一石三鸟：瑞他鲁肽前途光明，马斯克减肥太猴急
来源：倍可亲(backchina.com) 专题：抄底还是跑路？美股最新动态
一石三鸟：瑞他鲁肽治疗肥胖症前途光明，马斯克减肥太猴急
倍可亲科学专题（Lily）
科学家累死累活做出了药物谁都不知道，名人带个货立马路人皆知。你知道索马鲁肽（Semaglutide）是个什么鬼吗？但你肯定知道大富豪埃隆·马斯克注射了一种药物，并秀了一把迅速消瘦的身材，那就是索马鲁肽，商品名叫司美格鲁肽（Wegovy）或诺和泰（Ozempic）。马斯克作秀在前，越来越多的人想步其后尘，希望通过药物来拯救肥胖的自己。
肥胖症患者与健康人不一样，他们体内荷尔蒙反应异常，对营养物质代谢异常。 肥胖者的细胞往往对胰岛素不太敏感，导致葡萄糖和脂肪酸不容易分解，堆在那儿。肥胖症者体内还会产生大量的“饥饿荷尔蒙”，让他们更容易暴饮暴食，让脂肪细胞进一步在腹部囤积，并更容易得糖尿病和高血压等疾病。 总之，肥胖症是一种慢性疾病，没法仅靠饮食控制或锻炼治愈。
肥胖人群通常三种重要激素都表现异常：胰高血糖素样肽1（GLP-1）、葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素（GCG），即“三G”。 GLP-1的主要作用就像“减糖剂”，它可以刺激胰岛素分泌并抑制胰高血糖素分泌，从而有效控制饭后血糖的峰值。 GCG 的作用类似于“升糖剂”，它的作用与胰岛素相反，使您的血糖升高而不是下降。 GIP 的功能相当于“脂肪管理器”，它可以抑制原有脂肪分解，并促进新的脂肪形成, 听起来像是肥胖者的噩梦。但GIP能让人产生饱胀感，没有胃口再乱吃东西。
因马斯克而名扬天下的索马鲁肽的工作原理是，它可以激活GLP-1受体，让身体在需要时产生更多胰岛素，停止释放 GCG（升糖剂），并抑制肝脏生成糖。 总之，索马鲁肽可以有效降低餐前和餐后的血糖水平。 索马鲁肽现已进入第三阶段试验，乃肥胖者的大大的福音。另一种肽分子替西帕肽（Tirzepatide），商品名为蒙扎罗(Mounjaro)，也进入了 3 期临床试验。它是 GLP-1 和 GIP 受体的“双重助手”，它使人体糖代谢更有效，并作用于大脑的某些区域以抑制食物摄入。NBA 明星查尔斯·巴克利 (Charles Barkley) 是公开承认服用替泽帕肽 (Tirzepatide) 的名人之一，他减掉了 60 多磅，效果相当惊人。
事实上，马斯克太猴急，完全可以等一段时间再减肥。肥胖克星之后起之秀瑞他鲁肽（Retatrutide）效果可能完爆马斯克用过的索马鲁肽！瑞他鲁肽是一种多肽，可以同时激活三种 G 受体（GLP-1、GIP 和 GCG）。 瑞他鲁肽的工作机制听起来有点奇怪：同时刺激“降糖剂”、“升糖剂”、和“脂肪管理器”有什么意义呢？ 然而事实证明，当激活三个 G 时，它的工作效率比仅激活一个或两个 G 时更有效。瑞他鲁肽自身激活“降糖剂”的活力要高于激活“升糖剂”的活力，而其他科学家也在动物实验中证实过，当“降糖剂”完全激活后，再添加一点“升糖剂”，反而更有利于消除体内的脂肪。
瑞他鲁肽的二期临床实验由Jastreboff 等人合作完成，结果发表在2023 年 8 月 10 日N ENGL J MED 389;6 nejm.org 上，标题是“Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial”。 在这项临床实验中，参与者每周一次皮下注射不同剂量的瑞他鲁肽或安慰剂。 24 周后，研究者发现瑞他鲁肽可将肥胖个体的体重大幅减轻 7.2% 至 17.5%。 当试验时间延长至48周时，瑞他鲁肽的疗效更加明显，参加者的体重下降了8.7%至24.2%。注射剂量越高，减肥效果越好，而安慰剂组在 24 周和 48 周时仅分别下降了 1.6% 和 2.1%。
使用瑞他鲁肽有轻度至中度的不良反应，主要表现为胃肠道症状，如恶心、腹泻、呕吐和便秘，剂量越高不良反应越重。 此外，少数参与者在 24 周时有心率升高现象。 但随着药物应用持续 36 周和 48 周，这些增加的心率都恢复到了正常水平。
鉴于瑞他鲁肽的第二阶段临床试验已经成功，应该有望马上进入第三期临床实验。 第三期临床实验将选用更多的参与者，并涵盖更广泛的人种（第二阶期的参与者大部分是白种人）。 三期临床实验旨在全面评估瑞他鲁肽的最佳剂量、治疗持续时间和长期使用的安全性。
作为这个药物将来的潜在的受益者，您也许有点好奇，自己有必要用药物来减肥吗？以下是二期临床试验参与者的选择标准：
1.年龄在18岁至75岁之间。
2. 身体质量指数（BMI，体重公斤数除以身高米的平方）在30至50之间。
3. 如果BMI 在27 至 30之间，但有一种或一种以上肥胖相关的状况，如腰围 > 100 厘米、前期糖尿病、高血压或血脂异常，也符合参与标准。
如果您未能达到参与标准，恭喜您！您多半不需要为自己圆乎乎的脸蛋或略显丰满的身材担心。少吃多动就可以了！
One stone three birds: Retatrutide looks more promising than what Elon Musk used in treating obesity
BackChina Science (Lily)
Scientists toil and strive to develop medicines, unknown to the masses, while celebrities instantly make products widely known. Do you know what Semaglutide is? But you surely know that the billionaire Elon Musk injected an appetite suppressant and showcased a rapidly slimmed-down physique – that's Semaglutide, whose market name is Wegovy or Ozempic. With Musk's demonstration in the forefront, an increasing number of people are eager to follow suit, hoping to rescue their own obesity through medication.
