Alogliptin for type 2 diabetes

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Approved indication: type 2 diabetes
Nesina (Takeda)
6.25 mg, 12.5 mg and 25 mg tablets
Australian Medicines Handbook section 10.1.3

Alogliptin is the fifth dipeptidyl peptidase 4 (DPP4) inhibitor to be approved for diabetes in Australia, along with linagliptin (Aust Prescr 2012;35:70-1), saxagliptin (Aust Prescr 2011;34:89-91), vildagliptin (Aust Prescr 2010;33:89-95) and sitagliptin (Aust Prescr 2008;31:49-55).

DPP4 enzymes inactivate incretin hormones which are produced after a meal. These hormones promote insulin release and lower glucagon production which leads to lower serum glucose concentrations. By inhibiting DPP4 enzymes, the 'gliptins' prolong the effects of incretins and improve glycaemic control (Aust Prescr 2008;31:102-4 and 104-8).

Alogliptin's bioavailability is 100%. Following oral administration, peak plasma concentrations are reached after 1–2 hours. The drug is not extensively metabolised and clinically relevant pharmacokinetic drug interactions are not expected. Alogliptin has a terminal half-life of 21 hours and the majority of the dose (60–71%) is eliminated unchanged in the urine.

Alogliptin has been investigated in numerous randomised controlled trials in patients whose type 2 diabetes is not adequately managed with diet and exercise or other antidiabetic drugs. Some of these trials are listed in the Table.

Once-daily alogliptin was found to significantly reduce glycated haemoglobin (HbA1c) – a surrogate marker for glycaemic control – when added to stable doses of metformin,¹ glibenclamide,² pioglitazone³ or insulin (with or without metformin).⁴ HbA1c reductions were also seen when it was added to dual therapy with metformin and pioglitazone⁵ (see Table).

As initial therapy, alogliptin was significantly better than placebo at lowering HbA1c.⁶ It also showed benefit as initial therapy in combination with pioglitazone⁷ (see Table).

During trials, the most common adverse event with alogliptin was pruritus. Headache, diarrhoea, myalgia, rash, musculoskeletal pain, abdominal pain, nausea and infections (influenza, nasopharyngitis, upper respiratory tract infection) were also common (1–10% of patients).

Severe hypersensitivity reactions (e.g. angioedema, Stevens-Johnson syndrome), hepatic failure and pancreatitis have been reported in postmarketing surveillance. Alogliptin is not recommended in patients with severe hepatic impairment.

Hypoglycaemia can occur when alogliptin is added to insulin or a sulfonylurea so these drugs may need to be given at lower doses during combination therapy.

Alogliptin is a category B3 pregnancy drug. There are no data in humans so it is best avoided during pregnancy. Alogliptin was excreted in breast milk in animal studies so there is a risk of exposure to a breastfeeding infant.

Renal function should be assessed before patients start alogliptin. Dose reduction is recommended in patients with moderate (creatinine clearance 30 to 50 mL/min) or severe renal impairment (creatinine clearance <30 mL/min) and those with end-stage renal disease requiring dialysis. Experience in patients with severe renal disease is limited and caution is urged.

As with other DPP4 inhibitors, alogliptin is modestly effective at lowering HbA1c. It provides another option for monotherapy or as an add-on therapy when a patient's diabetes is not controlled by metformin, a sulfonylurea, a thiazolidinedione or insulin. It can also be added as a third option in patients already taking metformin and pioglitazone. Despite showing benefit in trials, alogliptin is currently not indicated for initial combination therapy in Australia.⁷

manufacturer provided additional useful information

The Transparency Score (

) is explained in New drugs: transparency, Vol 37 No 1, Aust Prescr 2014;37:27.

Notes on references