肥胖不再是目标——系统才是：科学将其重新定义为多器官疾病-动脉网

Obesity Is No Longer the Target—It’s the System: Science Reframes It as a Multiorgan Disease

GeneOnline 等信源发布 2026-03-18 14:01

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by Bernice Lottering

伯尼斯·洛特林格

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As cardiometabolic research advances, therapies are shifting from weight-centric outcomes to organ-level disease modification, with emerging combinations such as GLP-1 and SGLT2 inhibitors demonstrating up to ~30% reductions in major cardiovascular and renal events, signaling a new era of integrated metabolic care.

随着心脏代谢研究的进展，治疗方向正从以体重为中心的结果转向器官层面的疾病修饰，新兴的联合疗法（如GLP-1和SGLT2抑制剂）显示出可将主要心血管和肾脏事件减少约30%，标志着综合代谢治疗新时代的到来。

Image: Shutterstock.

图片：Shutterstock。

hile the global market remains fixated on the “weight loss shot,” a strategic pivot is occurring within high-level research institutions and biopharma pipelines. The industry is transitioning from a focus on mass-market “pounds lost” to a sophisticated era of total metabolic restoration. This shift represents a move toward .

虽然全球市场仍然聚焦于“减肥针”，但高层研究机构和生物制药研发管线内部正在发生战略性转变。该行业正从关注大众市场的“减重”转向一个全面代谢恢复的复杂时代。这一转变代表了向...迈进的趋势。

treating obesity not as a singular condition

将肥胖症视为不仅仅是一种单一的状况

, but as the primary driver of a

，但作为主要驱动因素

Cardiovascular-Kidney-Metabolic (CKM) syndrome

心血管-肾脏-代谢（CKM）综合征

—a systemic pathophysiological entity where obesity, type 2 diabetes (T2D), chronic kidney disease (CKD), and cardiovascular disease (CVD) accelerate one another’s progression.

—一种系统性病理生理实体，其中肥胖、2型糖尿病（T2D）、慢性肾病（CKD）和心血管疾病（CVD）相互加速彼此的进展。

The Pathophysiology of Cardiometabolic Multimorbidity

心脏代谢多重疾病的病理生理学

The medical community is redefining obesity as the anchor of a

医学界正在重新定义肥胖作为...的锚点

“cardiometabolic multimorbidity” (CMM) cluster

“心代谢多病”（CMM）集群

. Clinical findings in 2025 indicate that the coexistence of two or more of these conditions compounds the

2025年的临床研究结果显示，同时存在两种或多种此类病症会加剧问题。

risk of sudden cardiac death (SCD)

猝死（SCD）风险

and multi-organ failure.

多器官功能衰竭。

A Unified Syndrome:

统一综合征：

Research from

研究来自

Harvard and Oxford

哈佛和牛津

suggests a

建议一个

bidirectional relationship

双向关系

where obesity drives heart failure (HF) through hemodynamic stress, while CKD accelerates vascular aging.

肥胖通过血流动力学压力导致心力衰竭（HF），而CKD加速血管老化。

Clinical Indicators:

临床指标：

Data shows that a

数据显示，一个

1 SD increase in BMI

BMI增加1个标准差

correlates with a 1.34-fold

与1.34倍相关

increased hazard

增加的危险性

of Heart Failure with Preserved Ejection Fraction (HFpEF). Furthermore, metabolic syndrome is now a

射血分数保留的心力衰竭（HFpEF）。此外，代谢综合征现在是

strong predictor of CKD development

CKD发展的强有力预测因子

, showing a 1.51 hazard ratio for renal decline.

，显示肾功能下降的风险比为1.51。

This shift means that “success” is no longer measured by the bathroom scale but by organ-specific health markers. For the healthcare system, it moves the needle from reactive treatment to proactive risk-stratification. Patients should expect future diagnostic panels to prioritize visceral fat monitoring and renal filtration rates over simple BMI.

这种转变意味着“成功”不再由体重秤来衡量，而是由特定器官的健康指标来决定。对于医疗系统而言，这将从被动治疗转变为积极的风险分层。患者应预期未来的诊断组合将优先考虑内脏脂肪监测和肾小球滤过率，而非单纯的BMI。

In the long term, this suggests a move toward “Precision Metabolism,” where therapy is dictated by which organ system—heart, kidney, or liver—is under the most metabolic duress..