Obese individuals normally have abnormal hormone responses to nutrient intake, which results in metabolic dysfunction. Consequently, their cells become less responsive to insulin's actions, their glucose and fatty acid refuse to break down, their “hunger hormones” keep them over-eating all the time, their fat cells are easier to accumulate around their belly, and they are easier to develop diseases such as diabetes and hypertension. In a nutshell, obesity is a kind of chronic disease which is not easy to cure by mere diet or working out.
There are three important hormones that are abnormally regulated in obese individuals: glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon (GCG), the three Gs. The main actions of GLP-1 is like a “sugar reducer”. It can stimulate insulin secretion and inhibit glucagon secretion, thereby helping to control the spikes in blood sugar after eating. GCG works like a "sugar booster" and it does the opposite of insulin, making your blood sugar go up instead of down. GIP functions as a "fat manager". It affects how your body deals with fats by stopping the breakdown of fats and encouraging the creation of new fats, sounding like a nightmare for obese, but it also stimulates satiety and makes you have less appetite in eating.
Semaglutide, the renowned worldwide chemical thanks to Musk, can activate GLP-1 receptors, helping the body to release more insulin when needed, stopping the release of GCG (the sugar booster), and decreasing the production of sugar by the liver. In conclusion, Semaglutide can effectively reduce blood glucose levels before and after meals. Semaglutide is already in phase 3 trials now and really a blessing for the obese. Another peptide molecule in phase 3 trial is Tirzepatide, whose brand name is Mounjaro, acts as a “dual helper” on both GLP-1 and GIP receptors. It makes the body's natural sugar-regulating system work better and acts on certain regions of the brain to suppress food intake. NBA icon Charles Barkley is among the celebrities who openly acknowledged their utilization of Tirzepatide, leading to a remarkable weight loss of over 60 pounds.
In fact, Musk could wait for a while before losing weight with Semaglutide. The new rising star in combating obesity, Retatrutide, might outperform the effects of Semaglutide! Retatrutide is a peptide that can activate all three G receptors (GLP-1, GIP , and GCG). The working mechanism of Retatrutide sounds a little strange: what is the point to stimulate the “sugar reducer”，the “sugar booster”, and the “fat manager” at the same time? However, it works more efficiently when three Gs are activated than only one or two Gs are activated. Retatrutide is much more potent at activating the “sugar reducer” than the “sugar booster”. Other scientists have also proved on animal experiments that when the “sugar reducer” was fully activated, adding some stimulation of the “sugar booster” will help to burn the body fat better.
The exciting results from Jastreboff etc, was published on N ENGL J MED 389;6 nejm.org August 10, 2023, titled "Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial". In this research, Retatrutide or placebo in different doses was injected under the participants‘skins once every week. After 24 weeks, Retatrutide was found to substantially reduce the body weight of obese individuals by 7.2% to 17.5%. With trial time extended to 48 weeks, the efficacy of Retatrutide worked even better that the body weight of the attended individuals decreased 8.7% to 24.2%. The reduction was dose related. The higher the dose, the better the weight-losing effects. The body weights of the placebo group only reduced 1.6% and 2.1%, at 24 and 48 weeks, respectively.
The adverse events associated with Retatrutide were generally mild to moderate, primarily as gastrointestinal symptoms such as nausea, diarrhea, vomiting, and constipation. These effects were observed to be dose-dependent. Additionally, a minority of participants experienced elevated heart rates at 24 weeks; however, the heart rates reverted to normal levels as the medication application continued through the 36- and 48-week periods.
Given the marked success of the phase 2 trial involving Retatrutide, there is a prospective advancement into the upcoming Phase 3 stage. This pivotal phase will involve a larger and more diverse population encompassing a wider range of racial and geographic backgrounds. Notably, the phase 2 trial predominantly enrolled individuals of white ethnicity. The Phase 3 trial aims to comprehensively assess the optimal dosage, treatment duration, and long-term safety profile of Retatrutide.
As a potential future beneficiary of this medication, you might be a bit curious whether it's necessary for you to use it for weight loss. Below are the selection criteria for participants in the Phase 2 clinical trial:
1. Age between 18 to 75 years.
2. Body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 30 to 50.
3. 27 100 cm, prediabetes, hypertension, or dyslipidemia.
If you fail to meet the criteria, congratulations! Largely, you don’t need to worry about your chubby face or somewhat plump figure. Just eat less and move more!
