The short version of glucagon receptor fits in a sentence. The long version — which is the one that helps — is below.
This page was last updated on 2026-06-11 and is reviewed periodically as new material appears.
Clinical development has progressed through phase 2 trials in adults with obesity and type 2 diabetes, with phase 3 programs reported as ongoing. Reported outcomes include reductions in body weight and improvements in glycemic measures over defined treatment periods. Whether these effects translate into durable benefits after treatment ends remains an open question. Long-term safety data across broad populations are not yet complete, and regulatory decisions have not been announced.
Retatrutide is an investigational synthetic peptide engineered to activate three distinct hormone receptors within a single molecule. It targets the glucose-dependent insulinotropic polypeptide receptor, the glucagon-like peptide-1 receptor, and the glucagon receptor simultaneously. This triagonist design distinguishes it from earlier incretin-based compounds that act on one or two of these pathways. Structural modifications relative to native gut hormones extend its residence time in circulation. The molecule remains under clinical evaluation and is not approved for any indication.
Receptor activation produces downstream effects that differ by tissue. GLP-1 receptor signaling influences appetite regulation and insulin secretion in a glucose-dependent manner. GIP receptor activity contributes to metabolic handling of nutrients and may modulate adipose tissue. Glucagon receptor engagement raises energy expenditure and promotes hepatic lipid turnover, though the balance among these actions in humans is still being characterized. Preclinical models showed reductions in body weight and improved glycemic markers.
Published information places retatrutide in clinical development rather than on the market as an approved therapy. Early-stage and mid-stage trials have examined tolerability and changes in body weight, and larger studies continue to report results over time. Open questions include the durability of effects after treatment stops, the composition of weight lost, and cardiovascular outcomes over long periods. Statements about definitive benefit should therefore be treated as provisional. Regulatory status varies by jurisdiction and changes as applications are reviewed.
Retatrutide is an investigational synthetic peptide designed to activate three distinct receptor systems within a single molecule. Its pharmacological profile combines activity at the glucose-dependent insulinotropic polypeptide receptor, the glucagon-like peptide-1 receptor, and the glucagon receptor. This arrangement places it within a broader class of agents often described as multi-agonists, which contrast with compounds that engage one or two targets. Research interest centers on whether simultaneous signaling produces effects that single-receptor agonists cannot achieve alone. A single molecular entity also simplifies manufacturing and delivery logistics compared with combining separate agents.
Mechanistic proposals link each receptor to a different physiological role. Activation of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors is associated with reduced appetite, slower gastric emptying, and glucose-dependent insulin release. Glucagon receptor signaling, by contrast, is associated with increased energy expenditure and altered lipid handling, though it can also raise blood glucose. The design intent is to balance these contributions so that weight reduction is enhanced without unacceptable glycemic trade-offs. How well that balance holds across individuals is not fully resolved.
| Property | Value | Notes |
|---|---|---|
| Receptor targets | GIP, GLP-1, glucagon | One molecule activates all three pathways |
| Research identifier | LY3437943 | Code used in published trial reports |
| Development stage | Phase 3, reported as ongoing | Not approved by any regulatory agency |
| Route studied | Subcutaneous | Administration form used in clinical trials |
| Studied populations | Adults with obesity or type 2 diabetes | Enrollment criteria vary between trials |
Peptides in this class degrade mainly through hydrolysis, oxidation, and aggregation. The lipid modification improves plasma residence time but can also promote self-association in aqueous solution at higher concentrations. Oxidation of methionine and deamidation of asparagine residues are common chemical liabilities that accumulate during storage. Stability studies therefore track purity loss, aggregate formation, and changes in receptor-binding potency over time under defined temperature and humidity conditions.
Solid peptide is generally held as a lyophilised powder at low temperature to slow degradation, with desiccant to limit moisture uptake. Reconstituted solutions are less stable and are usually kept refrigerated and protected from light for short periods. Repeated freeze-thaw cycles are avoided because they encourage aggregation. Laboratory handling includes work in a fume hood or laminar flow cabinet to limit inhalation and contamination. Weighing and transfer steps are performed with antistatic tools to reduce static-driven loss of fine powder.
