Efficacy and Safety of Saxagliptin When Added to Metformin Therapy in Patients With Inadequately Controlled Type 2 Diabetes With Metformin Alone

• Published in: Diabetes care Vol. 32; no. 9; pp. 1649 - 1655
• Main Authors: DeFronzo, Ralph A, Hissa, Miguel N, Garber, Alan J, Luiz Gross, Jorge, Yuyan Duan, Raina, Ravichandran, Shoba, Chen, Roland S
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-09-2009
• Subjects: Adamantane - administration & dosage; Adamantane - adverse effects; Adamantane - analogs & derivatives; Adamantane - pharmacology; Adamantane - therapeutic use; Adolescent; Adult; Aged; Apoptosis; Biological and medical sciences; Blood Glucose - drug effects; Care and treatment; Dextrose; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes therapy; Diabetes. Impaired glucose tolerance; Diabetics; Dipeptides - administration & dosage; Dipeptides - adverse effects; Dipeptides - pharmacology; Dipeptides - therapeutic use; Double-Blind Method; Drug abuse; Drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glucose; Heart failure; Humans; Hypoglycemia; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Male; Medical research; Medical sciences; Medicine, Experimental; Metabolic diseases; Metformin - administration & dosage; Metformin - adverse effects; Metformin - pharmacology; Metformin - therapeutic use; Middle Aged; Miscellaneous; Original Research; Patient care planning; Pharmaceutical industry; Physical examinations; Placebos; Public health. Hygiene; Public health. Hygiene-occupational medicine; Research methodology; Safety; Substance abuse treatment; Treatment Outcome; Type 2 diabetes; Young Adult; United States; Switzerland; Dipeptidyl-peptidase IV; Endocrinopathy; Type 2 diabetes; Human; Nutrition; Enzyme; Toxicity; Treatment efficiency; Enzyme inhibitor; Controlled diabetes; Patient; Metabolic diseases; Peptidases; Hypoglycemic agent; Biguanides; Treatment; Gliptine derivatives; Hydrolases; Dipeptidyl-peptidase IV inhibitor; Metformin; Safety; Endocrinology; Saxagliptin
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc08-1984

OBJECTIVE: This 24-week trial assessed the efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes with inadequate glycemic control with metformin alone. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, placebo-controlled study of saxagliptin (2.5, 5, or 10 mg once daily) or placebo plus a stable dose of metformin (1,500-2,500 mg) in 743 patients (A1C greater-than-or-equal7.0 and [less-than or equal to]10.0%). Efficacy analyses were performed using an ANCOVA model using last observation carried forward methodology on primary (A1C) and secondary (fasting plasma glucose [FPG] and postprandial glucose [PPG] area under the curve [AUC]) end points. RESULTS: Saxagliptin (2.5, 5, and 10 mg) plus metformin demonstrated statistically significant adjusted mean decreases from baseline to week 24 versus placebo in A1C (-0.59, -0.69, and -0.58 vs. +0.13%; all P < 0.0001), FPG (-14.31, -22.03, and -20.50 vs. +1.24 mg/dl; all P < 0.0001), and PPG AUC (-8,891, -9,586, and -8,137 vs. -3,291 mg · min/dl; all P < 0.0001). More than twice as many patients achieved A1C <7.0% with 2.5, 5, and 10 mg saxagliptin versus placebo (37, 44, and 44 vs. 17%; all P < 0.0001). β-Cell function and postprandial C-peptide, insulin, and glucagon AUCs improved in all saxagliptin treatment groups at week 24. Incidence of hypoglycemic adverse events and weight reductions were similar to those with placebo. CONCLUSIONS: Saxagliptin once daily added to metformin therapy was generally well tolerated and led to statistically significant improvements in glycemic indexes versus placebo added to metformin in patients with type 2 diabetes inadequately controlled with metformin alone.