Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomised, double-blind, placebo-controlled study

• Published in: International journal of clinical practice (Esher) Vol. 63; no. 1; pp. 46 - 55
• Main Authors: Nauck, M. A., Ellis, G. C., Fleck, P. R., Wilson, C. A., Mekki, Q.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2009; Wiley-Blackwell; John Wiley & Sons, Inc
• Subjects: Aged; Biological and medical sciences; Blood Glucose - drug effects; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Double-Blind Method; Drug therapy; Drug Therapy, Combination; Effectiveness; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; General aspects; Glycated Hemoglobin A - metabolism; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Male; Medical sciences; Metformin - administration & dosage; Metformin - adverse effects; Middle Aged; Patient safety; Piperidines - administration & dosage; Piperidines - adverse effects; Side effects; Treatment Outcome; Uracil - administration & dosage; Uracil - adverse effects; Uracil - analogs & derivatives; Endocrinopathy; Type 2 diabetes; Human; Enzyme; Toxicity; Treatment efficiency; Multicenter study; Metabolic diseases; Patient; Medicine; Peptidases; Hypoglycemic agent; Randomization; Biguanides; Treatment; Placebo; Double blind study; Hydrolases; Dipeptidyl-peptidase IV inhibitor; Alogliptin; Metformin; Safety; Monotherapy
• ISSN: 1368-5031; 1742-1241; 1742-1241
• DOI: 10.1111/j.1742-1241.2008.01933.x

Summary Aims:  To evaluate the efficacy and safety of alogliptin, a new dipeptidyl peptidase‐4 inhibitor, for 26 weeks at once‐daily doses of 12.5 and 25 mg in combination with metformin in patients whose HbA1c levels were inadequately controlled on metformin alone. Methods and patients:  Patients with type 2 diabetes and inadequate glycaemic control (HbA1c 7.0‐10.0%) were randomised to continue a stable daily metformin dose regimen (≥ 1500 mg) plus the addition of placebo (n = 104) or alogliptin at once‐daily doses of 12.5 (n = 213) or 25 mg (n = 210). HbA1c, insulin, proinsulin, C‐peptide and fasting plasma glucose (FPG) concentrations were determined over a period of 26 weeks. Results:  Alogliptin at either dose produced least squares mean (SE) decreases from baseline in HbA1c of −0.6 (0.1)% and in FPG of −17.0 (2.5) mg/dl [−1.0 (0.1) mmol/l], decreases that were significantly (p < 0.001) greater than those observed with placebo. The between treatment differences (alogliptin – placebo) in FPG reached statistical significance (p < 0.001) as early as week 1 and persisted for the duration of the study. Overall, adverse events (AEs) observed with alogliptin were not substantially different from those observed with placebo. This includes low event rates for gastrointestinal side effects and hypoglycaemic episodes. There was no dose‐related pattern of AE reporting between alogliptin groups and few serious AEs were reported. Conclusion:  Alogliptin is an effective and safe treatment for type 2 diabetes when added to metformin for patients not sufficiently controlled on metformin monotherapy.