从长远来看，这表明将朝着“精准代谢”方向发展，根据哪个器官系统（心脏、肾脏或肝脏）承受最大的代谢压力来决定治疗方案。

The Rise of “Triple-G” Agonists: The Retatrutide Frontier

“三重G”激动剂的崛起：雷塔鲁肽前沿

The most significant leap in current R&D is the evolution of single-target GLP-1s into “triple-acting” therapies. Leading this charge is Eli Lilly’s

当前研发中最显著的飞跃是单靶点GLP-1药物进化为“三重作用”疗法。引领这一潮流的是礼来公司。

Retatrutide

雷特鲁肽

, targeting GLP-1, GIP, and glucagon receptors.

，靶向GLP-1、GIP和胰高血糖素受体。

Clinical Efficacy:

临床疗效：

Phase 3 data from the

第三阶段数据来自

TRIUMPH-4 trial

TRIUMPH-4 试验

(reported late 2025) demonstrated a mean weight reduction of

（2025年底报告）显示平均体重减轻了

28.7%

at 68 weeks, significantly outperforming the ~15% seen in

在 68 周时，显著优于约 15% 的表现，

STEP-1 semaglutide trials

STEP-1 司美格鲁肽试验

。

Targeting the Liver:

靶向肝脏：

The glucagon component specifically addresses

胰高血糖素成分特别针对

Metabolic Dysfunction-Associated Steatohepatitis (MASH)

代谢功能障碍相关脂肪性肝炎 (MASH)

. Findings indicate a

。调查结果表明

liver fat reduction of up to 86%

肝脏脂肪减少多达86%

at 48 weeks, with 93% of patients achieving normalized liver fat levels.

在48周时，93%的患者达到了肝脏脂肪水平的正常化。

Functional Gains:

功能增益：

The trial met secondary endpoints for physical function, showing as much as a

试验达到了身体功能的次要终点，显示出多达

75.8% improvement in WOMAC knee pain scores

WOMAC膝关节疼痛评分提高了75.8%

。

The emergence of “Triple-G” agonists signifies the end of “one-size-fits-all” incretin therapy. As Retatrutide nears the market, the clinical focus will shift toward patients with advanced MASH or metabolic liver disease, creating a new sub-specialty of “Hepatometabolic Medicine.” Watch for future “head-to-head” trials comparing triple-agonists against bariatric surgery; 28.7% weight loss brings pharmaceutical intervention into direct competition with surgical outcomes, potentially disrupting the surgical device market permanently..

“三重G”激动剂的出现标志着“一刀切”肠促胰素疗法的终结。随着Retatrutide即将上市，临床焦点将转向晚期MASH或代谢性肝病患者，从而催生“肝代谢医学”这一新的亚专科。未来可能会出现将三重激动剂与减重手术进行“头对头”比较的试验；28.7%的体重减轻使药物干预直接与手术效果竞争，可能永久颠覆手术设备市场。

The SGLT2i + GLP-1 Synergy: The Cardiorenal Cornerstone

SGLT2i + GLP-1 协同作用：心脏肾脏的基石

While triple-agonists capture headlines,

虽然三重激动剂占据了头条新闻，

SGLT2 inhibitors

SGLT2抑制剂

(Sodium-Glucose Cotransporter-2 inhibitors) are targeted to become the foundational “organ-preservation” cornerstone of 2026.

(SGLT-2抑制剂) 将成为2026年“器官保护”的基础基石。

The Kidney Advantage:

肾脏优势：

A January 2026

2026年1月

comparative effectiveness study in JAMA Internal Medicine

JAMA内科医学中的比较有效性研究

found that initiating SGLT2i therapy was associated with a

发现开始SGLT2i治疗与以下情况相关：

19% lower 5-year risk

5年风险降低19%

of Chronic Kidney Disease (CKD) compared to GLP-1 initiation (6.7% vs. 8.2%).

慢性肾病（CKD）相比GLP-1起始治疗（6.7% vs. 8.2%）。

Synergistic Power:

协同力量：

New

新

meta-analyses of over one million participants

超过一百万名参与者的荟萃分析

(January 2026) show that combining SGLT2 inhibitors with GLP-1s leads to an approximately

（2026年1月）显示，将SGLT2抑制剂与GLP-1结合使用会导致大约

30% lower risk of major adverse cardiovascular and serious renal events than monotherapy.

