Randomized trial of continuous subcutaneous delivery of exenatide by ITCA 650 versus twice-daily exenatide injections in metformin-treated type 2 diabetes.

Abstract

OBJECTIVE:

To evaluate ITCA 650, a continuous subcutaneous miniature osmotic pump delivery system of exenatide versus twice-daily exenatide injections (Ex-BID) in subjects with type 2 diabetes.

RESEARCH DESIGN AND METHODS:

We conducted a randomized, two-stage, 24-week, open-label, phase 2 study in type 2 diabetes inadequately controlled with metformin. Stage I: 155 subjects were randomized to 20 or 40 μg/day of ITCA 650 or Ex-BID 5 → 10 μg. Stage II: 131 subjects were rerandomized to 20, 40, 60, or 80 μg/day of ITCA 650. Change from baseline for HbA1c, weight, and fasting plasma glucose were evaluated at weeks 12 and 24.

RESULTS:

HbA1c was significantly lower in all groups after 12 and 24 weeks. Stage I: mean change in HbA1c from a mean baseline of 7.9-8.0% was -0.98, -0.95, and -0.72% for the 20 and 40 μg/day ITCA 650 and Ex-BID groups, respectively, with 63, 65, and 50% of subjects achieving HbA1c levels ≤ 7% (P < 0.05). Stage II: significant (P < 0.05) reductions in HbA1c (≈ 1.4% from baseline) were achieved with 60 and 80 μg/day ITCA 650, and 86 and 78% of subjects achieved HbA1c ≤ 7% at 24 weeks; respectively. Weight was reduced by 2.8-3.7 kg (P < 0.05) at 24 weeks in all except the 20 → 20 μg/day group. ITCA 650 was well tolerated; nausea was lower and transient with 20 μg/day relative to Ex-BID; and 60 μg/day had the best profile of tolerability and HbA1c lowering.

CONCLUSIONS:

ITCA 650 significantly reduced HbA1c and weight and was well tolerated. The 20 → 60 μg/day regimen was considered the best dose for further examination in phase 3.

• Authors: Robert R Henry, Julio Rosenstock, Douglas K Logan, Thomas R Alessi, Kenneth Luskey, Michelle A Baron
• Journal: Diabetes care (Diabetes Care) Vol. 36 Issue 9 Pg. 2559-65 (Sep 2013) ISSN: 1935-5548 [Electronic] United States
• PMID: 23645886 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Peptides
• Venoms
• Metformin
• Exenatide

Topics

• Adolescent
• Adult
• Aged
• Blood Glucose (drug effects)
• Body Weight (drug effects)
• Diabetes Mellitus, Type 2 (drug therapy)
• Exenatide
• Humans
• Hypoglycemic Agents (therapeutic use)
• Metformin (therapeutic use)
• Middle Aged
• Peptides (therapeutic use)
• Venoms (therapeutic use)
• Young Adult