The short version of Dual agonist fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2026-05-06. Anything still debated is marked as such rather than presented as settled.
The peptide backbone contains 39 amino acids and includes alpha-aminoisobutyric acid residues, which are not among the standard proteinogenic set. A C20 fatty diacid moiety is attached through a linker, allowing the compound to bind serum albumin and extend its circulation time. This albumin binding is the main reason the molecule supports once-weekly administration rather than more frequent dosing. The measured molecular mass is approximately 4,813 daltons, placing it firmly in the peptide rather than small-molecule class.
Tirzepatide is a synthetic peptide that activates both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. This dual agonist profile distinguishes it from earlier incretin-based compounds that act on a single receptor. The molecule was engineered from the native GIP sequence and carries several non-natural residues that slow enzymatic breakdown. Researchers designed it to combine the insulinotropic effects of GIP signaling with the appetite and gastric-emptying effects associated with GLP-1 activation.
Development of tirzepatide took place under a research program that sought to test whether simultaneous engagement of two incretin receptors would produce greater metabolic effects than single-receptor agonism. Clinical trials were organized into the SURPASS series for type 2 diabetes and the SURMOUNT series for obesity and weight management. Regulatory clearance for type 2 diabetes came in 2022 in the United States, followed by approval for chronic weight management in 2023. The trial programs reported reductions in glycated hemoglobin and body weight relative to comparators, though long-term cardiovascular and durability data continue to accumulate.
脂肪酸侧链的存在使该肽与血浆白蛋白结合能力增强，从而延长循环半衰期，支持每周一次给药的用药间隔。白蛋白结合同时改变组织分布特征，减慢肾脏清除速度。该设计思路在多种长效肽类药物中被反复采用，属于既定的药代动力学策略。
该化合物的名称与结构由国际非专利名称体系统一维持，不同文献中出现的同义写法主要在拼写顺序或盐形式描述上不同。研究者通常通过受体结合实验、细胞内环磷酸腺苷积累测定以及动物模型来确认其双激动活性。相当一部分分子层面的细节——例如两条受体通路之间的信号交叉作用——尚处于开放问题状态。
| Property | Value | Notes |
|---|---|---|
| Molecular class | Modified synthetic peptide | 39-residue backbone with non-natural residues |
| Receptor targets | GIP and GLP-1 | Dual incretin receptor agonist |
| Approximate molecular mass | 4,813 Da | Calculated from the peptide sequence |
| Administration route | Subcutaneous injection | Weekly schedule in approved products |
| Albumin binding | Present | Mediated by a C20 fatty diacid side chain |
At the receptor level, the compound binds both GIP and GLP-1 receptors and triggers downstream signalling that raises cyclic AMP in target cells. GLP-1 receptor activation is associated with glucose-dependent insulin release, slower gastric emptying, and reduced appetite signalling. GIP receptor activation contributes effects that are less completely characterised, and how much each receptor adds to the overall clinical response is still an open question. The two pathways appear to interact in a complementary rather than a purely additive way.
An extended fatty diacid moiety promotes binding to serum albumin, which slows renal clearance and extends the circulating half-life to roughly five days. That property supports once-weekly administration and largely explains the dosing interval described in clinical reports. Published data come mainly from large randomised programmes that evaluated glycaemic control and body weight over periods of many months. Long-term outcomes beyond those trial windows, including what happens after treatment stops, remain an active area of investigation.
Tirzepatide is a synthetic peptide built from thirty-nine amino acids. Its sequence is derived from native glucose-dependent insulinotropic polypeptide, or GIP, with several non-natural residues and a fatty diacid side chain attached through a linker. The molecule behaves as a dual agonist at two incretin receptors, GIP and GLP-1, instead of targeting a single receptor. This dual engagement separates it from earlier single-receptor incretin compounds and underpins most of its reported pharmacological activity.
Reported outcomes in large trials include dose-dependent weight reduction and improvements in glycemic markers over periods ranging from several months to more than a year. Whether the compound alters long-term cardiovascular or renal outcomes is being examined in dedicated outcome studies, so those questions remain open. Labeling describes gastrointestinal effects such as nausea and diarrhea, which tend to appear during dose escalation. Discontinuation rates and the durability of effects after treatment stops vary across study populations and are still debated.