主要不良心血管事件和严重肾脏事件的风险比单药治疗低30%。

Heart Failure Stability:

心力衰竭稳定性：

SGLT2 inhibitors provide a

SGLT2抑制剂提供了一种

consistent 25% reduction

持续减少25%

in cardiovascular death or heart failure hospitalization across the

心血管死亡或心力衰竭住院的情况

entire

整个的

ejection fraction spectrum, including the notoriously difficult-to-treat HFpEF.

射血分数谱，包括众所周知难以治疗的HFpEF。

We are entering the era of “Quadruple Therapy.” Clinical protocols in 2026 are shifting to recognize that GLP-1s manage the metabolic fuel (weight and insulin), while SGLT2s stabilize the hemodynamic pump and filter (heart and kidneys). For the patient, this means the future treatment plan is a dual-regimen designed for 360-degree protection.

我们正在进入“四联疗法”时代。2026年的临床方案将发生变化，承认GLP-1类药物管理代谢燃料（体重和胰岛素），而SGLT2类药物稳定血液动力泵和过滤器（心脏和肾脏）。对于患者而言，这意味着未来的治疗计划将是为实现360度保护而设计的双重方案。

Expect a market surge in fixed-dose combinations (pills containing both agents) to improve adherence in complex multimorbidity cases..

预计固定剂量组合（包含两种药物的药丸）市场将出现激增，以提高复杂多病症病例的依从性。

The “Muscle-Sparing” Mandate: Solving the Sarcopenia Problem

“肌肉保留”指令：解决肌肉减少症问题

In traditional GLP-1 therapy,

在传统的GLP-1疗法中，

33% to 35% of weight lost

体重减轻了33%到35%

can be lean muscle mass. Research from

可以是瘦肌肉质量。来自

Mass General Brigham

马萨诸塞州总医院布里格姆

is pioneering “combination biology” to prevent sarcopenic obesity.

正在开创“组合生物学”以预防肌肉减少性肥胖。

Myostatin Inhibition:

肌肉生长抑制素抑制：

Regeneron’s

再生元的

Phase 2 COURAGE trial

第二阶段勇气试验

(September 2025) combined semaglutide with

（2025年9月）将司美鲁肽与

trevogrumab

特雷沃单抗

。

The Findings:

调查结果：

This combination

这种组合

prevented approximately 50% of the lean mass loss

防止了大约50%的瘦体质量损失

typically seen in monotherapy while accelerating fat mass reduction.

通常在单药治疗中可见，同时加速脂肪量减少。

This “quality over quantity” approach will likely become the standard of care for geriatric populations. The financial implication is a significant reduction in long-term frailty-related healthcare costs (falls, hip fractures, and assisted living). For the patient, this means the future of weight loss isn’t just “smaller clothes,” but “stronger bodies.” We should anticipate a surge in “Dual-Action” prescriptions that combine a metabolic agonist with a muscle-retention biologic as the first-line defense against aging..

这种“质量优于数量”的方法可能会成为老年人群护理的标准。其经济影响是大幅减少与长期虚弱相关的医疗成本（如跌倒、髋部骨折和辅助生活）。对患者而言，这意味着减肥的未来不仅是“衣服变小”，而是“身体更强壮”。我们应该预见到“双重作用”处方的激增，这种处方会将代谢激动剂与保留肌肉的生物制剂相结合，作为对抗衰老的第一道防线。

Market and Economic Inference: The Specialty CDMO Surge

市场与经济推断：特种CDMO的激增

The shift to complex “antibody-peptide conjugates” is restructuring the

转向复杂的“抗体-肽偶联物”正在重组

Contract Development and Manufacturing Organization (CDMO) sector

合同开发和制造组织（CDMO）行业

, with the market projected to reach $392 billion by 2035.

，预计到2035年市场将达到3920亿美元。

The Complexity Squeeze:

复杂性挤压：

Complex modalities require

复杂模式需要

specialized sterile fill-finish facilities

专门的无菌填充设施

。

Investment Trends:

投资趋势：

AstraZeneca announced a

阿斯利康宣布

$2 billion biologics expansion

20亿美元的生物制品扩展

while GSK committed $1.2 billion to new facilities to secure supply chains for 2026 launches.

