The short version of incretin fits in a sentence. The long version — which is the one that helps — is below.
This page was last updated on 2026-02-04 and is reviewed periodically as new material appears.
Large randomised trials in adults with type 2 diabetes and in adults with obesity have reported reductions in body weight and improvements in several cardiovascular risk markers. One outcome trial found a lower incidence of major adverse cardiovascular events in participants with diabetes and established cardiovascular disease. Gastrointestinal effects such as nausea and vomiting are the most frequently reported adverse events and often diminish over time. Changes in lean body mass during weight loss are an area of ongoing investigation. Effects in adolescents and in pregnancy are less well characterised, and current labelling advises against use during pregnancy.
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released after nutrient intake. The molecule contains 31 amino acid residues and differs from the native sequence at several positions. A non-natural residue at position eight resists the enzyme that normally truncates the hormone, while a lysine-linked fatty diacid side chain promotes binding to serum albumin. These two modifications extend the circulating half-life from minutes to roughly one week. The peptide is produced by solid-phase synthesis followed by selective acylation, and its identity and purity are confirmed by spectrometric and chromatographic techniques.
Clinical studies of semaglutide generally measure glycated hemoglobin, fasting plasma glucose, body weight, and composite cardiovascular endpoints. The SUSTAIN program enrolled adults with type 2 diabetes, while the STEP program focused on obesity without diabetes. Administration follows a stepwise escalation schedule designed to limit gastrointestinal effects during the first weeks. Reported outcomes include mean percentage weight change, the proportion of participants reaching defined weight-loss thresholds, and rates of nausea, vomiting, and diarrhea. Long-term data on durability after treatment stops are still limited and remain a topic of ongoing research.
Semaglutide is a synthetic peptide analog of human glucagon-like peptide-1, developed by Novo Nordisk and first approved in 2017 for type 2 diabetes. It belongs to the incretin mimetic class, a group of agents that reproduce the glucose-dependent actions of endogenous GLP-1. The molecule was engineered to resist degradation by dipeptidyl peptidase-4 and to bind serum albumin, extending its half-life from minutes to roughly one week. Approval for chronic weight management followed in 2021, based on large cardiovascular and obesity outcome trials.
GLP-1 receptors are expressed on pancreatic beta cells, in the gut, and in several brain regions. Receptor activation raises cyclic AMP, enhances glucose-dependent insulin secretion, and suppresses glucagon release when blood glucose is high. Effects on gastric emptying and on hypothalamic appetite circuits reduce energy intake. Because insulin release remains glucose-dependent, the risk of hypoglycemia is low when the drug is used alone. The precise contribution of each pathway to body weight change in humans remains an area of active investigation.
| Property | Value | Notes |
|---|---|---|
| Molecular class | Acylated GLP-1 receptor agonist | 31-residue synthetic peptide |
| Molecular formula | C187H291N45O59 | established for the free peptide |
| Appearance | White to off-white powder | as supplied before formulation |
| Solubility | Freely soluble in water | aqueous buffers near neutral pH |
| Typical storage | 2 to 8 degrees Celsius, protected from light | powder and solution forms differ in shelf life |
Receptor activation follows the canonical Gs pathway: binding increases intracellular cyclic AMP, which promotes protein kinase A activity. In pancreatic beta cells this amplifies glucose-dependent insulin release, so secretion rises when blood glucose is high and changes little when it is low. The same signalling suppresses glucagon release from alpha cells and slows gastric emptying. Receptors in the hypothalamus and brainstem are thought to contribute to reduced appetite and lower energy intake. Which of these effects dominates clinical outcomes remains an area of active study.
Semaglutide is a synthetic peptide analogue of glucagon-like peptide-1, a gut hormone released by intestinal L cells after food intake. The natural hormone acts on pancreatic and central receptors but is degraded within minutes by dipeptidyl peptidase-4 and other peptidases. Semaglutide belongs to the class of long-acting GLP-1 receptor agonists, a group distinguished by structural changes that slow breakdown and extend circulation time. Its development followed earlier short-acting analogues and reflects a general strategy in peptide drug design: preserve receptor activity while blocking proteolytic clearance.
Three structural changes define the molecule. At position 8 an alpha-aminoisobutyric acid residue replaces alanine, which blocks dipeptidyl peptidase-4 cleavage. At position 34 arginine replaces lysine, and at position 26 a lysine carries a C18 fatty diacid attached through a short linker. The fatty chain binds serum albumin, and this albumin association reduces renal filtration and enzymatic attack. The unchanged backbone retains the receptor contacts that produce signalling. The free base has the formula C187H291N45O59 and a molecular weight near 4114 daltons.
