Saxagliptin and metformin XR combination therapy provides glycemic control over 24 hours in patients with T2DM inadequately controlled with metformin.
OBJECTIVE
To assess 24-hour glycemic control with saxagliptin compared with placebo as add-on treatment to metformin in patients with type 2 diabetes mellitus (T2DM) and inadequate glycemic control.


METHODS
This was a 4-week, multicenter, randomized, double-blind, placebo-controlled Phase IIIb trial comparing the antihyperglycemic activity of saxagliptin 5 mg once daily in combination with a stable dose of metformin extended release (XR) vs. placebo in combination with metformin XR in patients with T2DM inadequately controlled (screening glycated hemoglobin [HbA(1c)] 7-10%) with stable doses of metformin immediate release or metformin XR ≥ 1500 mg/day. Ninety-three adult patients were randomized and received treatment. The primary outcome measure was change from baseline to week 4 in 24-hour mean weighted glucose (MWG).


RESULTS
The reduction from baseline in 24-hour MWG was significantly greater for saxagliptin 5 mg + metformin XR (-13.8 mg/dL; -0.77 mmol/L) compared with placebo + metformin XR (3.0 mg/dL; 0.17 mmol/L) (p = 0.0001). At week 4, the mean decrease in plasma glucose was sustained through a 24-hour period in saxagliptin-treated patients. Treatment with saxagliptin 5 mg + metformin XR resulted in significant mean reductions from baseline in 4-hour mean weighted postprandial glucose (PPG), 2-hour PPG, 3-day average mean daily glucose, and fasting plasma glucose levels compared with placebo + metformin XR (p ≤ 0.001). The proportion of adverse events (AEs) was similar in the two treatment groups, with no reported hypoglycemic AEs in saxagliptin-treated patients. The 4-week evaluation period may have been insufficient to evaluate longer term effects on hyperglycemia or to identify additional AEs.


CONCLUSIONS
In patients with T2DM treated with metformin XR, saxagliptin 5 mg orally administered once daily in the evening for 4 weeks effectively lowered plasma glucose concentrations through the 24-hour dosing interval and was well tolerated.
Stenlöf
Kaj
K
Clinical Trial Center, Sahlgrenska University Hospital, Gothenburg, Sweden. kaj.stenlof@medfak.gu.se
Raz
Itamar
I
Neutel
Joel
J
Ravichandran
Shoba
S
Berglind
Niklas
N
Chen
Roland
R
D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004151:Dipeptides / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010919:Placebos; D017211:Treatment Failure; D016896:Treatment Outcome
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D004151:Dipeptides; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D010919:Placebos; D008687:Metformin; C502994:saxagliptin; D000218:Adamantane