GLP-1 receptor agonist

  1. Home
  2. Wiki

Glucagon-like peptide-1 (GLP-1) receptor agonists, also known as GLP-1 agonists, GLP-1RAs, GLP-1 analogs, or incretin mimetics, are a class of medications that activate the GLP-1 receptor, causing reduced blood sugar, reduced appetite, and reduced energy intake. Originally manufactured for treatment of type 2 diabetes, some of these medications have been approved for weight loss in obesity. GLP-1 agonists mimic the actions of the endogenous incretin hormone GLP-1, which is released in the small intestine and can inhibit glucagon release and increasing release of insulin secretion.[1]

GLP-1 receptor agonists are used to treat type 2 diabetes and obesity, and are in development for treatment of non-alcoholic fatty liver disease, polycystic ovary syndrome, and diseases of the reward system, such as addictions.

Pharmacology

[edit]

Mechanism of action

[edit]

GLP-1 agonists work by activating the GLP-1 receptor, which is found all around the body. Some sites are on beta cells in the pancreas and on neurons in the brain. GLP-1 receptor activation slows gastric emptying, inhibits the release of glucagon, and stimulates insulin production, thereby improving glucose homeostasis in people with type 2 diabetes. GLP-1 receptor activation also stimulates satiety, thus reducing food intake, promoting the development of a negative energy balance, and decreasing body weight over time, making GLP-1 agonists a treatment option for obesity.[2] Another class of anti-diabetes drugs, DPP-4 inhibitors, work by reducing the breakdown of endogenous GLP-1, and are generally considered less potent than GLP-1 agonists.[3] Some of the metabolic effects of GLP-1 agonists in rodents are mediated via increased synthesis of fibroblast growth factor 21. Pharmaceutical companies have developed dual GLP-1/FGF21 receptor agonists.[4]

Pharmacokinetics

[edit]

The naturally occurring native GLP-1 hormone is considered a peptide hormone. It has a half-life of only about two minutes, because the dipeptidyl peptidase-4 (DPP-4) enzyme rapidly breaks it down.[5] As a result, different GLP-1 agonist drugs are modified in various ways to extend the half-life, resulting in drugs that can be dosed daily, weekly, or less often.[5] Many commonly used synthetic GLP-1 agonists are delivered weekly by subcutaneous injection, which is a barrier to their use and reason for discontinuation.[6] Most GLP-1 medications are approved by the FDA and sold as drug-device combination products, which include auto-injecting pens.[7] Self-injected drugs are especially difficult for people with vision or motor difficulties, which commonly accompany type 2 diabetes.[5] Attempts to develop an orally bioavailable GLP-1 agonist, either a modified peptide, as in the case of oral semaglutide,[6] or a small molecule drug, have produced additional drug candidates.[8] Other companies have tested inhaled or transdermal administration.[5]

Uses

[edit]

Type 2 diabetes

[edit]

GLP-1 agonists were initially developed to treat type 2 diabetes.[9] The 2025 American Diabetes Association (ADA) standards of medical care in diabetes include GLP-1 agonists or SGLT2 inhibitors as a first-line pharmacological therapy for type 2 diabetes in people who have or are at high risk for atherosclerotic cardiovascular disease or heart failure.[10] ADA also recommends GLP-1 agonists for people with both type 2 diabetes and kidney disease. Both GLP-1 agonists and SGLT2 inhibitors can be combined with metformin, which has shown an enhanced lowering of A1C.[10] GLP-1 receptor agonists should not be used in combination with DPP-4 enzyme inhibitors due to lack of evidence supporting the enhancement of the GLP-1.[11] One advantage of GLP-1 agonists over older insulin secretagogues such as sulfonylureas or meglitinides is that they have a lower risk of causing hypoglycemia, while improving weight and cardiovascular and kidney health.[10] ADA also recommends use of GLP-1 agonists instead of starting insulin therapy in people with type 2 diabetes who need additional glucose control, except when catabolism, hyperglycemia, or autoimmune diabetes is suspected.[12]

