Saxagliptin (Onglyza™) is a dipeptidyl peptidase 4 inhibitor widely approved for the treatment of type 2 diabetes mellitus. In the EU, saxagliptin is indicated as combination therapy with metformin, a sulfonylurea, a thiazolidinedione, or insulin (with or without metformin) for the treatment of adult patients with type 2 diabetes, including those with mild to severe renal impairment. This article reviews the clinical efficacy and tolerability of add-on saxagliptin therapy in patients with type 2 diabetes, in line with its approved indications in the EU, and summarizes the drug’s pharmacological properties.
The clinical efficacy of saxagliptin 5 mg/day in combination with metformin, glibenclamide (glyburide), a thiazolidinedione, or insulin (with or without metformin) has been demonstrated in several randomized, double-blind, placebo-controlled, multicentre, phase III trials (18–104 weeks in duration) in patients with type 2 diabetes. In these trials, glycosylated haemoglobin (HbA1c) was changed from baseline (primary endpoint) by a greater extent with add-on saxagliptin 5 mg/day (−1.09% to +0.03%) than with comparator regimens (−0.44% to +0.69%). Two other randomized, double-blind trials showed that saxagliptin 5 mg/day as add-on therapy to metformin was noninferior to uptitrated glipizide in terms of lowering HbA1c (−0.74% vs −0.80%) at 52 weeks, or sitagliptin (−0.52% vs −0.62%) at 18 weeks. Saxagliptin 2.5 mg/day as add-on to existing anti-diabetic therapy was also effective for up to 52 weeks in a randomized, double-blind, placebo-controlled, multicentre trial in patients with type 2 diabetes and renal impairment (HbA1c was reduced by 1.08% vs 0.36%; p ≤ 0.007).
Saxagliptin as add-on therapy for up to 4 years was generally well tolerated in clinical trials. Treatment with saxagliptin did not increase the risk of hypoglycaemia or cardiovascular outcomes relative to placebo or active comparators, and was generally weight neutral.
In conclusion, saxagliptin is a useful option as add-on therapy to metformin, a sulfonylurea, a thiazolidinedione, or insulin (with or without metformin) in patients with type 2 diabetes who require combination therapy.
Various sections of the manuscript reviewed by:
D.S.H. Bell, Division of Endocrinology, University of Alabama Medical School, Southside Endocrinology, Birmingham, AL, USA; D. Bhatnagar, The Royal Oldham Hospital and University of Manchester Cardiovascular Research Group, Oldham, UK; M. Christensen, Diabetes Research Division, Department of Internal Medicine F, Gentofte Hospital, Copenhagen, Denmark; G. Dimitriadis, 2nd Department of Internal Medicine, Research Institute and Diabetes Center, University of Athens Medical School, Attikon University Hospital, Athens, Greece; J.G. Eriksson, Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland; P. Holt, School of Healthcare, University of Leeds, Leeds, UK; J.R. Petrie, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK; A.J. Scheen, Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, University of Liège, Liège, Belgium.
Sources: Medical literature (including published and unpublished data) on ‘saxagliptin’ was identified by searching databases since 1996 (including MEDLINE, EMBASE and in-house AdisBase), bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.
Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘saxagliptin’ and ‘type 2 diabetes mellitus’ or ‘non insulin dependent diabetes mellitus’. Searches were last updated 19 December 2011.
Selection: Studies in patients with type 2 diabetes mellitus who received saxagliptin. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Saxagliptin, type 2 diabetes mellitus, pharmacodynamics, pharmacoeconomics, pharmacokinetics, therapeutic use, tolerability