Characterising a peptide of this size relies on a combination of chromatographic and mass spectrometric techniques. Reversed-phase high-performance liquid chromatography separates the intact molecule from related impurities, while electrospray mass spectrometry confirms molecular mass and detects truncation or oxidation products. Peptide mapping after enzymatic digestion verifies the amino acid sequence and locates modified residues. Because the molecule carries a lipid chain, assays must also distinguish the correctly conjugated product from incompletely acylated species.
The three-receptor design places retatrutide in a distinct category relative to older incretin-based therapies. Single agonists target one receptor, and dual agonists target two. Adding a third target broadens the pharmacological footprint and introduces new trade-offs among efficacy, tolerability, and glucose control. How these trade-offs resolve in large trials is a central focus of current research.
Retatrutide is an investigational peptide studied for obesity and type 2 diabetes. It is a single synthetic molecule designed to activate three metabolic receptors simultaneously. The compound belongs to the incretin mimetic family, a group of peptides that imitate gut hormones involved in appetite and glucose control. Its research code is LY3437943, and it remains under clinical study rather than cleared for routine medical use.
The peptide backbone is chemically modified to resist rapid enzymatic breakdown in the body. A fatty acid side chain promotes binding to serum albumin, which slows renal clearance and supports an extended circulation time. These modifications allow less frequent administration than would be possible with an unmodified peptide. The precise contribution of glucagon receptor activation to the overall metabolic effect remains an area of active investigation, because glucagon raises glucose while also increasing energy expenditure.
Development has progressed through early- and mid-stage human studies in adults with obesity and with type 2 diabetes. Published phase 2 data reported reductions in body weight and improvements in glycemic markers over the treatment period. No regulatory agency has approved the compound for any indication, and it remains available only within controlled research settings. Whether benefits observed in trials translate into durable outcomes after treatment stops is not yet established.
Retatrutide is an investigational synthetic peptide that acts as an agonist at three distinct G protein-coupled receptors. It combines activity at the glucagon-like peptide-1 receptor, the glucose-dependent insulinotropic polypeptide receptor, and the glucagon receptor within a single molecule. This multi-receptor profile distinguishes it from earlier incretin-based compounds that engage one or two of these pathways. Researchers designed the molecule to test whether simultaneous activation produces greater metabolic effects than single or dual agonism alone.
Retatrutide is an investigational peptide developed by a pharmaceutical company as a multi-receptor agonist for treating obesity and type 2 diabetes. The compound emerged from research into gut-hormone analogues that act on several receptors simultaneously rather than on a single target. Early preclinical work examined how combined activity at three distinct receptors might produce greater metabolic effects than single-receptor compounds. Published phase 2 results have described substantial reductions in body weight among participants, although the compound remains unapproved in most jurisdictions as of the mid-2020s.
Pharmacologically, retatrutide acts as a triple agonist at the glucagon-like peptide-1 receptor, the glucose-dependent insulinotropic polypeptide receptor, and the glucagon receptor. Activation of the first two receptors is associated with improved insulin secretion and reduced appetite. The glucagon receptor component is thought to increase energy expenditure, a mechanism that distinguishes this molecule from dual-agonist compounds. Researchers continue to investigate how the three activities interact and whether the combined profile offers advantages that justify additional clinical testing.
Several questions about the compound remain unresolved. The durability of weight reduction after treatment stops, the frequency of gastrointestinal side effects, and the long-term cardiovascular profile are topics of ongoing study. Regulatory submissions and phase 3 trial outcomes have not been fully reported in the public literature. Because most available data come from controlled trials rather than general-population use, conclusions about effectiveness outside study settings are provisional. The distinction between established findings and open questions matters when interpreting early coverage of the drug.
