Exendin-4 is a treatment for Type 2 Diabetes

继续Z01AG00905-04 LCI，我们获得了FDA的IND，用于研究糖尿病人的exendin-4。1998年12月，我们在非糖尿病（n=12）和糖尿病（n=12）受试者中开始了一项exendin-4 （RPN:GRC98-10-26-01）的急性研究，看看它是否具有(1)促胰岛素作用，(2)寿命长，(3)比GLP-1更有效，(4)在糖尿病状态下有效，(5)有效控制餐后血糖升高（由于第一阶段胰岛素分泌不足，这是2型糖尿病的一个主要问题）。我们发现所有五个方面都是如此（EASD '99: exendin-4在人类中的胰岛素促胰岛素作用，A148）。我们还发现exendin-4在非糖尿病和糖尿病患者中都具有胰岛素模拟作用（增加葡萄糖摄取）。这证实了我们在Z01AG00906-04 LCI中提出的假设，即GLP-1是胰岛素模拟物。使用更有效的exendin-4，我们可以清楚地阐明这一发现。随后，我们又启动了两项临床研究（RPN: GRC99-02-09-01和GRC99-07-07-01）。我们正在对2型糖尿病患者进行为期一个月的每日皮下注射exendin-4，并在治疗30天前后监测胰岛素分泌和葡萄糖摄取。为了证明exendin-4是一种真正的胰岛素模拟药物，我们将在1型糖尿病患者中进行exendin-4的急性研究。由于它们没有内源性胰岛素分泌，我们看到的对葡萄糖摄取的任何影响都应该是由于exendin-4的施用，而不是由于内源性胰岛素分泌。我们认为exendin-4或其正在开发的类似物之一将成为未来治疗糖尿病的方法。

Continuing Z01AG00905-04 LCI, we received an Investigators' IND from the FDA to study exendin-4 in diabetic humans. In December 1998, we started an acute study of exendin-4 (RPN:GRC98-10-26-01 in non-diabetic (n=12) and diabetic (n=12) subjects to see if it was (1) insulinotropic, (2) long-lived, (3) more potent than GLP-1, (4) effective in the diabetic state,and (5)effective in controlling post-prandial glucose elevations (which are a major problem in type 2 diabetes due to deficient first phase insulin secretion). We found all five aspects to be the case (EASD '99: Insulinotropic effect of exendin-4 in humans, A148). We also found that exendin-4 was insulinomimetic (increases glucose uptake) in both non-diabetic and diabetic humans. This confirms what we suspected as outlined in Z01AG00906-04 LCI in which we hypothesized GLP-1 was insulinomimetic. Using the more potent exendin-4, we could clearly elucidate this finding. Subsequently, we initiated two more clinical studies(RPN: GRC99-02-09-01 and GRC99-07-07-01). We are in the process of giving exendin-4 daily subcutaneously to type 2 diabetic subjects for up to one month, with measures of insulin secretion and glucose uptake monitored before and after the 30-day treatment. In order to prove that exendin-4 is a true insulinomimetic agent, we will carry out an acute study of exendin-4 in type 1 diabetic subjects. As they have no endogenous insulin secretion, any effect we see on glucose uptake should be due to the administration of exendin-4 and not due to endogenous insulin secretion. We think that exendin-4, or one of its analogs which are developing, will be future treatments for diabetes.