Alogliptin (Nesina) — an option for add-on therapy in type 2 diabetes mellitus

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.

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

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.

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