== Notable people == Neal Asher, science fiction writer, born in Billericay Francis Thomas Bacon, engineer, born in Billericay Lee Barnard, footballer, went to school in Billericay Peter Bone, politician, born in Billericay Louise Boyce, model and writer, born in Billericay Nick Cater, author and journalist in Australia, born in Billericay Daniel Corbett, TV weather forecaster, lived in Billericay as a child Robert Denmark, middle- and long-distance athlete Justin Edinburgh, footballer, lived in Billericay, played for Tottenham Hotspur; played for and managed Billericay Town Lee Evans, comedian, went to school and lives in Billericay Mark Foster, swimmer, born in Billericay David Gandy, model, born and went to school in Billericay Wrey Gardiner, poet, editor and publisher, founded The Grey Walls Press in Billericay Teresa Gorman, politician, the constituency's high-profile former MP Lee Harrison, footballer, born in Billericay Chris Haywood, actor/producer, born in Billericay David Hopwood, banker, born in Billericay Ralph Izzard, journalist, born in Billericay Marshall Jefferson, music producer, lived in Billericay Perry McCarthy, racing driver Suzanne Maddock, actor, lives in Billericay Christopher Martin, Mayflower pilgrim, lived in Billericay Alison Moyet, pop singer, born in Billericay Richard Osman, TV producer and personality ("Pointless Friend" on BBC show Pointless), born in Billericay Kevin Painter, darts player, born in Billericay Paul Parker, was raised in Billericay and lived there when he became a professional footballer.
Under normal or unstressed conditions, NRF2 is kept in the cytoplasm by a cluster of proteins that degrade it quickly. Under oxidative stress, NRF2 is not degraded, but instead travels to the nucleus where it binds to a DNA promoter and initiates transcription of antioxidative genes and their proteins. NRF2 is kept in the cytoplasm by Kelch like-ECH-associated protein 1 (KEAP1) and Cullin 3, which degrade NRF2 by ubiquitination. Cullin 3 ubiquitinates NRF2, while Keap1 is a substrate adaptor protein that facilitates the reaction. Once NRF2 is ubiquitinated, it is transported to the proteasome, where it is degraded and its components recycled. Under normal conditions, NRF2 has a half-life of only 20 minutes. Oxidative stress or electrophilic stress disrupts critical cysteine residues in Keap1, disrupting the Keap1-Cul3 ubiquitination system. When NRF2 is not ubiquitinated, it builds up in the cytoplasm, and translocates into the nucleus. In the nucleus, it combines (forms a heterodimer) with one of small Maf proteins (MAFF, MAFG, MAFK) and binds to the antioxidant response element (ARE) in the upstream promoter region of many antioxidative genes, and initiates their transcription.
Modern birds communicate by visual and auditory signals, and the wide diversity of visual display structures among fossil dinosaur groups, such as horns, frills, crests, sails, and feathers, suggests that visual communication has always been important in dinosaur biology. Reconstruction of the plumage color of Anchiornis suggest the importance of color in visual communication in non-avian dinosaurs. A 2009 review indicated that non-avians used visual displays and possibly non-vocal sounds, such as hissing, jaw-grinding or -clapping, splashing, and wing-beating (possible in winged maniraptoran dinosaurs). Fossilized larynxes or voice boxes have been identified in two dinosaurs; the ankylosaurid Pinacosaurus and the neornithischian Pulaosaurus, the structures of which suggest that dinosaurs were capable of complex bird-like vocalizations. A 2016 study concludes that some dinosaurs may have produced closed-mouth vocalizations, such as cooing, hooting, and booming. These occur in both reptiles and birds and involve inflating the esophagus or tracheal pouches. Such vocalizations evolved independently in extant archosaurs numerous times, following increases in body size. The crests of some hadrosaurids and the nasal chambers of ankylosaurids may have been resonators. Birds have evolved a novel organ for vocalization, the syrinx, the earliest remains of which were found in a specimen of the duck-like Vegavis iaai dated 69 –66 million years ago. The syrinx may have supplemented and then replaced the larynx as a vocal organ during bird evolution.
Fourier-transform mass spectrometry (FTMS), or more precisely Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS), measures mass by detecting the image current produced by ions spiralling in the presence of a magnetic field. Instead of measuring the deflection of ions with a detector such as an electron multiplier, the ions are injected into a Penning trap (a static electric/magnetic ion trap) where they effectively form part of a circuit. Detectors at fixed positions in space measure the electrical signal of ions which pass near them over time, producing a periodic signal. Since the frequency of an ion's cycling is determined by its m/z ratio, this can be deconvoluted by Fourier transform on the signal. Ion cyclotron resonance (ICR) is an older mass analysis technique. It is similar to FTMS, in that the ions undergo cyclotron resonance. However, the ions are detected with a traditional detector. Ions trapped in a Penning trap are excited by an RF electric field until they impact the wall of the trap, where the detector is located. Ions of different mass are resolved according to impact time. FTMS is generally the most sensitive analyzer on the market, achieving resolution ~1 million. It achieves such high resolution, since each ion is "counted" multiple times by the spectrometer. From the perspective of the uncertainty principle of signal processing, an oscillating signal that is highly delocalized in time is also highly localized in frequency.