Development began in the early 2010s with the goal of extending GLP-1 activity beyond the brief window achieved by native peptide infusion. The earliest approved formulation was a subcutaneous injection given once weekly. A later oral tablet pairs the peptide with an absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, usually shortened to SNAC. That carrier lowers local pH and helps the peptide cross gastric tissue. Both routes deliver the same active molecule.
Semaglutide is a synthetic peptide analog of human glucagon-like peptide-1, a gut hormone released after meals. Its backbone retains the GLP-1 sequence but incorporates two substitutions that slow enzymatic breakdown by dipeptidyl peptidase-4. A short polyethylene glycol linker and a C18 fatty diacid are attached to the peptide chain, allowing the molecule to bind serum albumin and remain in circulation far longer than the native hormone. The result is a circulating half-life measured in days rather than the minutes typical of endogenous GLP-1.
Receptor activation occurs at GLP-1 receptors distributed across pancreatic islets, the hypothalamus, and the gastrointestinal tract. Binding triggers G protein signaling that raises cyclic AMP and enhances glucose-dependent insulin release. Because the effect depends on prevailing glucose levels, insulin secretion does not rise when blood sugar is already low. Signaling in the brain and gut also influences appetite and gastric emptying, which is why the compound appears in both metabolic and weight-related research literature.
Serum protein binding dominates the pharmacokinetic profile. The attached chain associates strongly with albumin, shielding the peptide from enzymatic attack and slowing filtration by the kidney. This interaction extends the circulation half-life to roughly one week in humans, which supports weekly administration intervals. An oral version pairs the peptide with an absorption enhancer that transiently alters gastric epithelium, permitting limited uptake; bioavailability by that route is substantially lower than by injection.
Semaglutide belongs to the glucagon-like peptide-1 receptor agonist class, a group of synthetic peptides that imitate an incretin hormone released by intestinal L cells after food intake. Native GLP-1 circulates for only a few minutes because dipeptidyl peptidase-4 cleaves it rapidly. The hormone acts on pancreatic islets, the gastrointestinal tract, and several brain regions. Because the natural peptide is short-lived, development work concentrated on analogues that keep receptor activity while resisting enzymatic breakdown and renal clearance.
The semaglutide sequence is a 31-residue analogue of human GLP-1, altered at three positions relative to the parent hormone. Aminoisobutyric acid replaces alanine at position 8, arginine replaces lysine at position 34, and a lipophilic diacid is attached to lysine 26 through a short linker. These features are reported consistently in the structural literature. The position 8 substitution blocks recognition by dipeptidyl peptidase-4, while the attached chain drives strong, reversible association with a carrier protein in blood.
A gland is a cell or an organ in an animal's body that produces and secretes different substances that the organism needs, either into the bloodstream or into a body cavity or outer surface. A gland may also function to remove unwanted substances such as urine from the body. There are two types of gland, each with a different method of secretion. Endocrine glands are ductless and secrete their products, hormones, directly into interstitial spaces to be taken up into the bloodstream. Exocrine glands secrete their products through a duct into a body cavity or outer surface. Glands are mostly composed of epithelial tissue, and typically have a supporting framework of connective tissue, and a capsule.
==== Creatine ==== One of the most popular supplements is creatine. Although the body naturally produces creatine, it typically only produces enough to maintain around 60–80% of its full capacity. Creatine is most often found in red meats and seafood; however, a pound of uncooked beef and salmon only contains 1–2 grams of creatine. About 95% of creatine is stored in the skeletal muscle, while the remaining percentage is found in the brain and testes. Typical supplemental creatine doses are 3–5 grams per day. While taking creatine as a dietary supplement doesn't directly build muscle, it can lead to rapid energy production, increase improvement, enhance muscle recovery, prevent injuries, and provide neuroprotection. This is due to the fact that when creatine is paired with increased glycogen storage in the muscle, glycogen can quickly release glucose, providing an immense burst of energy. This burst of energy is helpful for professional bodybuilders, as anabolic steroids often cause fatigue and other health issues over time.
== Editorial board memberships == Current Signal Transduction Therapy (Bentham Sci. Publisher) Editor-in-Chief Current Opinion in Molecular Therapeutics (Thomson Reuters) Journal of Receptors and Signal Transduction, (Informa Healthcare) Endocrine (Springer) International Journal of Peptide Research and Therapeutics (Springer)
=== Displays === StoreDot was founded in 2012 by Doron Myersdorf, Simon Litsyn, and Gil Rosenman, initially developing displays and storage devices based on research by Ehud Gazit. A year later its CEO, Myersdorf, said their peptide-based display technology is ready to be "packed and sold" and its related intellectual property could be sold for 300 million dollars. The displays and storage devices were based on "peptide nanocrystals", and a prototype storage device was made in 2012 that is "three times faster than conventional memory." The company's CEO said the display technology is 20% more power-efficient and 90% less costly to manufacture than OLED, and the displays were ready in 2015 for full-scale manufacturing using existing factories and manufacturing processes, and were to be commercialized by 2016. By 2019 the display technology was spun off into its own company, MolecuLED. As of 2022, MolecuLED had no employees.
