Protein tyrosine phosphatase 1B (PTP1b) was first discovered in 1988. It is a counter-regulator to insulin and leptin signaling pathways. Given current endemic of insulin resistance via obesity and type 2 diabetes, it is natural to search for drugs that improve insulin and leptin sensitivities. PTP1b suppression is one of those options.
Here is a phase 2 clinical trial on an antisense inhibition of PTP1b (IONIS-PTP-1BRx). Results are promising but not profound: A1c and body weight dropped by 0.7% and 6 lbs in 27 to 36 weeks. No major adverse events were seen. A clearer picture of the drug will emerge in the future trials. At the same time the search for the other perfect PTP1b continues.
Insulin resistance related posts
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.
In this phase II, double-blind, randomized, placebo-controlled, multicenter trial, overweight and obese patients (BMI ≥27) with type 2 diabetes (HbA1c 7.5-10.5%) 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.
Mean baseline HbA1c was 8.6% and 8.7% in placebo and active treatment, respectively.
At week 27, IONIS-PTP-1BRx reduced mean HbA1c levels by −0.44% (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% (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.
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.