Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin.
OBJECTIVE
To evaluate efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes (T2D) with inadequate glycemic control on insulin alone or combined with metformin.


METHODS
Adults (n = 455) with HbA(1c) 7.5-11% on stable insulin therapy (30-150 U/day ± metformin) for at least 8 weeks were stratified by metformin use and randomly assigned 2:1 to receive saxagliptin 5 mg or placebo once daily for 24 weeks. Patients were to maintain stable insulin doses but these could be decreased to reduce risk of hypoglycemia. Patients with hyperglycemia or substantially increased insulin use were rescued with a flexible insulin regimen and remained in the study. Metformin doses were kept stable. The primary efficacy endpoint was change in HbA(1c) from baseline to week 24 (or rescue).


RESULTS
Patients treated with saxagliptin versus placebo had significantly greater reductions in adjusted mean HbA(1c) (difference: -0.41%, p < 0.0001), postprandial glucose (PPG) 180-minute area under the curve (-3829.8 mg·min/dL, p = 0.0011), and 120-minute PPG (-23.0 mg/dL, p = 0.0016) at 24 weeks. Treatment with saxagliptin resulted in similar reductions in HBA(1c) relative to placebo, irrespective of metformin treatment. At 24 weeks, difference in adjusted mean fasting plasma glucose for saxagliptin versus placebo was -4.02 mg/dL (p = 0.3958); 17.3% and 6.7% of patients in the saxagliptin and placebo groups, respectively, achieved HbA(1c) < 7%. Mean change from baseline in body weight at week 24 was 0.39 kg for saxagliptin and 0.18 kg for placebo. Hypoglycemia was reported in 18.4% and 19.9% of patients in the saxagliptin and placebo groups, respectively (confirmed hypoglycemia: 5.3%, 3.3%). Other adverse events reported in at least 5% of patients were urinary tract infection (saxagliptin, placebo: 5.9%, 6.0%), influenza (3.0%, 6.6%), and pain in extremity (1.6%, 6.0%).


CONCLUSIONS
Saxagliptin 5-mg once-daily add-on therapy improves glycemic control in T2D patients on insulin alone or combined with metformin and is generally well-tolerated. NCT00757588.
University of Birmingham and BioMedical Research Centre, Heart of England National Health Service Foundation Trust, Birmingham, UK. anthony.barnett@heartofengland.nhs.uk
Anthony H
AH
Barnett
Bernard
B
Charbonnel
Mark
M
Donovan
Douglas
D
Fleming
Roland
R
Chen
D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004151:Dipeptides / Q000008:administration & dosage* / Q000009:adverse effects; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged
D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; C502994:saxagliptin; D000218:Adamantane