=== Aviptadil === In the wake of the COVID-19 pandemic, scientists at Relief conducted initial studies into the efficacy of RLF-100 in treating severe COVID-19 patients. In June 2020, the U.S. Food and Drug Administration granted fast-track designation to RLF-100 for treatment of respiratory distress in COVID-19. In September 2020, Relief partnered with US-Israeli firm NRX Pharmaceuticals (formerly NeuroRx Inc) for the co-development of the drug and the co-ordination of US trials. In April 2021, a reformulated version of aviptadil, known as Zyesami, was included in a National Institutes of Health (NIH) sponsored Phase 3 trial with the aim of testing aviptadil against remdesivir. In May 2021, NRX submitted a request for an Emergency Use Authorization (EUA) to the US FDA for aviptadil's use in patients in intensive care. On 7 October 2021 Relief Therapeutics filed a lawsuit against NRX Pharmaceuticals and its CEO Dr. Jonathan Javitt in the Supreme Court of the State of New York, citing multiple alleged breaches of the collaboration agreement signed by the two companies for the co-development of aviptadil. On 4 November 2021 the FDA declined EUA for the drug, but committed to working with NRX to further develop it. On 29 November 2021, NRX announced that data analysis from the NIH-sponsored Phase 3 trial showed a fourfold increase in survival at 60 days for patients administered with Zyesami (Aviptadil) vs those who received placebo.
Sources: en.wikipedia.org
Before the occupation, Jews in the area had become targeted during the Holocaust in the Sudetenland. Only a few weeks later, the Kristallnacht occurred. As elsewhere in Germany, many synagogues were set on fire and numerous leading Jews were sent to concentration camps. Jews and Czechs were not the only afflicted peoples since German socialists, communists and pacifists were widely persecuted as well. Some of the German socialists fled the Sudetenland via Prague and London to other countries. The Gleichschaltung would permanently alter the community in the Sudetenland. However, on 4 December 1938, there were elections in Reichsgau Sudetenland in which 97.32% of the adult population voted for the NSDAP. About a half million Sudeten Germans joined the Nazi Party, 17.34% of the total German population in the Sudetenland (the average NSDAP membership participation in Germany was merely 7.85% in 1944). That means the Sudetenland was one of the most pro-Nazi regions of Nazi Germany. Because of their knowledge of the Czech language, many Sudeten Germans were employed in the administration of the ethnic Czech Protectorate of Bohemia and Moravia as well as in Nazi organizations (Gestapo etc.). The most notable one was Karl Hermann Frank, the SS and police general and Secretary of State in the Protectorate. Nazi Germany occupied Sudetenland from 1938 to 1945. The annexation was supported by many Bohemian and Moravian Germans.
May 31: Decree regarding the admission of women to the role of Foreign Trade Advisor. June 14: The issuance of a passport no longer requires a husband's authorization for a married woman. September 30: Decree establishing a Higher Council for Child Protection. 1938
=== Clinical attachment level === The clinical attachment level (CAL) combines the measurements of probing pocket depth and any gingival recession to give an overall indication of where the periodontal tissues attach to the root surface. It is measured from a constant reference point, usually the CEJ, to the base of the periodontal pocket. Due to the more stable and reproducible property, this is considered the best measure of changes in residual periodontal support over time.
Vapour pressure is the pressure of a vapour in thermodynamic equilibrium with its condensed phases in a closed system. All liquids and solids have a tendency to evaporate into a gaseous form, and all gases have a tendency to condense back to their liquid or solid form. The atmospheric pressure boiling point of a liquid (also known as the normal boiling point) is the temperature at which the vapor pressure equals the ambient atmospheric pressure. With any incremental increase in that temperature, the vapor pressure becomes sufficient to overcome atmospheric pressure and lift the liquid to form vapour bubbles inside the bulk of the substance. Bubble formation deeper in the liquid requires a higher pressure, and therefore higher temperature, because the fluid pressure increases above the atmospheric pressure as the depth increases. The vapor pressure that a single component in a mixture contributes to the total pressure in the system is called partial vapor pressure.
== Description == The species grows to be about 50 mm, or about 2 inches. This slug has been treated as a model organism and used in studies into classical conditioning, memory consolidation and associative learning, the structure of neural circuits and neural physiology. It has also been used to investigate ultrastructure and anatomy, larval and reproductive ecology, behavioral ecology and pharmacology and toxicology including studies into Beta thymosins. Unfortunately these studies did not differentiate between the three species of Hermissenda.
