes. As add-on therapy it may be a useful alternative to a sulfonylurea, a glitazone, a glitinide* or insulin for people who are overweight or at high risk of hypoglycaemia. Alogliptin is associated with a similar incidence of hypoglycaemia to that of placebo and has a weight-neutral effect.5
*Please note that there are currently no glitinides available in Australia; for further information refer to our Medicines and treatments pages about Repaglinide.
What to consider before prescribing
Alogliptin is well tolerated and has a good safety profile.2-4 However, the long-term safety profile of the gliptins is yet to be established. A long-term, open-label extension study that investigated the safety of alogliptin in people with type 2 diabetes has been completed, but the results have not been published as yet.6
A recent clinical trial investigated the CV safety of alogliptin (n = 2701) versus placebo (n = 2679) in addition to standard care. In people with type 2 diabetes who had a recent acute coronary syndrome, no increase in rates of adverse CV outcomes (including CV death, and non-fatal MI or stroke) were seen for alogliptin compared with placebo.7 But the long-term CV impact of alogliptin is yet to be determined.
The recommended dose of alogliptin is 25 mg once daily as add-on therapy to metformin or a sulfonylurea. No dose reduction is recommended when alogliptin is used in combination with metformin and/or a thiazolidinedione. When alogliptin is used in combination with a sulfonylurea or insulin, a lower dose of the sulfonylurea or insulin may be considered to reduce the risk of hypoglycaemia.8
Reduce alogliptin dose in patients with eGFR 30–50 mL/min to 12.5 mg and in patients with eGFR < 30 mL/min to 6.25 mg. Alogliptin is not recommended for use in patients with severe hepatic impairment.8
For further information
References
- Australian Government Department of Health and Ageing. July 2013 PBAC Outcomes \u2013 Positive Recommendations. 2013. http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/pbac-outcomes (accessed 30 August 2013).
- Nauck MA, Ellis GC, Fleck PR, et al. Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomised, double-blind, placebo-controlled study. Int J Clin Pract 2009;63:46\u201355. [PubMed]
- Pratley RE, Kipnes MS, Fleck PR, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy. Diabetes Obes Metab 2009;11:167\u201376. [PubMed]
- Pratley RE, Reusch JE, Fleck PR, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Curr Med Res Opin 2009;25:2361\u201371. [PubMed]
- Scott LJ. Alogliptin: a review of its use in the management of type 2 diabetes mellitus. Drugs 2010;70:2051\u201372. [PubMed]
- Takeda Global Research and Development Center Inc. A long-term, open-label extension study to investigate the long-term safety of SYR110322 (SYR-322) in subjects with type 2 diabetes. ClinicalTrials.gov identifier NCT00306384: US National Institutes of Health, 2013. http://clinicaltrials.gov (accessed 24 September 2013).
- White WB, Cannon CP, Heller SR, et al. Alogliptin after Acute Coronary Syndrome in Patients with Type 2 Diabetes. N Engl J Med 2013; 369:1327\u201335. [PubMed]
- Takeda Pharmaceuticals Australia Pty Ltd. Nesina Product Information. 2013; 8 October 2013).
- National Prescribing Service Limited. Sitagliptin, vildagliptin and saxagliptin \u2014 dipeptidyl peptidase-4 inhibitors ('gliptins') add-on therapy in type 2 diabetes mellitus. NPS RADAR, July 2011. http://www.nps.org.au/publications/health-professional/nps-radar/2011/july-2011/gliptins (accessed 2 August 2013).
- National Prescribing Service Limited. Another dipeptidyl peptidase-4 inhibitor ('gliptin') for add-on therapy in type 2 diabetes mellitus. NPS RADAR 2012. http://www.nps.org.au/publications/health-professional/nps-radar/2012/march-2012/brief-item-linagliptin (accessed 5 August 2013).