A 2021 meta-analysis found a 12% reduction in all-cause mortality when GLP-1 analogs are used in the treatment of type 2 diabetes, as well as significant improvements in cardiovascular and renal outcomes relative to nonusers.[13] A 2023 meta-analysis including 13 cardiovascular outcome trials found that SGLT2 inhibitors reduce the risk for three-point major adverse cardiovascular events, especially in subjects with an estimated glomerular filtration rate (eGFR) below 60 mL/min, whereas GLP-1 receptor agonists were more beneficial in people with higher eGFRs.[14] Likewise, the relative risk reduction of SGLT-2 inhibitor treatment was larger in populations with a higher proportion of albuminuria, but this relationship was not observed for GLP-1 receptor agonists. This suggests differential use of the two substance classes in people with preserved and reduced renal function or with and without diabetic nephropathy, respectively.[14] GLP-1 agonists and SGLT2 inhibitors work to reduce HbA1c by different mechanisms and can be combined for enhanced effects. It is also possible that they provide additive cardioprotective effects.[15]

The FDA has not approved GLP-1 agonists for type 1 diabetes, but they can be used off-label in addition to insulin to help people with type 1 diabetes improve their body weight and glucose control.[12]

Obesity

[edit]

GLP-1 agonists are recommended as an add-on therapy to lifestyle intervention (calorie restriction and exercise) in people with a BMI 30 kg/m or with a BMI 27 kg/m with at least one weight-related comorbidity, which can include high blood pressure or high cholesterol.[16] Some GLP-1 agonists are more effective than other weight-loss drugs, but bariatric surgery is still considered the most effective and sustainable way to lose weight.[17] GLP-1 agonists' weight-reducing effects come from a combination of peripheral effects and activity in the central nervous system.[18] In the brain, GLP-1 agonists reduce weight by crossing the blood–brain barrier, via passive diffusion or receptor mediated transcytosis, and directly activating the satiety hormones in the hypothalamus.[19]

In recent years, GLP-1 agonists have become more popular for both their on- and off-label uses. Three GLP-1 auto-injector medications are approved specifically for weight management: Wegovy (semaglutide),[20] Zepbound (tirzepatide),[21] and Saxenda (liraglutide).[22] Each of their clinical trials found a significant increase in the reduction of overall BMI in participants, ranging from 16% to 20%.

Studies have found that on average people regain more than half (50–70%) of the lost weight within a year after discontinuing any of these medications.[23]

Metabolic dysfunction–associated steatotic liver disease

[edit]

In a 2023 systematic review, researchers found that GLP-1 agonists are as effective a treatment for metabolic dysfunction–associated steatotic liver disease (MASLD) as the medications in current use, pioglitazone and Vitamin E. It was also noted that there was a reduction in steatosis, ballooning necrosis, lobular inflammation, and fibrosis.[24] The review also found promising signs for the continuation of GLP-1 medication therapy to treat MASLD.

As of August 2025, Weogvy (semaglutide) has been approved by the FDA to treat MASH (metabolic dysfunction-associated steatohepatitis) with stage 2 or stage 3 fibrosis of the liver. The mechanism of action for this treatment is still under investigation, but part 1 of its stage 3 clinical trials saw a 60% reduction in liver inflammation.[25] Clinical trials are ongoing.

Polycystic ovary syndrome

[edit]

GLP-1 agonists are recommended as a treatment for polycystic ovary syndrome, alone or in combination with metformin. The combination therapy has shown greater efficacy in improving body weight, insulin sensitivity, hyperandrogenism, and menstrual cycle irregularities.[26] This usage is off-label.[27]

Adverse effects

[edit]

GLP-1 agonists' most common adverse effects are gastrointestinal.[16] These limit the maximum tolerated dose and require gradual dose escalation.[8] Nausea, vomiting, diarrhea, and constipation are all commonly reported.[16] Nausea is directly related to the GLP-1 agonist's serum concentration and is reported in up to three-quarters of people using short-acting GLP-1 agonists but fewer of those using long-acting agonists. Reactions at the injection site are also common, especially with shorter-acting drugs.[5]

Human trials and meta-analyses have found no reliable association between the drugs and pancreatitis or pancreatic cancer, but some case reports of pancreatitis have emerged in postmarketing reports, and the American Association of Clinical Endocrinologists recommends caution in people with a history of pancreatitis. Discontinuation is recommended if acute pancreatitis occurs.