同时，GSK投入了12亿美元用于新设施，以确保2026年上市产品的供应链安全。

The “Biological Arms Race” means that manufacturing capacity—not just R&D—will dictate who wins the cardiometabolic market. For investors, this creates a significant opportunity in the sub-sectors of cold-chain logistics and high-tech bioreactor manufacturing. The real bottleneck to watch is the “Fill-Finish” capacity; if supply cannot meet the 2026 demand surge, we may see a tiered pricing system where only high-risk “multimorbidity” patients receive priority access to the newest triple-agonists..

“生物军备竞赛”意味着生产能力而不仅仅是研发将决定谁会赢得心血管代谢市场。对投资者而言，这在冷链物流和高科技生物反应器制造的子行业中创造了重大机会。真正的瓶颈在于“灌装-完成”能力；如果供应无法满足2026年需求激增，我们可能会看到分级定价体系，只有高风险的“多病共存”患者才能优先获得最新的三重激动剂药物。

Policy and Regulatory Pivot: The Value-Based Shift

政策与监管转向：基于价值的转变

A significant milestone occurred in late 2025 as the

2025年底，一个重要的里程碑出现了，

CMS proposed a reinterpretation

CMS提出了重新解释

of statutory exclusions for anti-obesity medications.

针对抗肥胖药物的法定排除情况。

Regulatory Redefinition:

监管重新定义：

For 2026,

对于2026年，

CMS allowed Medicare Part D coverage

CMS允许Medicare Part D覆盖

for AOMs, treating obesity as a

对于AOMs，将肥胖视为一种疾病

chronic disease requiring long-term management

需要长期管理的慢性疾病

。

Systemic Impact:

系统性影响：

This forces a move toward Value-Based Care, where the high cost of the drug is offset by avoiding $100,000 cardiovascular events or lifetime dialysis.

这促使人们向价值导向型医疗迈进，即通过避免10万美元的心血管事件或终身透析来抵消药物的高昂成本。

This is the “watershed moment” for metabolic health equity. By acknowledging obesity as a chronic driver of high-cost disease, regulators are finally aligning with the science. What this really means is a transition from “fee-for-service” (treating a heart attack after it happens) to “fee-for-outcomes” (preventing the attack via metabolic management).

这是代谢健康公平的“分水岭时刻”。通过承认肥胖是高成本疾病的慢性驱动因素，监管机构终于与科学达成一致。这实际上意味着从“按服务收费”（在心脏病发作后进行治疗）转变为“按结果收费”（通过代谢管理预防心脏病发作）。

Future policy changes to watch include the potential for “Outcome-Based Rebates,” where pharma companies only get paid if the patient achieves specific heart or kidney health targets..

未来需要关注的政策变化包括“基于结果的回扣”的可能性，即制药公司只有在患者达到特定的心脏或肾脏健康目标时才能获得报酬。

This science signals an end to the “yo-yo” era. Chronic disease management is becoming a biological correction. For the

这项科学标志着“悠悠球”时代的终结。慢性病管理正在变成一种生物学上的矫正。对于

one in two U.S. adults

每两名美国成年人中就有一人

with hypertension or those with undiagnosed MASH, these next-gen therapies offer a statistically proven path to reversing conditions previously considered irreversible

对于高血压患者或未确诊的MASH患者，这些下一代疗法提供了一条统计学上已被证实的路径，可以逆转以前被认为不可逆的病情。

The 2026 GLP-1 Patent Cliff: Generics, Global Competition, and the $100 Billion M&A Race

2026年GLP-1专利悬崖：仿制药、全球竞争与千亿美元并购竞赛

The $3 Trillion Cardiometabolic Crisis: Mapping the Global Burden of Obesity, Diabetes, and MASH

3万亿美元的心脏代谢危机：绘制全球肥胖、糖尿病和MASH的负担地图

Gut Microbiome Composition Predicts Long-term Cardiometabolic Health Outcomes in Diverse Urban Populations

肠道微生物组组成预测不同城市人群的长期心代谢健康结果

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Bernice Lottering