(2008); "Molecular Dynamics Simulation Methods including Quantum Effects"; In: Solvation Effects on Molecules and Biomolecules, Canuto, Sylvio (Eds.), ISBN 978-1-4020-8269-6, Springer, Heidelberg 2008, pp. 247–278. Rode, Bernd M.; Hofer, Thomas S.; Pribil, Andreas B.; Randolf, Bernhard R. (2010); "Simulations of Liquids and Solutions Based on Quantum Mechanical Forces"; In: Theoretical and Computational Inorganic Chemistry, van Eldik, Rudi; Harvey, Jeremy (Eds.), ISBN 978-0-12-380874-5, Elsevier, Amsterdam 2010, pp. 143–175. Hofer, Thomas S.; Pribil, Andreas B.; Randolf, Bernhard R.; Rode, Bernd M.; "Ab Initio Quantum Mechanical Charge Field Molecular Dynamics - A Nonparametrized First-Principle Approach to Liquids and Solutions"; In: Advances in Quantum Chemistry, Sabin, John R.; Brändas, Erkki (Eds.), ISBN 978-0-12-380898-1, Elsevier, Amsterdam 2010, 213–246. Jakschitz, Thomas; Fitz, Daniel; Rode, Bernd Michael (2012); "The origin of first peptides on earth: from amino acids to homochiral biomolecules"; In: Genesis - In The Beginning, Joseph Seckbach (Edp.), ISBN 978-94-007-2940-7, Springer, Dordrecht 2012, pp. 469–489. Lutz, Oliver M. D.; Messner, Christoph B.; Hofer, Thomas S.; Glätzle, Matthias; Huck, Christian W.; Bonn, Günther K.; Rode, Bernd M.; "Combined Ab Initio Computational and Infrared Spectroscopic Study of the cis- and trans-Bis(glycinato)copper(II) Complexes in Aqueous Environment"; J. Phys. Chem. Lett. 2013, 4, p. 1502-1506. DOI: 10.1021/jz400288c. Schwendinger, M. G.; Rode, Bend M.
Sources: en.wikipedia.org
=== Non-dairy milk offerings === In 1997, Starbucks first offered non-dairy milk at its U.S. stores with the introduction of soy milk. In 2007, Starbucks stopped using milk originating from rBGH-treated cows. The company also adopted a new dairy standard for all espresso-based drinks, switching from whole to 2% reduced fat milk. In 2015, Starbucks began serving coconut milk. In 2016, it began serving almond milk. In January 2020, oat milk became available nationally. The company also offers non-dairy creamers at retail in partnership with Nestlé SA. CEO Kevin Johnson said in a 2020 interview that, milk substitutes would be a big part of reducing carbon emissions. That effort has prompted vegans, environmentalists, people with lactose intolerance and others to urge the company to eliminate the upcharge for drinks made with dairy-free milk. PETA encouraged sit-ins at Starbucks locations and purchased Starbucks stock to draw attention to what they believe is an unfair charge. A Starbucks Canada spokesperson told ET Canada that customizations such as added flavours, non-dairy beverages or an additional shot of espresso, would incur an additional charge. In December 2020, Starbucks announced it would offer Oatly oat milk in all US stores starting in spring 2021. With the launch of their holiday menu in November 2024, Starbucks ended the upcharge for non-dairy milk additions to drinks.
Giving adrenaline (epinephrine) to prevent adverse reactions to antivenom before they occur might be reasonable in cases where they occur commonly. Antihistamines do not appear to provide any benefit in preventing adverse reactions.
