Abstract | OBJECTIVE: RESEARCH DESIGN AND METHODS: This was a 24-week randomized, double-blind, placebo- and active-controlled study of 0.5-3.0 mg INT131 versus 45 mg pioglitazone or placebo daily in 367 subjects with T2D on sulfonylurea or sulfonylurea plus metformin. The primary efficacy analysis was the comparison of change from baseline to week 24 in hemoglobin A1c (HbA1c) across treatment groups. Fluid status was assessed with a prospective scoring system for lower-extremity pitting edema. RESULTS:
INT131 had a steep dose response for efficacy as measured by changes in HbA1c. After 24 weeks' treatment, the 0.5-mg dose demonstrated minimal efficacy (HbA1c -0.3 ± 0.12%) and the 2-mg dose demonstrated near-maximal efficacy (HbA1c -1.1 ± 0.12%), which was not statistically different from the efficacy of 45 mg pioglitazone (HbA1c -0.9 ± 0.12%; P < 0.01 for noninferiority). With the 1-mg dose, INT131 provided significant improvements in glycemic control (HbA1c 0.8 ± 0.12; P < 0.001 vs. placebo) but with less edema, weight gain, and hemodilution than observed with 45 mg pioglitazone. CONCLUSIONS:
INT131 demonstrated dose-dependent reductions in HbA1c, equivalent to 45 mg pioglitazone, but with less fluid accumulation and weight gain, consistent with its SPPARM design.
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Authors | Alex M DePaoli, Linda S Higgins, Robert R Henry, Christos Mantzoros, Fredrick L Dunn, INT131-007 Study Group |
Journal | Diabetes care
(Diabetes Care)
Vol. 37
Issue 7
Pg. 1918-23
(Jul 2014)
ISSN: 1935-5548 [Electronic] United States |
PMID | 24722496
(Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | © 2014 by the American Diabetes Association. |
Chemical References |
- Blood Glucose
- Glycated Hemoglobin A
- Hypoglycemic Agents
- INT 131
- PPAR gamma
- Quinolines
- Sulfonamides
- Sulfonylurea Compounds
- Thiazolidinediones
- Metformin
- Pioglitazone
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Topics |
- Adult
- Aged
- Blood Glucose
(drug effects)
- Diabetes Mellitus, Type 2
(drug therapy)
- Dose-Response Relationship, Drug
- Double-Blind Method
- Female
- Glycated Hemoglobin
(metabolism)
- Humans
- Hypoglycemic Agents
(adverse effects, pharmacology, therapeutic use)
- Male
- Metformin
(administration & dosage, therapeutic use)
- Middle Aged
- PPAR gamma
(agonists)
- Pioglitazone
- Prospective Studies
- Quinolines
(adverse effects, pharmacology, therapeutic use)
- Sulfonamides
(adverse effects, pharmacology, therapeutic use)
- Sulfonylurea Compounds
(therapeutic use)
- Thiazolidinediones
(adverse effects, therapeutic use)
- Treatment Outcome
- Weight Gain
(drug effects)
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