Linagliptin (Trajenta) 5 mg tablets were listed on the Pharmaceutical Benefits Scheme (PBS) on 1 March 2012. The Pharmaceutical Benefits Advisory Committee recommended listing linagliptin on a cost-minimisation basis compared with sitagliptin.1 Like the other gliptins, the PBS listing allows the use of linagliptin when people with type 2 diabetes have an HbA1c > 53 mmol/mol (> 7%) despite use of metformin or a sulfonylurea, and when the combination of metformin and a sulfonylurea is contraindicated or not tolerated. Linagliptin is not PBS subsidised for use in triple therapy (in combination with metformin and a sulfonylurea), as monotherapy or in combination with a thiazolidinedione or exenatide.
Linagliptin 5 mg reduces HbA1c by 0.64% compared with placebo when added to metformin.2 No head-to-head trials of linagliptin and any of the other available antidiabetic drugs have been published.* Interim results from an ongoing trial (n = 1560) comparing linagliptin and glimepiride in people already taking metformin are reported in US and Australian regulatory documents. After 52 weeks, glimepiride was superior to linagliptin in lowering HbA1c and fasting plasma glucose. Significantly more patients required a third antidiabetic drug (pioglitazone) to control blood glucose than in the glimepiride group (16.3% vs 12.1%) but significantly fewer discontinued therapy due to adverse events (5.8% vs 9.9%). More people in the glimepiride group were reported to have experienced hypoglycaemia than in the linagliptin group (30.5% versus 5.3%). The group taking linagliptin lost weight while those taking glimepiride gained weight.3,4
The recommended dose is 5 mg once daily.5 Unlike the other gliptins (sitagliptin, vildagliptin and saxagliptin) which are cleared by the kidney, linagliptin is mainly excreted unchanged in faeces. No dose reduction in renal or hepatic impairment is required.4–6
*One trial compared linagliptin with voglibose, an alpha-glucosidase inhibitor that is not available in Australia.7 An open-label glimepiride arm (n = 65) was included in a 12-week dose-ranging study.8
- Pharmaceutical Benefits Advisory Committee. Positive recommendations made by the PBAC \u2014 November 2011. Canberra: Australian Government Department of Health and Ageing, 2011. http://www.health.gov.au/internet/main/publishing.nsf/Content/pbacrec-nov11-positive (accessed 1 February 2012).
- Taskinen MR, Rosenstock J, Tamminen I, et al. Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab 2011;13:65\u201374. [PubMed]
- Center for Drug Evaluation and Research. Tradjenta \u2014 Application Number 201280Orig1s000 Medical Reviews. Rockville, Maryland: Food and Drug Administration, 2011. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201280Orig1s000MedR.pdf (accessed 1 February 2012).
- Therapeutic Goods Administration. Australian public assessment report for linagliptin. Canberra: TGA, 2011. http://www.tga.gov.au/pdf/auspar/auspar-trajenta.pdf (accessed 1 February 2012).
- Boehringer Ingelheim Pty Limited. Trajenta product information 1 November 2011. Australia: 2011.
- Center for Drug Evaluation and Research. Tradjenta \u2014 Application Number 201280Orig1s000 Clinical pharmacology and biopharmaceutics reviews. Rockville, Maryland: Food and Drug Administration, 2011. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201280Orig1s000ClinPharmR.pdf (accessed 1 February 2012).
- Kawamori R, Inagaki N, Araki E, et al. Linagliptin monotherapy provides superior glycaemic control versus placebo or voglibose with comparable safety in Japanese patients with type 2 diabetes: a randomized, placebo and active comparator-controlled, double-blind study. Diabetes Obes Metab 2011; doi: 10.1111/j.1463-1326.2011.01545.x. [PubMed]
- Forst T, Uhlig-Laske B, Ring A, et al. Linagliptin (BI 1356), a potent and selective DPP-4 inhibitor, is safe and efficacious in combination with metformin in patients with inadequately controlled Type 2 diabetes. Diabet Med 2010;27:1409\u201319. [PubMed]