Tirzepatide is a synthetic peptide developed as a dual agonist at the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors. Its structure is built on a GIP-derived backbone with non-natural amino acid substitutions and a fatty diacid side chain that promotes albumin binding and slows clearance. That modification supports once-weekly subcutaneous dosing. Registrational trial programs reported reductions in body weight and glycated hemoglobin alongside the drug's glycemic effects.
=== Third-generation === Third generation antipsychotics are recognized as demonstrating D2 receptor partial agonism as opposed to the D2 and 5HT-2A receptor antagonism of second-generation (atypical) antipsychotics and D2 antagonism of first-generation (typical) antipsychotics.
=== Transplant === While dietary therapy has been shown to be effective to normalize the very-long chain fatty acid concentrations in the plasma of individuals with ALD, allogeneic hematopoietic stem cell transplants is the only treatment that can stop demyelination that is the hallmark of the cerebral forms of the disease. In order to be effective, the transplant must be done at an early stage of the disease; if the demyelination has progressed, transplant can worsen the outcome, and increase the rate of decline. While transplants have been shown to be effective at halting the demyelination process in those presenting with the childhood cerebral form of ALD, follow-up of these patients has shown that it does not improve adrenal function.
== Disease and serpinopathies == Serpins are involved in a wide array of physiological functions, and so mutations in genes encoding them can cause a range of diseases. Mutations that change the activity, specificity or aggregation properties of serpins all affect how they function. The majority of serpin-related diseases are the result of serpin polymerisation into aggregates, though several other types of disease-linked mutations also occur. The disorder alpha-1 antitrypsin deficiency is one of the most common hereditary diseases.
An adult's trachea has an inner diameter of about 1.5 to 2 centimetres (1⁄2 to 3⁄4 in) and a length of about 10 to 11 cm (4 to 4+1⁄4 in), wider in males than females. The trachea begins at the lower edge of the cricoid cartilage of the larynx at the level of sixth cervical vertebra (C6) and ends at the carina, the point where the trachea branches into left and right main bronchi., at the level of the fourth thoracic vertebra (T4), although its position may change with breathing. The trachea is surrounded by 16–20 rings of hyaline cartilage; these 'rings' are 4 millimetres high in the adult, incomplete and C-shaped. Ligaments connect the rings. The trachealis muscle connects the ends of the incomplete rings and runs along the back wall of the trachea. Also adventitia, which is the outermost layer of connective tissue that surrounds the hyaline cartilage, contributes to the trachea's ability to bend and stretch with movement. Although trachea is a midline structure, it can be displaced normally to the right by the aortic arch.
== N == David Nachmansohn (1899–1983). German biochemist at Columbia, responsible for elucidating the role of phosphocreatine in energy production in muscles. Member Natl. Acad. Sci. USA Joseph Needham FRS (1900–1995). British biochemist at Cambridge, historian and sinologist, noted for embryology and morphogenesis, and also in Chinese science. Eva J. Neer (1937–2000). American physician and biochemist at Harvard, who researched on G-protein cell biology. Member of the National Academy of Medicine. Joe Neilands (1921–2008). Canadian-born American biochemist and political activist at UC Berkeley, known for studies of microbial iron transport, and as author, with Paul K. Stumpf of Outlines of Enzyme Chemistry. Carl Neuberg (1877–1956). German biochemist at the University of Berlin, a pioneer in the study of metabolism. Michael Neuberger (1953–2013). British biochemist and immunologist at Cambridge University known for delineating the role of DNA deamination in immunity. Hans Neurath (1909–2002). American protein chemist at the University of Washington. He was the Founding editor of Biochemistry, which he edited for 30 years (1961–1991). Member Natl. Acad. Sci. USA. Eric Newsholme (1935–2011). British biochemist at the University of Oxford who specialised in human metabolism. Hermann Niemeyer (1918–1991). Chilean biochemist. National Prize of Science (Chile). Member of the Academy of Science of Chile. Marshall Warren Nirenberg (1927–2010).
