Ionis Pharmaceuticals, Carlsbad, CA.
Ionis Pharmaceuticals, Carlsbad, CA
Diabetes Care. 2018 Apr;41(4):807-814. doi: 10.2337/dc17-2132. Epub 2018 Feb 9.
To evaluate safety and efficacy of IONIS-PTP-1B, a second-generation 2'--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 kg/m) with type 2 diabetes (HbA ≥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-1B 200 mg ( = 62) or placebo ( = 30) once weekly for 26 weeks.
Mean baseline HbA was 8.6% (70 mmol/mol) and 8.7% (72 mmol/mol) in placebo and active treatment, respectively. At week 27, IONIS-PTP-1B reduced mean HbA levels by -0.44% (-4.8 mmol/mol; = 0.074) from baseline and improved leptin (-4.4 ng/mL; = 0.007) and adiponectin (0.99 μg/mL; = 0.026) levels compared with placebo. By week 36, mean HbA was significantly reduced (-0.69% [-7.5 mmol/mol]; = 0.034) and accompanied by reductions in fructosamine (-33.2 μmol/L; = 0.005) and glycated albumin (-1.6%; = 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-1B versus placebo (-2.6 kg; = 0.002) independent of HbA reduction ( = 0.0020). No safety concerns were identified in the study.
Compared with placebo, IONIS-PTP-1B treatment for 26 weeks produced prolonged reductions in HbA, improved medium-term glycemic parameters, reduced leptin and increased adiponectin levels, and resulted in a distinct body weight-reducing effect.
评估 IONIS-PTP-1B 的安全性和疗效，IONIS-PTP-1B 是一种第二代 2'--甲氧基乙基蛋白酪氨酸磷酸酶 1B 反义抑制剂，作为二甲双胍联合或不联合磺酰脲类药物治疗血糖控制不佳的超重 2 型糖尿病患者的附加治疗药物。
在这项为期 26 周的、双盲、随机、安慰剂对照、多中心的 II 期临床试验中，BMI≥27kg/m2 的超重和肥胖（BMI≥27kg/m2）2 型糖尿病（HbA≥7.5%[58mmol/mol]且≤10.5%[91mmol/mol]）患者，接受稳定剂量的二甲双胍单药或联合磺酰脲类药物治疗，随机以 2:1 的比例分为 IONIS-PTP-1B 200mg（n=62）或安慰剂（n=30）组，每周一次，共 26 周。
安慰剂和活性治疗组的基线平均 HbA 分别为 8.6%（70mmol/mol）和 8.7%（72mmol/mol）。在第 27 周时，IONIS-PTP-1B 从基线降低了平均 HbA 水平 0.44%（-4.8mmol/mol； = 0.074），并改善了瘦素（-4.4ng/mL； = 0.007）和脂联素（0.99μg/mL； = 0.026）水平，与安慰剂相比。在第 36 周时，平均 HbA 显著降低（-0.69%[-7.5mmol/mol]； = 0.034），同时果糖胺（-33.2μmol/L； = 0.005）和糖化白蛋白（-1.6%； = 0.031）也降低。尽管两组患者都接受了类似的生活方式咨询，但与安慰剂相比，IONIS-PTP-1B 治疗 27 周后体重显著下降（2.6kg； = 0.002），与 HbA 降低无关（ = 0.0020）。研究中未发现安全性问题。
与安慰剂相比，IONIS-PTP-1B 治疗 26 周可显著降低 HbA，改善中期血糖参数，降低瘦素水平，升高脂联素水平，显著降低体重。
