Antisense Inhibition of Protein Tyrosine Phosphatase 1B With IONIS-PTP-1BRx Improves Insulin Sensitivity and Reduces Weight in Overweight Patients With Type 2 Diabetes
| Autor: | Lynnetta Watts, Erin S. Morgan, Nguyen C. Pham, Richard S. Geary, Sanjay Bhanot, Andres DiGenio, Shiangtung W. Jung, Brenda F. Baker |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.drug_class Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Type 2 diabetes Placebo 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Diabetes mellitus Internal medicine Multicenter trial Internal Medicine medicine Advanced and Specialized Nursing Adiponectin business.industry medicine.disease Sulfonylurea Metformin 030104 developmental biology Fructosamine Endocrinology chemistry business medicine.drug |
| Zdroj: | Diabetes Care. 41:807-814 |
| ISSN: | 1935-5548 0149-5992 |
| DOI: | 10.2337/dc17-2132 |
| Popis: | OBJECTIVE To evaluate safety and efficacy of IONIS-PTP-1BRx, a second-generation 2′-O-methoxyethyl antisense inhibitor of protein tyrosine phosphatase 1B, as add-on therapy in overweight patients with type 2 diabetes inadequately controlled with metformin with or without sulfonylurea therapy. RESEARCH DESIGN AND METHODS In this phase II, double-blind, randomized, placebo-controlled, multicenter trial, overweight and obese patients (BMI ≥27 kg/m2) with type 2 diabetes (HbA1c ≥7.5% [58 mmol/mol] and ≤10.5% [91 mmol/mol]) on a stable dose of metformin alone or with sulfonylurea were randomized 2:1 to IONIS-PTP-1BRx 200 mg (n = 62) or placebo (n = 30) once weekly for 26 weeks. RESULTS Mean baseline HbA1c was 8.6% (70 mmol/mol) and 8.7% (72 mmol/mol) in placebo and active treatment, respectively. At week 27, IONIS-PTP-1BRx reduced mean HbA1c levels by −0.44% (−4.8 mmol/mol; P = 0.074) from baseline and improved leptin (−4.4 ng/mL; P = 0.007) and adiponectin (0.99 μg/mL; P = 0.026) levels compared with placebo. By week 36, mean HbA1c was significantly reduced (−0.69% [−7.5 mmol/mol]; P = 0.034) and accompanied by reductions in fructosamine (−33.2 μmol/L; P = 0.005) and glycated albumin (−1.6%; P = 0.031) versus placebo. Despite both treatment groups receiving similar lifestyle counseling, mean body weight significantly decreased from baseline to week 27 with IONIS-PTP-1BRx versus placebo (−2.6 kg; P = 0.002) independent of HbA1c reduction (R2 = 0.0020). No safety concerns were identified in the study. CONCLUSIONS Compared with placebo, IONIS-PTP-1BRx treatment for 26 weeks produced prolonged reductions in HbA1c, improved medium-term glycemic parameters, reduced leptin and increased adiponectin levels, and resulted in a distinct body weight–reducing effect. |
| Databáze: | OpenAIRE |
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