GLP-1 agonists appear to increase the risk of non-arteritic anterior ischemic optic neuropathy, but further research is needed to establish whether the association is causal.[28]

Some people develop anti-drug antibodies, which are more common with exenatide (the antibodies were detectable in a third or more of people) than other GLP-1 agonists and can decrease the drug's efficacy.[5] GLP-1 agonists increase the risk of gallstones when used to induce rapid weight loss.[16]

GLP-1 agonists may increase the risk of aspiration during anesthesia due to delayed gastric emptying, according to case reports. In 2023, the American Society of Anesthesiologists suggested holding the GLP-1 agonists on the day of the procedure/surgery or a week earlier.[29]

A 2024 study suggests that GLP-1 weight-loss medications do not increase the risk of suicide or suicidal thoughts in children and adolescents, contrary to some previous concerns.[30] The study included over 54,000 U.S. adolescents and found a 33% reduction in the risk of suicidal thoughts and attempts among those using the drugs compared to those who did not.[31] Additionally, while adolescents taking GLP-1 drugs experienced more gastrointestinal symptoms, they had a lower risk of acute pancreatitis compared to the control group.[32] A similar study in adults found similar results for semaglutide.[33]

A 2025 study suggested that GLP-1 agonists increased risks of hypotension (low blood pressure), syncope (fainting), joint diseases, nephrolithiasis (kidney stones), interstitial nephritis, and acute pancreatitis.[34]

Thyroid cancer

[edit]

The FDA requires a boxed warning in the package inserts of GLP-1 agonists due to the risk of thyroid C-cell tumors, including medullary thyroid cancer (MTC). The warning says that GLP-1 agonists are contraindicated in people with a family or personal history of MTC or multiple endocrine neoplasia type 2.[12] In mice, long-term use of GLP-1 agonists stimulates calcitonin secretion, leading to C-cell hypertrophy and increased risk of thyroid cancer, but no increased secretion of calcitonin has been observed in humans.[5] A retrospective national cohort study in France found an increased risk of thyroid cancer (all and medullary) after 1-3 years of treatment with GLP-1 agonists for diabetes,[35] but other large retrospective studies have not found a similar association,[36] including with long-term use of GLP-1 agonists and over 10 years of followup.[37]

Society and culture

[edit]

Cost

[edit]

GLP-1 agonists are more expensive than other treatments for type 2 diabetes. A study compared the cost-effectiveness of GLP-1 agonists to long-acting insulin in a Taiwanese population with type 2 diabetes. In people with CVD, GLP-1 agonists were estimated to save money due to fewer cardiovascular incidents. In people without CVD, the cost per QALY was $9,093.[38] In the United States, cost is the highest barrier to GLP-1 agonist usage and was reported as the reason for discontinuation in 48.6% of people who stopped using the drugs.[39] According to another study, GLP-1 agonists are not cost-effective for pediatric obesity in the U.S.[40]

[edit]

Discontinued:

  • exenatide (brand names Byetta and Bydureon, manufactured by AstraZeneca), approved 2005/2012,[45] discontinued in 2024
  • albiglutide (Tanzeum, manufactured by GSK), approved in 2014,[46] discontinued in 2017
  • lixisenatide (Lyxumia in Europe, Adlyxin in the United States, manufactured by Sanofi), approved in 2016,[47] discontinued in 2023

Combination and multiple target drugs

[edit]
See also: GLP1 poly-agonist peptides

Some GLP-1 agonists, such as tirzepatide, are also agonists of the GIP receptor, glucagon receptor, and/or amylin receptor. These additional targets are hoped to increase the amount of weight loss the drugs cause.[48][8]

Off-label and gray-market usage

[edit]

Influencers and celebrities popularized GLP-1 agonists in the early 2020s, causing many people to seek them for cosmetic or health-based weight loss.[49] Gray market sellers offer unauthorized products they claim are GLP-1 agonists. This is illegal in the U.S., but some buyers turn to unauthorized retailers after being denied insurance coverage if they cannot afford the name-brand drug.[50][51][52][53][54] Buyers face risks due to counterfeit or substandard drugs.[55]

In the U.S., the FDA declared shortages of injectable versions of semaglutide, tirzepatide, dulaglutide, liraglutide, and exenatide in 2022. The tirzepatide shortage ended in 2024.[56] During a declared shortage, compounding pharmacies may sell custom-made versions of the drug if they obtain the active pharmaceutical ingredient from an FDA-approved facility.[57] An estimated 95% of online pharmacies were operating illegally in 2024.[58]