Sources: en.wikipedia.org
is known as the kinematic viscosity. In this expression for Reynolds number, the characteristic length D is taken to be the hydraulic diameter of the pipe, which, for a cylindrical pipe flowing full, equals the inside diameter. In Figures 1 and 2 of friction factor versus Reynolds number, the regime Re < 2000 demonstrates laminar flow; the friction factor is well represented by the above equation. In effect, the friction loss in the laminar regime is more accurately characterized as being proportional to flow velocity, rather than proportional to the square of that velocity: one could regard the Darcy–Weisbach equation as not truly applicable in the laminar flow regime. In laminar flow, friction loss arises from the transfer of momentum from the fluid in the center of the flow to the pipe wall via the viscosity of the fluid; no vortices are present in the flow. Note that the friction loss is insensitive to the pipe roughness height ε: the flow velocity in the neighborhood of the pipe wall is zero.
== Further reading == The City of Albany, State of Oregon. Portland, OR: Lewis & Dryden Printing Co., 1891. "Mayors of Albany: Men Who Have Served Since the Earliest Municipal Organization," Morning Daily Herald [Albany], vol. 4, no. 33 (Jan. 6, 1889), pg. 3.
=== Protein === Due to alternative splicing, insulin-degrading enzyme has two isoforms. Isoform1 is ~118 kDa in size and composed of 1019 amino acids while the isoform 2 is ~54.2 kDa size and composed of 464 amino acids (missing 1-555 amino acids). The calculated theoretical pI of this protein isoform is 6.26. Structural studies of IDE by Shen et al. have provided insight into the functional mechanisms of the protease. Reminiscent of the previously determined structure of the bacterial protease pitrilysin, the IDE crystal structure reveals defined N and C terminal units that form a proteolytic chamber containing the zinc-binding active site. In addition, it appears that IDE can exist in two conformations: an open conformation, in which substrates can access the active site, and a closed state, in which the active site is contained within the chamber formed by the two concave domains. Targeted mutations that favor the open conformation result in a 40-fold increase in catalytic activity. Based upon this observation, it has been proposed that a possible therapeutic approach to Alzheimer's might involve shifting the conformational preference of IDE to the open state, and thus increasing Aβ degradation, preventing aggregation, and, ideally, preventing the neuronal loss that leads to disease symptoms.
There are quite a few physical characteristics that promote anti-microbial activity. However, most metal ions can create oxygen radicals, thus forming molecular oxygen which is highly toxic to bacteria.
There were also communist states in Africa, such as Ethiopia. In 1974, the military overthrew Emperor Haile Selassie and installed a military junta known as the Derg. The Derg quickly aligned itself with the Soviet Union on the basis of communism, implementing Marxist-Leninist ideals that were radical for their country. The brutal imposition of their radical ideas led to a debilitating civil war. In 1977, after a series of political purges and executions, Mengistu Haile Mariam became the leader of the Derg. He continued this course and brought Ethiopia closer to the USSR, which became Ethiopia's main trading partner, supplying it with everything from weapons and equipment to military advisers and specialists. Mengistu ultimately built a highly militarized state with the largest army in sub-Saharan Africa. The Soviet Union pushed Mengistu to create a "People's Democratic" system, as was the case in the Eastern Bloc countries, but Mengistu did so very reluctantly: Ethiopia became the "People's Democratic Republic of Ethiopia" only in 1987. And although the Derg was formally dissolved, roughly the same people remained in power as before. In the other four existing socialist and people's democratic states, namely China, Cuba, Laos, and Vietnam, the ruling parties hold Marxism–Leninism as their official ideology, although they give it different interpretations in terms of practical policy. Marxism–Leninism is also the ideology of anti-revisionist, Hoxhaist, Maoist, and neo-Stalinist communist parties worldwide.
Sources: en.wikipedia.org
Native GLP-1 is degraded within minutes by dipeptidyl peptidase-4 and neutral endopeptidases. Semaglutide carries a non-natural amino acid at position eight that blocks that cleavage, and a fatty diacid side chain that binds albumin. The result is a much longer duration of action than the native hormone.
The fatty diacid chain associates strongly with serum albumin, which keeps the peptide in circulation and shields it from rapid renal clearance. Bound peptide is released gradually, producing a sustained receptor signal. This mechanism also reduces the peak-to-trough variation seen with shorter-acting analogues.
The balance between peripheral receptor activation and signalling in the central nervous system is not fully resolved. The extent to which slowed gastric emptying accounts for reduced energy intake, compared with direct effects on appetite circuits, is debated. Long-term effects on lean mass and on tissues outside the gut and brain are still under study.
It is given either as a once-weekly subcutaneous injection or as an oral tablet taken once daily. The two forms use different absorption strategies, so they are not interchangeable on a milligram-for-milligram basis.