Sources: en.wikipedia.org
Double-decker bus The approximate volume of a double-decker bus, abbreviated to DDB, has been used informally to describe the size of hole created by a major sewer collapse. For example, a report might refer to "a 4 DDB hole". Olympic-size swimming pool For larger volumes of liquid, one measure commonly used in the media in many countries is the Olympic-size swimming pool. A 50 m × 25 m (164 ft × 82 ft) Olympic swimming pool, built to the FR3 minimum depth of 2 metres (6.6 ft) would hold 2,500 m3 (660,000 US gal). The US National Institute of Standards and Technology (NIST) defines the Olympic swimming pool as 1 million litres, which is the approximate volume of the smaller FR2 pool. Royal Albert Hall The Royal Albert Hall, a large concert hall, is sometimes used as a unit of volume in the UK, for example when referring to volumes of rubbish placed in landfill. It is famously used in the line "Now they know how many holes it takes to fill the Albert Hall." in The Beatles song "A Day in the Life". The volume of the auditorium is between 3 and 3.5 million cubic feet (between 85,000 and 99,000 cubic metres). Melbourne Cricket Ground A common measure of volume in Australia, and in the state of Victoria in particular, is the Melbourne Cricket Ground, the largest stadium in Australia and 13th largest in the world. The volume of the Melbourne Cricket Ground is 1,574,000 cubic metres, or about 630 Olympic swimming pools. Its seating capacity (100,000 as of July 2019) is also used as a unit measure of the number of people.
One NADH molecule is produced by the enzyme glutamate dehydrogenase in the conversion of glutamate to ammonium and α-ketoglutarate. Glutamate is the non-toxic carrier of amine groups. This provides the ammonium ion used in the initial synthesis of carbamoyl phosphate. The fumarate released in the cytosol is hydrated to malate by cytosolic fumarase. This malate is then oxidized to oxaloacetate by cytosolic malate dehydrogenase, generating a reduced NADH in the cytosol. Oxaloacetate is one of the keto acids preferred by transaminases, and so will be recycled to aspartate, maintaining the flow of nitrogen into the urea cycle. We can summarize this by combining the reactions:
1993/29) Income Support (General) Amendment Regulations 1993 (S.I. 1993/30) Motor Vehicles (Wearing of Seat Belts by Children in Front Seats) Regulations 1993 (S.I. 1993/31) Food Protection (Emergency Prohibitions) (Radioactivity in Sheep) (Wales) (Partial Revocation) Order 1993 (S.I. 1993/32) Food Protection (Emergency Prohibitions) (Radioactivity in Sheep) (England) (Partial Revocation) Order 1993 (S.I. 1993/33) North West London Mental Health National Health Service Trust (Establishment) Order 1993 (S.I. 1993/34) Road Traffic Regulation Act 1984 (Amendment) Order 1993 (S.I. 1993/35) Local Authorities (Discretionary Expenditure) (Relevant Population) Regulations 1993 (S.I. 1993/40) Local Authorities (Discretionary Expenditure Limits) Order 1993 (S.I. 1993/41) Control of Pollution (Anglers' Lead Weights) (Amendment) Regulations 1993 (S.I. 1993/49) Gipsy Encampments (London Borough of Bromley) Order 1993 (S.I. 1993/50) Licensed Betting Offices (Amendment) Regulations 1993 (S.I. 1993/51) Combined Probation Areas (Powys) Order 1993 (S.I. 1993/52) National Rivers Authority (Anglian Region) (Reconstitution of the Alford Drainage Board) Order 1992 S.I. 1993/53) National Rivers Authority (Anglian Region) (Reconstruction of the North East Lindsey Internal Drainage Board) Order 1992 S.I. 1993/54) National Rivers Authority (Anglian Region) (Reconstitution of the Louth Drainage Board) Order 1992 S.I. 1993/55) Education (Higher Education Corporations) (Wales) (No. 3) Order 1993 (S.I. 1993/56) Friendly Societies (Group Schemes) Regulations 1993 (S.I.
=== Synthetic alizarin 1868 – 1873 === The development of synthetic alizarin opened up a huge market that was formerly served by natural dye makers. Alizarin was the first dye whose structure chemist determined, and they quickly set it as a target of synthesis, succeeding by 1868. Other chemical components of natural madder were identified and applied by the mid-19th century, including purpurin, which produced a delicate lilac colour, and green alizarin, which was patented in Britain and famously displayed at the 1867 Paris International Exhibition. Similar to aniline dyes, the precursors for Synthetic Alizarin were easily obtainable from coal tar. Germany dominated the synthetic alizarin market, however foreign competition was not non-extant, for example the British Alizarine Company Ltd.
