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    一個由美國、中國、德國等國研究人員組成的科研小組10月30日在美國期刊《科學(xué)-轉(zhuǎn)化醫(yī)學(xué)》上報告說，動物及人類臨床試驗表明，可激活兩種內(nèi)分泌激素的一種人工合成分子能緩解糖尿病患者的血糖水平并有效降低體重。
 

    該科研小組當(dāng)天此前許多激素療法只能激活某個單一激素，不但需要大劑量治療才可見效，還往往帶來嚴(yán)重惡心等副作用。他們研制的合成分子，可同時激活對機體代謝調(diào)節(jié)起重要作用的GLP-1與GIP這兩種激素。

    研究人員首先針對患糖尿病的肥胖老鼠及猴子進行治療試驗。結(jié)果發(fā)現(xiàn)，這種合成分子比現(xiàn)有藥物更能有效降低體重并改善血糖。

    在為期6周的臨床試驗中，研究人員給53名患糖尿病的肥胖患者使用以這種分子制成的藥物。與未經(jīng)治療者相比，接受治療的患者可分泌更多胰島素，其血糖水平及肥胖問題均得到改善。盡管有些患者感到惡心，但沒有觀察到嚴(yán)重副作用。

    報告作者們認(rèn)為，他們研制的新分子或許是治療糖尿病及肥胖癥的新選擇。

    原文閱讀：Unimolecular Dual Incretins Maximize Metabolic Benefits in Rodents, Monkeys, and Humans

    Abstract

    We report the discovery and translational therapeutic efficacy of a peptide with potent, balanced co-agonism at both of the receptors for the incretin hormones glucagon-like peptide-1 （GLP-1） and glucose-dependent insulinotropic polypeptide （GIP）。 This unimolecular dual incretin is derived from an intermixed sequence of GLP-1 and GIP, and demonstrated enhanced antihyperglycemic and insulinotropic efficacy relative to selective GLP-1 agonists. Notably, this superior efficacy translated across rodent models of obesity and diabetes, including db/db mice and ** rats, to primates （cynomolgus monkeys and humans）。 Furthermore, this co-agonist exhibited synergism in reducing fat mass in obese rodents, whereas a selective GIP agonist demonstrated negligible weight-lowering efficacy. The unimolecular dual incretins corrected two causal mechanisms of diabesity, adiposity-induced insulin resistance and pancreatic insulin deficiency, more effectively than did selective mono-agonists. The duration of action of the unimolecular dual incretins was refined through site-specific lipidation or PEGylation to support less frequent administration. These peptides provide comparable pharmacology to the native peptides and enhanced efficacy relative to similarly modified selective GLP-1 agonists. The pharmacokinetic enhancement lessened peak drug exposure and, in combination with less dependence on GLP-1–mediated pharmacology, avoided the adverse gastrointestinal effects that typify selective GLP-1–based agonists. This discovery and validation of a balanced and high-potency dual incretin agonist enables a more physiological approach to management of diseases associated with impaired glucose tolerance.