Abstract | BACKGROUND: OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of the dipeptidyl peptidase-4 inhibitor saxagliptin versus placebo as add-on therapy in patients with T2DM inadequately controlled with insulin alone or insulin plus metformin. METHODS: This was a long-term (28-week) extension of a short-term (24-week), randomized, double-blind, parallel-group trial of saxagliptin 5 mg once daily versus placebo as add-on therapy to open-label insulin or insulin plus metformin therapy totaling 52 weeks of treatment. In contrast with the goal of maintaining a stable insulin dosage during the short-term phase, during the extension phase the insulin dosage was flexible and adjusted as deemed appropriate by the investigator. The study was conducted in a clinical practice setting, including family practice and hospital sites. Patients with T2DM aged 18-78 years with glycated hemoglobin (HbA1c) 7.5-11 % on a stable insulin regimen (30-150 U/day with or without metformin) for ≥8 weeks at screening were included in the study. Patients were stratified by metformin use and randomly assigned 2:1 to oral saxagliptin 5 mg (n = 304) or placebo (n = 151) once daily. All patients who completed the initial 24 weeks of treatment were eligible to participate in the 28-week extension, regardless of whether they had required rescue treatment. The main outcome measure was change in HbA1c from baseline to week 52. RESULTS: In general, the outcomes achieved at week 24 were sustained to week 52. Adjusted mean change from baseline HbA1c at week 52 was greater with saxagliptin (-0.75 %) versus placebo (-0.38 %); the adjusted between-group difference was -0.37 % (95 % CI -0.55 to -0.19); between-group differences were similar in patients treated with metformin (-0.37 % [95 % CI -0.59 to -0.15]) and without metformin (-0.37 % [95 % CI -0.69 to -0.04]). At week 52, a greater proportion of patients receiving saxagliptin achieved HbA1c <7 % than those receiving placebo (21.3 vs. 8.7 %; between-group difference 12.6 % [95 % CI 6.1-19.1]). The increase from baseline in mean total daily insulin dose at week 52 was numerically smaller with saxagliptin (5.67 vs 6.67 U with placebo; difference, -1.01 U [95 % CI -3.24 to 1.22]). During the 52-week study period, the proportion of patients reporting ≥1 adverse event (AE) was 66.4 % with saxagliptin and 71.5 % with placebo, the majority being mild or moderate in intensity. The most common AEs (≥5 % with saxagliptin or placebo) were urinary tract infection, nasopharyngitis, upper respiratory tract infection, headache, influenza, and pain in extremity; the incidence of each AE was similar between treatment groups. In the saxagliptin and placebo groups, the incidence of reported hypoglycemia was 22.7 and 26.5 %, respectively; the incidence of confirmed hypoglycemia (fingerstick glucose ≤50 mg/dL [≤2.77 mmol/L] with characteristic symptoms) was 7.6 and 6.6 %, respectively. Adjusted mean change from baseline body weight was +0.8 kg with saxagliptin and +0.5 kg with placebo. CONCLUSION:
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Authors | Anthony H Barnett, Bernard Charbonnel, Jia Li, Mark Donovan, Douglas Fleming, Nayyar Iqbal |
Journal | Clinical drug investigation
(Clin Drug Investig)
Vol. 33
Issue 10
Pg. 707-17
(Oct 2013)
ISSN: 1179-1918 [Electronic] New Zealand |
PMID | 23949898
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Dipeptides
- Dipeptidyl-Peptidase IV Inhibitors
- Hypoglycemic Agents
- Insulin
- Metformin
- saxagliptin
- Adamantane
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Topics |
- Adamantane
(administration & dosage, adverse effects, analogs & derivatives)
- Adolescent
- Adult
- Aged
- Diabetes Mellitus, Type 2
(blood, drug therapy, epidemiology)
- Dipeptides
(administration & dosage, adverse effects)
- Dipeptidyl-Peptidase IV Inhibitors
(administration & dosage, adverse effects)
- Double-Blind Method
- Drug Therapy, Combination
- Female
- Headache
(chemically induced, diagnosis)
- Humans
- Hypoglycemic Agents
(administration & dosage, adverse effects)
- Insulin
(administration & dosage, adverse effects)
- Male
- Metformin
(administration & dosage, adverse effects)
- Middle Aged
- Time Factors
- Treatment Outcome
- Urinary Tract Infections
(chemically induced, diagnosis)
- Young Adult
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