History

[edit]

During the 1980s, Jean-Pierre Raufman worked as a postdoctoral researcher at the National Institutes of Health for John Pisano, a biochemist who specialized in collecting venoms from various animals and looking for novel substances that could affect human physiology.[59] In the course of this work, Raufman focused on investigating the Gila monster because he was curious about how it only eats once or twice per year.[60] He found that Gila monster venom had biologically active molecules that provoked inflammation of the pancreas in test animals.[60][61]

In 1992, after learning of Raufman's findings, John Eng of the Veterans Administration Medical Center in New York City used the radioimmunoassay technique he had learned from Nobel laureate Rosalyn Sussman Yalow to isolate a novel substance from Gila monster venom.[60][59][61] The new substance, which Eng called exendin-4, was similar to GLP-1 in that it reduced blood glucose in diabetic mice, but exendin-4 had a much longer half-life than GLP-1, whose extremely short half-life had defeated earlier attempts to turn it into a drug.[59][61]

Eng's employer, the U.S. Department of Veterans Affairs, had no interest in obtaining a drug patent on exendin-4, so Eng filed the patent application himself in 1993.[59] He then spent three years searching for a pharmaceutical industry partner interested in commercializing exendin-4.[60][59][61] In 1996, Amylin Pharmaceuticals licensed Eng's patent and created a synthetic version of exendin-4 called exenatide.[60][59][61] In 2002, Eli Lilly entered into an alliance with Amylin to further develop exenatide and secure official approval to market the drug.[62] Exenatide's 2005 approval by the U.S. Food and Drug Administration[63] was a landmark event that proved that targeting the GLP-1 receptor was a viable strategy and inspired other pharmaceutical companies to focus their research and development on that receptor.[59][61]

In 2011, Lilly and Amylin dissolved their partnership, with Amylin keeping the rights to exenatide.[64] Meanwhile, Lilly had been awakened to the possibilities of this class of drugs and continued to develop newer drugs of the same class.

The 2024 American Diabetes Association conference included presentations on at least 27 GLP-1 receptor agonists then in development.[65] By July 2024, Novo Nordisk's semaglutide and Eli Lilly's tirzepatide were ranked among the most popular and lucrative drugs in the world.[66] Novo Nordisk's successful rollout of semaglutide turned it into the most valuable company in Europe in 2024.[67][68] Its market capitalization of $570 billion was larger than the entire economy of its home country of Denmark, its $2.3 billion income tax bill for 2023 made it the country's largest taxpayer, and its rapid growth drove nearly all of the expansion of Denmark's economy.[67][68] By October 2024, tirzepatide had turned Eli Lilly into the world's most valuable drug company.[69]

Research

[edit]

A retrospective cohort study published in 2025 evaluated GLP-1 agonists' benefits and risks compared to other anti-diabetic medications. The study suggested that GLP-1 agonists reduced risks of substance use and psychotic disorders, seizures, neurocognitive disorders (including Alzheimer's disease and other dementias), coagulation disorders, cardiometabolic disorders, infectious diseases, and several respiratory conditions relative to nonusers.[34]

It is being researched whether GLP1 poly-agonist peptides, dual and triple receptor agonists such as tirzepatide (GLP-1 + GIP) and retatrutide (GLP-1 + GIP + glucagon), and combinations like cagrilintide/semaglutide, which combines semaglutide with a dual amylin and calcitonin receptor agonist, offer an advantage over single-receptor agonists.[5][70][71]

Cardiovascular effects

[edit]

GLP-1 agonists have demonstrated cardioprotective effects when used to treat obesity, beyond their primary roles in glycemic control and weight reduction.[72]

GLP-1 agonists may be beneficial in heart failure with preserved ejection fraction.[73]

Cancer

[edit]

In a retrospective study, GLP-1 exposure was associated with lower risks of specific types of obesity-associated cancers compared with insulin or metformin in people with type 2 diabetes. Compared to people using insulin, people taking GLP-1 agonists showed significant risk reduction in esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancer, as well as meningioma and multiple myeloma. Kidney cancers showed an increased risk with GLP-1 treatment relative to those treated with metformin.[74]

Depression

[edit]