Sources: en.wikipedia.org
== Criticism == Critics, such as Drug Free America Foundation and other members of network International Task Force on Strategic Drug Policy, state that a risk posed by harm reduction is by creating the perception that certain behaviours can be partaken of safely, such as illicit drug use, that it may lead to an increase in that behaviour by people who would otherwise be deterred. The signatories of the drug prohibitionist network International Task Force on Strategic Drug Policy stated that they oppose drug use harm reduction "...strategies as endpoints that promote the false notion that there are safe or responsible ways to use drugs. That is, strategies in which the primary goal is to enable drug users to maintain addictive, destructive, and compulsive behavior by misleading users about some drug risks while ignoring others." In 2008, the World Federation Against Drugs stated that while "...some organizations and local governments actively advocate the legalization of drugs and promote policies such as "harm reduction" that accept drug use and do not help people who use substances to become free from substance use. This undermines the international efforts to limit the supply of and demand for drugs." The Federation states that harm reduction efforts often end up being "drug legalization or other inappropriate relaxation efforts, a policy approach that violates the UN Conventions." Critics furthermore reject harm reduction measures for allegedly trying to establish certain forms of drug use as acceptable in society.
== Research == The steroidal antiandrogen cyproterone acetate has been studied for blocking the testosterone flare at the start of buserelin therapy in men with prostate cancer. While cyproterone acetate for two weeks eliminates the biological and biochemical signs of the flare, no benefits on prostate cancer outcomes were observed. Very low doses of buserelin nasal spray have been assessed for increasing testosterone levels and fertility in men with oligoasthenozoospermia and hypogonadotropic hypogonadism.
There is no one specific uniform cuisine of the Han Chinese since the culinary traditions and food consumed varies from Sichuan's famously spicy food to Guangdong's dim sum and fresh seafood. Analyses throughout the reaches of Northern and Southern China have revealed their main staple to be rice (more likely to consumed by southerners) as well as noodles and other wheat-based food items (which are more likely to be eaten by northerners). During China's Neolithic period, southwestern rice growers transitioned to millet from the northwest, when they could not find a suitable northwestern ecology—which was typically dry and cold—to sustain the generous yields of their staple as well as it did in other areas, such as along the eastern Chinese coast.
Developing standards-based messaging, to allow for automated data exchange Creating an exchange network, to ensure specific laboratories receive the information most pertinent to their work Improving reporting capabilities Selection and implementation of the best information management system for the laboratory's needs Strengthening the information network by sharing technical resources across public health laboratories One effort by the Informatics program is PHLIP, the Public Health Laboratory Interoperability Project. PHLIP aims to establish reliable laboratory data exchange between state public health laboratories and the CDC by fostering collaboration in IT and laboratory science.
==== Original attempt – Gorin ==== In 1974, French film-maker Jean-Pierre Gorin commissioned Dick to write a screenplay based on Ubik. Dick completed the screenplay within a month, but Gorin never filmed it. The screenplay was published as Ubik: The Screenplay in 1985 (ISBN 978-0911169065) and again in 2008 (ISBN 9781596061699). Dick's former wife Tessa claims that the published screenplay "has been heavily edited, and others have added material to the screenplay that Phil wrote", though she suggests that "film producers really ought to take a look at the author's own screenplay before embarking upon their journey of interpretation".
Sources: en.wikipedia.org
It binds and activates both the GIP and GLP-1 receptors, making it a dual incretin receptor agonist. Single-receptor GLP-1 agonists act on one target only. The dual profile is the defining pharmacological feature of the molecule.
A fatty diacid side chain promotes reversible binding to serum albumin. This association slows renal clearance and protects the peptide from rapid enzymatic degradation. The result is a prolonged circulation time that supports weekly administration.
The first regulatory approval, for type 2 diabetes, was granted in the United States in 2022. An additional approval for chronic weight management followed in 2023. Availability and approved indications vary by country and are set by each national regulator.
它属于合成修饰肽，同时激动 GIP 与 GLP-1 两种肠促胰素受体。这类分子通常被称为双重肠促胰素受体激动剂，与选择性 GLP-1 激动剂在靶点范围上不同。