dual agonist raises a handful of sensible questions. This page answers them in order, starting with the fundamentals and moving to applications.
This page was last updated on 2025-09-09 and is reviewed periodically as new material appears.
Tirzepatide is a synthetic peptide that acts as a dual agonist at the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. The molecule contains 39 amino acids and features a C20 fatty diacid moiety attached via a linker, which promotes albumin binding and extends its circulating half-life. Its sequence incorporates non-natural amino acids and modifications that reduce susceptibility to degradation by dipeptidyl peptidase-4. This dual receptor activity distinguishes it from selective GLP-1 receptor agonists.
The GIP receptor is expressed in pancreatic islets, adipose tissue, and the central nervous system, while GLP-1 receptors are found in pancreatic islets, the gastrointestinal tract, and the brain. Activation of both receptors can enhance glucose-dependent insulin secretion and reduce glucagon release. The relative contribution of each receptor to the overall pharmacological effect remains an area of ongoing investigation. Preclinical studies suggest that GIP receptor agonism may modulate appetite and energy balance, but the precise mechanisms in humans are not fully established.
质量控制环节关注外观、含量、纯度、有关物质、水分与微生物限度等项目。检测结果需要有对照品和系统适用性数据支持，单次测定不足以判定批次的稳定性。实验室之间方法转移时，色谱柱品牌与梯度差异常导致保留时间漂移，因此方法验证十分必要。
固体状态的 tirzepatide 通常以冻干粉形式保存，推荐在低温、避光、干燥条件下存放，常见区间为 2 至 8 摄氏度，长期保存可考虑更低温度并避免反复冻融。冻融循环会导致肽链聚集或析出，从而影响后续定量结果。容器密封性与湿度控制同样是稳定性研究中反复强调的因素。
| Property | Value | Notes |
|---|---|---|
| Molecular class | Synthetic peptide | Dual GIP/GLP-1 receptor agonist |
| Amino acid count | 39 | Contains non-natural residues |
| Modification | C20 fatty diacid | Attached via linker; promotes albumin binding |
| Half-life | Approximately 5 days | Supports once-weekly dosing |
| Primary route | Subcutaneous injection | Not for intravenous use |
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.
Tirzepatide activates both the glucose-dependent insulinotropic polypeptide receptor and the glucagon-like peptide-1 receptor, making it a dual agonist rather than a selective agent. Engagement of the GLP-1 receptor is linked to glucose-dependent insulin release, slower gastric emptying, and reduced appetite signalling. The relative contribution of the GIP arm remains an active research question; proposed roles include improved insulin sensitivity and altered adipose tissue handling. Receptor occupancy studies suggest the molecule interacts with both targets at circulating concentrations achieved during therapy.
Development began in the 2010s, when researchers modified a GIP-based scaffold to add GLP-1 activity and then attached the fatty diacid to lengthen its half-life. Clinical evaluation proceeded through large phase 3 programmes in type 2 diabetes and in obesity, and regulators in the United States cleared the compound for type 2 diabetes in 2022 and for chronic weight management in 2023. Several cardiovascular and metabolic outcome studies are still reporting, so the picture of long-term benefit and risk is incomplete. Approvals in other regions followed on different timelines.
Muslims are obliged to follow the decisions of Syariah Courts (i.e. Shariah courts) in matters concerning their religion. The Islamic judges are expected to follow the Shafi'i legal school of Islam, which is the main madhhab ('school of thought') of Malaysia. The jurisdiction of Syariah courts is limited to Muslims in matters such as marriage, inheritance, divorce, apostasy, religious conversion, custody, and limited Islamic criminal law. No other criminal or civil offences are under the jurisdiction of the Syariah courts, which have a similar hierarchy to the civil courts. The civil courts do not hear matters related to Islamic practices.
== Further reading == DuBois, Page (1991). Centaurs and Amazons: Women and the Pre-History of the Great Chain of Being. University of Michigan Press. ISBN 0-472-08153-5. Ewans, Michael (2007). Opera from the Greek: Studies in the Poetics of Appropriation. Ashgate Publishing, Ltd. ISBN 978-0-7546-6099-6. ISBN 978-0-7546-6099-6 Gregory, Justina (2005). A Companion to Greek Tragedy. Wiley-Blackwell. ISBN 1-4051-0770-7. Griffiths, Emma (2006). Medea. Taylor & Francis. ISBN 0-415-30070-3. ISBN 978-0-415-30070-4 Hall, Edith (1991). Inventing the Barbarian: Greek Self-definition through Tragedy. Oxford University Press. ISBN 0-19-814780-5. Haralu, L. (2017). Madwomen and Mad Women: An Analysis of the Use of Female Insanity and Anger in Narrative Fiction, From Vilification to Validation. ProQuest Dissertations Publishing. (Accession No. 10643100) Lootens, Barbara J. "Images of Women in Greek Drama." Feminist Teacher, vol. 2, no. 1, 1986, pp. 24–28. JSTOR, JSTOR 25680553. Accessed 27 Mar. 2023. Mastronarde, Donald (2002). Euripides: Medea. Cambridge University Press. ISBN 0-521-64386-4. McDermott, Emily (1989). Euripides' Medea: the Incarnation of Disorder. Penn State Press. ISBN 0-271-00647-1. ISBN 978-0-271-00647-5 McDonald, Marianne (1997). "Medea as Politician and Diva: Riding the Dragon into the Future". In Ckauss, James; Johnston, Sarah Iles (eds.). Medea: Essays on Medea in Myth, Literature, Philosophy, and Art. Princeton University Press. ISBN 0-691-04376-0. Mitchell-Boyask, Robin (2008). Euripides: Medea. Translated by Diane Arnson Svarlien. Hackett Publishing.