GLP-1 agonists have shown antidepressant and neuroprotective effects. They can also be used to treat the metabolic consequences of second-generation antipsychotics, such as obesity.[75][76]

Reward system disorders

[edit]

GLP-1 agonists are under development for substance use disorder, a condition with few pharmacological treatment options. They reduce the self-administered intake of drugs and alcohol in non-human animals, though this effect has not been proven in humans. The mechanism of their addiction-reducing effect is unknown.[77] GLP-1 agonists are also under investigation for the treatment of binge eating disorder, the most common eating disorder.[78][79]

References

[edit]
  1. ^ Ross, Stuart A.; Ekoé, Jean-Marie (July 2010). "Incretin agents in type 2 diabetes". Canadian Family Physician Medecin de Famille Canadien. 56 (7): 639–648. PMC 2922799. PMID 20631270.
  2. ^ Drucker, Daniel J. (2022). "GLP-1 physiology informs the pharmacotherapy of obesity". Molecular Metabolism (Review). 57 101351. doi:10.1016/j.molmet.2021.101351. PMC 8859548. PMID 34626851.
  3. ^ Brunton, Stephen (2014). "GLP-1 Receptor Agonists vs. DPP-4 Inhibitors for Type 2 Diabetes". International Journal of Clinical Practice (Review). 68 (5). Wiley: 557–567. doi:10.1111/ijcp.12361. PMC 4238422. PMID 24499291.
  4. ^ Shao, Weijuan; Jin, Tianru (2022). "Hepatic hormone FGF21 and its analogues in clinical trials". Chronic Diseases and Translational Medicine (Review). 8 (1): 19–25. doi:10.1016/j.cdtm.2021.08.005. PMC 9126297. PMID 35620160.
  5. ^ a b c d e f g h Yu, Minzhi; Benjamin, Mason M.; Srinivasan, Santhanakrishnan; et al. (2018). "Battle of GLP-1 delivery technologies". Advanced Drug Delivery Reviews. 130: 113–130. doi:10.1016/j.addr.2018.07.009. PMC 6843995. PMID 30009885.
  6. ^ a b Antza, Christina; Nirantharakumar, Krishnarajah; Doundoulakis, Ioannis; et al. (2019). "The development of an oral GLP-1 receptor agonist for the management of type 2 diabetes: evidence to date". Drug Design, Development and Therapy. 13: 2985–2996. doi:10.2147/DDDT.S166765. PMC 6709822. PMID 31686781.
  7. ^ Alhiary, Rasha; Gabriele, Sarah; Kesselheim, Aaron S.; Tu, S. Sean; Feldman, William B. (5 March 2024). "Delivery Device Patents on GLP-1 Receptor Agonists". JAMA. 331 (9): 794–796. doi:10.1001/jama.2024.0919. PMC 10845039. PMID 38315473.
  8. ^ a b c Knerr, Patrick J.; Mowery, Stephanie A.; Finan, Brian; et al. (2020). "Selection and progression of unimolecular agonists at the GIP, GLP-1, and glucagon receptors as drug candidates". Peptides. 125 170225. doi:10.1016/j.peptides.2019.170225. PMID 31786282.
  9. ^ Brown, Emily; Heerspink, Hiddo J L; Cuthbertson, Daniel J; Wilding, John P H (July 2021). "SGLT2 inhibitors and GLP-1 receptor agonists: established and emerging indications". The Lancet. 398 (10296): 262–276. doi:10.1016/S0140-6736(21)00536-5. PMID 34216571.
  10. ^ a b c ElSayed, Nuha A.; McCoy, Rozalina G.; Aleppo, Grazia; Bajaj, Mandeep; Balapattabi, Kirthikaa (2025). "9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025". Diabetes Care. 48 (Supplement_1): S181 – S206. doi:10.2337/dc25-S009. PMC 11635045. PMID 39651989.
  11. ^ asploro (2025-01-14). "The Latest topics of Standards of Care in Diabetes 2025: Focusing on GLP-1RA". Retrieved 2025-11-17.
