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 [F] Diseases Research  / PubMed Research Articles  /
Antisense Inhibition of Protein Tyrosine Phosphatase 1B With IONIS-PTP-1BRxImproves Insulin Sensitivity and Reduces Weight in Overweight Patients With Type 2 Diabetes.




Diabetes care Feb ; ()


Digenio A1; Pham NC2; Watts LM3; Morgan ES4; Jung SW5; Baker BF6; Geary RS7; Bhanot S8;

Author Information
  • 1Ionis Pharmaceuticals, Carlsbad, CA.
  • 2Ionis Pharmaceuticals, Carlsbad, CA.
  • 3Ionis Pharmaceuticals, Carlsbad, CA.
  • 4Ionis Pharmaceuticals, Carlsbad, CA.
  • 5Ionis Pharmaceuticals, Carlsbad, CA.
  • 6Ionis Pharmaceuticals, Carlsbad, CA.
  • 7Ionis Pharmaceuticals, Carlsbad, CA.
  • 8Ionis Pharmaceuticals, Carlsbad, CA sbhanot@ionisph.com.


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-1BRx200 mg (n= 62) or placebo (n= 30) once weekly for 26 weeks.

RESULTS: Mean baseline HbA1cwas 8.6% (70 mmol/mol) and 8.7% (72 mmol/mol) in placebo and active treatment, respectively. At week 27, IONIS-PTP-1BRxreduced mean HbA1clevels 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 HbA1cwas 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-1BRxversus placebo (-2.6 kg;P= 0.002) independent of HbA1creduction (R2= 0.0020). No safety concerns were identified in the study.

CONCLUSIONS: Compared with placebo, IONIS-PTP-1BRxtreatment 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.

© 2018 by the American Diabetes Association.




Publication Type: Journal Article

This article is licensed under the the National Library of Medicine License. It uses material from the PubMed National Library of Medicine Data.

Last Modified:   2016-03-27

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