Overview

The content of this evidence summary was up-to-date in May 2013. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Summary

When added to certain dual and triple therapy regimens, the dipeptidyl peptidase-4 (DPP-4) inhibitor, alogliptin, reduces glycated haemoglobin (HbA1c) levels by around 5.5 mmol/mol compared with placebo. However, there are no published RCTs of alogliptin added to metformin and a sulfonylurea, or alogliptin compared with other DPP-4 inhibitors or glucagon-like peptide-1 (GLP-1) mimetics. No serious safety concerns have emerged so far; however, there are no long-term safety data and no data on the effect of alogliptin on the long-term complications of type 2 diabetes.

Effectiveness

  • Alogliptin as add-on therapy reduces HbA1c by around 5.5 mmol/mol (0.5%) compared with placebo (4 RCTs of dual therapy lasting 26 weeks, 2 RCTs of triple therapy lasting 26 and 52 weeks).

Safety

  • No serious safety concerns have emerged so far.

  • Proportionally more hypoglycaemia and drug-related skin and subcutaneous disorders with alogliptin triple therapy compared with dual therapy, but statistical significance not reported (1 RCT of 52 weeks).

Patient factors

  • Once-daily oral dosage regimen.

  • Tolerability appears similar to other oral blood glucose-lowering drugs (around 2% to 4% reported adverse effects leading to discontinuation in 2 RCTs of 26 and 52 weeks).

Cost

  • The cost of alogliptin is not yet known.

  • The 28-day drug cost for the DPP-4 inhibitors currently available ranges from £31.60 to £33.26.

Key points from the evidence

Alogliptin is a DPP-4 inhibitor that aims to lower blood glucose levels.

A submission for a marketing authorisation for alogliptin benzoate (brand name Vipidia) was made to the European Medicines Agency in May 2012. It is anticipated that alogliptin will be launched in the UK in the fourth quarter of 2013. The proposed indication is to improve glycaemic control in adults with type 2 diabetes mellitus in combination with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, have not provided adequate glycaemic control.

This evidence summary is based on 2 randomised controlled trials (RCTs) that provide published evidence on the use of alogliptin to treat people with type 2 diabetes in line with current use of DPP-4 inhibitors in UK clinical practice. In these trials, alogliptin was added to existing metformin monotherapy for 26 weeks (dual therapy; Nauck et al. 2009) or used in combination with metformin and pioglitazone for 52 weeks (triple therapy; Bosi et al. 2011). Four other published placebo-controlled RCTs that investigated the efficacy of alogliptin added to other blood glucose-lowering drugs in dual or triple therapy for 26 weeks are discussed briefly in the Evidence review.

Across the 6 RCTs, using alogliptin 12.5 mg or 25 mg once daily as add-on therapy to a range of concurrent treatment options led to an additional reduction in HbA1c of about 5.5 mmol/mol (0.5 percentage points) compared with placebo.

Alogliptin appeared well tolerated in the 2 RCTs reviewed in this evidence summary, with most adverse events reported to be of mild or moderate intensity. The proportions of patients experiencing serious adverse events or adverse events leading to study drug discontinuation were low across all groups. In Bosi et al. (2011), hypoglycaemia was reported by proportionally more patients on alogliptin triple therapy (4.5% [18/404]) compared with dual therapy (1.5% [6/399]), as were drug-related skin and subcutaneous disorders (5.2% [21/404] with triple therapy compared with 2.3% [9/399] with dual therapy) but statistical significance was not reported.

The NICE clinical guideline on type 2 diabetes: the management of type 2 diabetes, published in 2009, included the only 2 DPP-4 inhibitors licensed at the time the guideline was developed: sitagliptin and vildagliptin. Since then, 2 further DPP-4 inhibitors have been licensed in the UK: saxagliptin and linagliptin. All 4 currently available DPP-4 inhibitors (but not alogliptin) will be included in an update of this guideline, the publication date of which is still to be confirmed.

Local decision makers will need to consider the available evidence on efficacy and safety, as well as cost and individual patient factors, when making decisions about using alogliptin.

Update

The following information has become available since this ESNM was produced.

January 2014: Availability of alogliptin

Alogliptin has been launched in the UK as Vipidia (alogliptin benzoate) and Vipdomet (metformin hydrochloride plus alogliptin benzoate). The cost of Vipidia (excluding VAT, all strengths) is £26.60 for 28 tablets. The cost of Vipdomet (excluding VAT) is £26.60 for 56 tablets. Costs taken from MIMS, September 2014.

October 2013: Study finds no benefit from alogliptin on cardiovascular outcomes in people with a recent acute coronary syndrome

A large randomised controlled trial (EXAMINE) has found that adding alogliptin to other blood-glucose-lowering medication did not reduce the risk of cardiovascular events in people with type 2 diabetes who had had a recent acute coronary syndrome, over a median of 18 months. This study was summarised in a medicines evidence commentary.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.