  12. ^ a b c Nachawi, Noura; Rao, Pratibha PR; Makin, Vinni (2022). "The role of GLP-1 receptor agonists in managing type 2 diabetes". Cleveland Clinic Journal of Medicine (Review). 89 (8): 457–464. doi:10.3949/ccjm.89a.21110. PMID 35914933.
  13. ^ Sattar, Naveed; Lee, Matthew M Y; Kristensen, Søren L; Branch, Kelley R H; Del Prato, Stefano; Khurmi, Nardev S; Lam, Carolyn S P; Lopes, Renato D; McMurray, John J V; Pratley, Richard E; Rosenstock, Julio; Gerstein, Hertzel C (October 2021). "Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials". The Lancet Diabetes & Endocrinology. 9 (10): 653–662. doi:10.1016/S2213-8587(21)00203-5. PMID 34425083.
  14. ^ a b Sohn, Minji; Dietrich, Johannes W.; Nauck, Michael A.; Lim, Soo (2023). "Characteristics predicting the efficacy of SGLT-2 inhibitors versus GLP-1 receptor agonists on major adverse cardiovascular events in type 2 diabetes mellitus: a meta-analysis study". Cardiovascular Diabetology (Research). 22 (1). BioMed Central: 153. doi:10.1186/s12933-023-01877-6. PMC 10303335. PMID 37381019.
  15. ^ DeFronzo, Ralph A. (2017). "Combination therapy with GLP-1 receptor agonist and SGLT2 inhibitor". Diabetes, Obesity & Metabolism (Review). 19 (10): 1353–1362. doi:10.1111/dom.12982. PMC 5643008. PMID 28432726.
  16. ^ a b c d Wharton, Sean; Davies, Melanie; Dicker, Dror; et al. (2022). "Managing the gastrointestinal side effects of GLP-1 receptor agonists in obesity: recommendations for clinical practice". Postgraduate Medicine (Commentary). 134 (1): 14–19. doi:10.1080/00325481.2021.2002616. PMID 34775881.
  17. ^ Müller, Timo D.; Blüher, Matthias; Tschöp, Matthias H.; DiMarchi, Richard D. (March 2022). "Anti-obesity drug discovery: advances and challenges". Nature Reviews Drug Discovery (Review). 21 (3): 201–223. doi:10.1038/s41573-021-00337-8. PMC 8609996. PMID 34815532.
  18. ^ Grill, Harvey J (2020). "A Role for GLP-1 in Treating Hyperphagia and Obesity". Endocrinology (Article). 161 (8) bqaa093. Oxford Academic. doi:10.1210/endocr/bqaa093. PMC 7899438. PMID 32516384.
  19. ^ Dong, Meiyuan; Wen, Song; Zhou, Ligang (2022). "The Relationship Between the Blood-Brain-Barrier and the Central Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter-2 Inhibitors". Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 15: 2583–2597. doi:10.2147/DMSO.S375559. ISSN 1178-7007. PMC 9417299. PMID 36035518.
  20. ^ "Weight Loss Medication | Wegovy® (semaglutide) Injection 2.4 mg". www.wegovy.com. Retrieved 2025-11-17.
  21. ^ "What is Zepbound | Obesity & Excess Weight | Zepbound® (tirzepatide)". zepbound.lilly.com. Archived from the original on 2025-09-02. Retrieved 2025-11-17.
  22. ^ "Prescription Weight-Loss Medicine | Saxenda® (liraglutide) injection 3mg". www.saxenda.com. Retrieved 2025-11-17.
  23. ^ Quarenghi, Massimo; Capelli, Silvia; Galligani, Giulia; Giana, Arianna; Preatoni, Giorgia; Turri Quarenghi, Rosamaria (28 May 2025). "Weight Regain After Liraglutide, Semaglutide or Tirzepatide Interruption: A Narrative Review of Randomized Studies". Journal of Clinical Medicine. 14 (11): 3791. doi:10.3390/jcm14113791. PMC 12155999. PMID 40507553.
  24. ^ Gu, Yunpeng; Sun, Lei; He, Yining; Yang, Luping; Deng, Chaohua; Zhou, Run; Kong, Tingting; Zhang, Wei; Chen, Yutong; Li, Jie; Shi, Junping (4 March 2023). "Comparative efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists, pioglitazone and vitamin E for liver histology among patients with nonalcoholic fatty liver disease: systematic review and pilot network meta-analysis of randomized controlled trials". Expert Review of Gastroenterology & Hepatology. 17 (3): 273–282. doi:10.1080/17474124.2023.2172397. PMID 36689199.