Eurogamer echoed criticism on the game's length; reviewer Tom Bramwell commented that "although I'm hard pressed to criticize what you get, the complete absence of everything we've learnt from the likes of Counter-Strike and everything since is frankly bizarre". Bramwell did, however, criticize the game's artificial intelligence and the occasional bug that caused a player to get stuck on a wall. PC Zone's Mark Hill was more lenient, praising the game's artificial intelligence as "intelligent as you could hope an AI enemy to be". In addition, Hill praised the game for showing more activity in the base, noting that "a whole world goes on around you, with people eating at a cantina and scientists doing their laundry. The complex is more alive than ever before". Hill also praised the focus "on a greater interaction with scientists as proper people rather than the two or three models that were cloned throughout the facility who kept repeating the same phrases", describing this as Blue Shift's "greatest achievement". PC Zone's review closed by commenting that "as a Dreamcast extra it works perfectly, but as a standalone PC title there's not nearly enough to it." In his negative review of the game, Jim Preston of NextGen recommended that players play the Half-Life mods They Hunger or Day of Defeat instead. The game sold around 800,000 units at retail, excluding digital sales on Steam.
=== Age of onset === The definition of the onset of puberty may depend on perspective (e.g., hormonal versus physical) and purpose (establishing population normal standards, clinical care of early or late pubescent individuals, etc.). A common definition for the onset of puberty is physical changes to a person's body. These physical changes are the first visible signs of neural, hormonal, and gonadal function changes. The age at which puberty begins varies between individuals; usually, puberty begins between 10 and 13 years of age. The age at which puberty begins is affected by both genetic factors and by environmental factors such as nutritional state and social circumstances. An example of social circumstances is the Vandenbergh effect; a juvenile female mouse who has significant interaction with adult male mice will enter puberty earlier than juvenile females who are not socially overexposed to adult males. The average age at which puberty begins may be affected by ethnicity as well. For example, the average age of menarche in various populations surveyed has ranged from 12 to 18 years. The earliest average onset of puberty is for African-American females and the latest average onset for high altitude subsistence populations in Asia. However, much of the higher age averages reflect nutritional limitations more than genetic differences and can change within a few generations with a substantial change in diet.
Sources: en.wikipedia.org
== Contraindications == Anyone who is unstable for surgery should not undergo flap surgery. As with most surgeries, people who are sicker may have more difficulties with wound healing. Comorbidities include diabetes, smoking, immunosuppression, and vascular disease.
Drugs are also used to inhibit enzymes needed for the survival of pathogens. For example, bacteria are surrounded by a thick cell wall made of a net-like polymer called peptidoglycan. Many antibiotics such as penicillin and vancomycin inhibit the enzymes that produce and then cross-link the strands of this polymer together. This causes the cell wall to lose strength and the bacteria to burst. In the figure, a molecule of penicillin (shown in a ball-and-stick form) is shown bound to its target, the transpeptidase from the bacteria Streptomyces R61 (the protein is shown as a ribbon diagram). Antibiotic drug design is facilitated when an enzyme that is essential to the pathogen's survival is absent or very different in humans. Humans do not make peptidoglycan, therefore antibiotics that inhibit this process are selectively toxic to bacteria. Selective toxicity is also produced in antibiotics by exploiting differences in the structure of the ribosomes in bacteria, or how they make fatty acids.
== Member of the National Assembly (2018-2023) == On 13 August 2018, Bilawal Zardari became a member of the National Assembly of Pakistan. In his inaugural speech, he asked Prime Minister Imran Khan to fulfill his promise of rooting out corruption, resolving the water crisis, providing 10 million jobs, and providing 5 million houses to the Pakistani people during his tenure. In the speech, Bilawal Zardari coined the term 'PM Select' for Khan. He added that Khan is not only the prime minister for the PTI, but he is also the Prime Minister of the Pakistani people, who Bilawal Zardari claimed that Khan referred to as "donkeys" and "living corpses." On 5 March 2019, Bilawal Zardari was elected—unopposed—as the chairperson of the National Assembly Standing Committee for Human Rights.