=== North America === United States: US president Donald Trump declared his intent to take over the Gaza Strip, relocate its Palestinian inhabitants, and redevelop it into the "Riviera of the Middle East", although members of Trump's administration walked back on elements of the plan. The US's takeover of the Gaza Strip was supported by 15% of Americans, with 62% expressing opposition. US Senator Rand Paul wrote, "We have no business contemplating yet another occupation to doom our treasure and spill our soldiers' blood." Organizations such as Arab Americans for Trump and the Uncommitted National Movement criticized Trump's proposal.
== Insulin == Agonists: Chaetochromin (4548-G05) Insulin-like growth factor 1 Insulin-like growth factor 2 Insulin Insulin aspart Insulin degludec Insulin detemir Insulin glargine Insulin glulisine Insulin lispro Mecasermin Mecasermin rinfabate Antagonists: BMS-754807 S661 S961 Kinase inhibitors: Linsitinib Antibodies: Xentuzumab (against IGF-1 and IGF-2)
Sources: en.wikipedia.org
Thickening foliage provided the insurgents with concealment from South African patrols, and their tracks were obliterated by the rain. At the end of April or early May, PLAN cadres returned to Angola to escape renewed SADF search and destroy efforts and retrain for the following year. Another significant factor of the physical environment was South West Africa's limited road network. The main arteries for SADF bases on the border were two highways leading west to Ruacana and north to Oshikango, and a third which stretched from Grootfontein through Kavangoland to Rundu. Much of this vital road infrastructure was vulnerable to guerrilla sabotage: innumerable road culverts and bridges were blown up and rebuilt multiple times over the course of the war. After their destruction PLAN saboteurs sowed the surrounding area with land mines to catch the South African engineers sent to repair them. One of the most routine tasks for local sector troops was a morning patrol along their assigned stretch of highway to check for mines or overnight sabotage. Despite their efforts, it was nearly impossible to guard or patrol the almost limitless number of vulnerable points on the road network, and losses from mines mounted steadily; for instance, in 1977 the SADF suffered 16 deaths due to mined roads. Aside from road sabotage, the SADF was also forced to contend with regular ambushes of both military and civilian traffic throughout Ovamboland.
nonsense suppressor A factor which can inhibit the effects of a nonsense mutation (i.e. a premature stop codon) by any mechanism, usually either a mutated transfer RNA which can bind the mutated stop codon or some kind of ribosomal mutation.
The king cobra (Ophiophagus hannah) is the longest venomous snake in the world, and it can inject very high volumes of venom in a single bite. The venom LD50 is 1.80 mg/kg SC according to Broad et al. (1979). The mean value of subcutaneous LD50 of five wild-caught king cobras in Southeast Asia was determined to be 1.93 mg/kg. Between 350 and 500 mg (dry weight) of venom can be injected at once (Minton, 1974). In another study by Broad et al. (1979), the average venom quantity was 421 mg (dry weight of milked venom). The maximum venom yield is approximately 1000 mg (dry weight). The king cobra has a fearsome reputation. When annoyed, it spreads a narrow hood and growls loudly, but some scientists claim that their aggressiveness is grossly exaggerated. In most of the local encounters with live, wild king cobras, the snakes appear to be of rather placid disposition, and they usually end up being killed or subdued with hardly any histrionics. These support the view that wild king cobras generally have a mild temperament, and despite their frequent occurrence in disturbed and built-up areas, are adept at avoiding humans. Naturalist Michael Wilmer Forbes Tweedie felt that "this notion is based on the general tendency to dramatise all attributes of snakes with little regard for the truth about them. A moment's reflection shows that this must be so, for the species is not uncommon, even in populated areas, and consciously or unconsciously, people must encounter king cobras quite frequently.
Sources: en.wikipedia.org
It is a synthetic peptide triagonist that engages GIP, GLP-1, and glucagon receptors. Investigational compounds in this class are studied for metabolic conditions rather than for a single organ system.
No regulatory agency has approved it for any indication. It remains an investigational product studied within controlled clinical trial programs.
A dual agonist engages two receptor targets, typically GIP and GLP-1. A triagonist adds glucagon receptor activity, which is intended to influence energy expenditure alongside appetite and glucose handling.
It is described as a single molecule that acts at three receptors: the glucose-dependent insulinotropic polypeptide receptor, the glucagon-like peptide-1 receptor, and the glucagon receptor. This triple activity distinguishes it from agents that target one or two of these pathways.