The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone.
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.


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 > or =7.0 and < or =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). beta-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.
DeFronzo
Ralph A
RA
University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. albarado@uthscsa.edu
Hissa
Miguel N
MN
Garber
Alan J
AJ
Luiz Gross
Jorge
J
Yuyan Duan
Raina
R
Ravichandran
Shoba
S
Chen
Roland S
RS
D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004151:Dipeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D010919:Placebos; D016896:Treatment Outcome; D055815:Young Adult
D001786:Blood Glucose; D004151:Dipeptides; D007004:Hypoglycemic Agents; D010919:Placebos; D008687:Metformin; C502994:saxagliptin; D000218:Adamantane