Tourism is a significant pillar for Jammu and Kashmir's economy, contributing substantially to employment and the gross domestic product. Estimates suggest that tourism accounts for around 7–15% of Jammu and Kashmir’s GDP, with approximately half of the population engaged directly or indirectly in tourism-related activities. The sector supports a wide range of economic activities, including hospitality, handicrafts, transport, and local services, and is vital for the socio-economic development of the territory. Some major tourist attractions are Srinagar, the Mughal Gardens, Gulmarg, Pahalgam, Patnitop, Bhaderwah and Jammu. Every year, thousands of Hindu pilgrims visit holy shrines of Vaishno Devi and Amarnath which has had significant impact on the economy. The Kashmir valley is one of the top tourist destinations in India. Gulmarg, one of the most popular ski resort destinations in India, is also home to the world's highest green golf course. The government has prioritised the development of tourism infrastructure and the promotion of both traditional and off-beat destinations, aiming to expand the sector and ensure sustainable growth. The tourism industry in Jammu and Kashmir has been profoundly affected by periods of insurgency, political instability, and violence. The onset of militancy in the late 1980s led to a dramatic decline in tourist arrivals, especially in the Kashmir Valley. For instance, tourist numbers in the valley fell from over 550,000 in 1989 to fewer than 10,000 in 1996, with both domestic and foreign tourism severely impacted.
=== Mortality === CRE resistance depends upon a number of factors such as the health of the patient, whether the patient has recently undergone a transplant, risk of co-infection, and use of multiple antibiotics. Carbapenem minimal inhibitory concentrations (MICs) results may be more predictive of clinical patient outcomes than the current categorical classification of the MICs being listed as susceptible, intermediate, or resistant. The study aimed to define an all-cause hospital mortality breakpoint for carbapenem MICs that were adjusted for risk factors. Another objective was to determine if a similar breakpoint existed for indirect outcomes, such as the time to death and length of stay after infection for survivors. Seventy-one patients were included, of which 52 patients survived and 19 patients died. Classification and regression tree analysis determined a split of organism MIC between 2 and 4 mg/liter and predicted differences in mortality (16.1% for 2 mg/liter versus 76.9% for 4 mg/liter). In logistic regression controlling for confounders, each imipenem MIC doubling dilution doubled the probability of death. This classification scheme correctly predicted 82.6% of cases. Patients were accordingly stratified to MICs of ≤2 mg/liter (58 patients) and ≥4 mg/liter (13 patients). Patients in the group with a MIC of ≥4 mg/liter tended to be more ill. Secondary outcomes were also similar between groups. Patients with organisms that had an MIC of ≥4 mg/liter had worse outcomes than those with isolates of an MIC of ≤2 mg/liter.
Sources: en.wikipedia.org
=== Large cap indices === Russell 1000 Index: The large-cap index of the top 1,000 stocks in the Russell 3000 Index. Russell Top 500 Index: Another large-cap index, consisting of the top 500 stocks in the Russell 1000 Index. Russell Top 200 Index: The mega-cap index of the very largest 200 stocks in the Russell 1000 Index. Russell Top 100 Index: Mega-cap index of the top 100 stocks in the Russell 1000 Index. Russell Top 50 Index: Measures the performance of the 50 largest mega-cap companies in the Russell 1000 Index. Russell Top 20 Index: Mega-cap index of the top 20 stocks in the Russell 1000 Index. Russell Top 10 Index: Mega-cap index of the top 10 stocks in the Russell 1000 Index.
== External links == HAND1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from the United States National Library of Medicine, which is in the public domain.
Izonsteride (developmental code name LY-320,236) is a selective inhibitor of the 5α-reductase, with dual effects on both the type I and type II isoforms of the enzyme. It was under development by Eli Lilly and Company and Fujisawa for the treatment of benign prostatic hyperplasia but was never marketed. Izonsteride may also be useful in the treatment of androgenic alopecia.
=== Tricuspid regurgitation === Patients with tricuspid regurgitation may experience symptoms of right-sided heart failure, such as ascites, hepatomegaly, edema and jugular venous distension. Signs of tricuspid regurgitation include pulsatile liver, prominent V waves and rapid y descents in jugular venous pressure. Auscultatory findings include inspiratory third heart sound at left lower sternal border (LLSB) and a blowing holosystolic murmur at LLSB, intensifying with inspiration, and decreasing with expiration and Valsalva maneuver. Patients may have a parasternal heave along LLSB. Atrial fibrillation is usually present in patients with tricuspid regurgitation
Sources: en.wikipedia.org
It activates both GIP and GLP-1 receptors. This dual action differentiates it from selective GLP-1 agonists.
It is given as a subcutaneous injection. Its long half-life supports weekly dosing.
No, it is synthetic. It contains non-natural amino acids and a fatty acid modification.
建议在低温、避光、干燥环境中密封保存，常见条件为 2 至 8 摄氏度，长期存放可置于更低温度。应避免反复冻融，并尽量减少容器开启次数。