  25. ^ Research, Center for Drug Evaluation and (2025-08-15). "FDA Approves Treatment for Serious Liver Disease Known as 'MASH'". FDA.
  26. ^ Siamashvili, Maka; Davis, Stephen N. (2021). "Update on the effects of GLP-1 receptor agonists for the treatment of polycystic ovary syndrome". Expert Review of Clinical Pharmacology (Review). 14 (9). Taylor & Francis: 1081–1089. doi:10.1080/17512433.2021.1933433. PMID 34015974.
  27. ^ Hopkins, Caroline (24 June 2023). "Researchers keep discovering new uses for Ozempic. Proving it works isn't easy". Health News. NBC News. Retrieved 26 December 2023.
  28. ^ Hsu, Alan Y.; Kuo, Hou-Ting; Wang, Yu-Hsun; Lin, Chun-Ju; Shao, Yi-Ching; Chiang, Chun-Chi; Hsia, Ning-Yi; Lai, Chun-Ting; Tseng, Hsin; Wu, Bing-Qi; Chen, Huan-Sheng; Tsai, Yi-Yu; Hsu, Min-Yen; Wei, James Cheng-Chung (1 May 2025). "Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy Risk Among Patients With Diabetes". JAMA Ophthalmology. 143 (5): 400–407. doi:10.1001/jamaophthalmol.2025.0349. PMC 11950975. PMID 40146102.
  29. ^ "American Society of Anesthesiologists Consensus-Based Guidance on Preoperative Management of Patients (Adults and Children) on Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists". asahq.org (Press release). American Society of Anesthesiologists Consensus. 2023.
  30. ^ Kerem, Liya; Stokar, Joshua (December 2024). "Risk of Suicidal Ideation or Attempts in Adolescents With Obesity Treated With GLP1 Receptor Agonists". JAMA Pediatrics. 178 (12): 1307–1315. doi:10.1001/jamapediatrics.2024.3812. PMC 11581746. PMID 39401009.
  31. ^ Mundell, Ernie (2024-10-14). "GLP-1 Weight-Loss Meds Won't Raise Teens' Suicide Risk, May Even Lower It". www.healthday.com. Retrieved 2024-10-18.
  32. ^ "GLP-1 therapy may reduce suicidal ideation risk for adolescents with obesity". www.healio.com. Retrieved 2024-10-18.
  33. ^ Wang, William; Volkow, Nora D.; Berger, Nathan A.; Davis, Pamela B.; Kaelber, David C.; Xu, Rong (January 2024). "Association of semaglutide with risk of suicidal ideation in a real-world cohort". Nature Medicine. 30 (1): 168–176. doi:10.1038/s41591-023-02672-2. PMC 11034947. PMID 38182782.
  34. ^ a b Xie, Yan; Choi, Taeyoung; Al-Aly, Ziyad (March 2025). "Mapping the effectiveness and risks of GLP-1 receptor agonists". Nature Medicine. 31 (3): 951–962. doi:10.1038/s41591-024-03412-w. PMID 39833406.
  35. ^ Bezin, Julien; Gouverneur, Amandine; Pénichon, Marine; Mathieu, Clément; Garrel, Renaud; Hillaire-Buys, Dominique; Pariente, Antoine; Faillie, Jean-Luc (2023-02-01). "GLP-1 Receptor Agonists and the Risk of Thyroid Cancer". Diabetes Care. 46 (2): 384–390. doi:10.2337/dc22-1148. PMID 36356111.
  36. ^ Morales, Daniel R.; Bu, Fan; Viernes, Benjamin; DuVall, Scott L.; Matheny, Michael E.; Simon, Katherine R.; Falconer, Thomas; Richter, Lauren R.; Ostropolets, Anna; Lau, Wallis C.Y.; Man, Kenneth K.C.; Chattopadhyay, Shounak; Mathioudakis, Nestoras; Minty, Evan; Nishimura, Akihiko; Sun, Feng; Yin, Can; Seager, Sarah L.; Chai, Yi; Zhou, Jin J.; Lu, Yuan; Reyes, Carlen; Pistillo, Andrea; Duarte-Salles, Talita; Blacketer, Clair; Schuemie, Martijn J.; Ryan, Patrick B.; Krumholz, Harlan M.; Hripcsak, George; Khera, Rohan; Suchard, Marc A. (August 2025). "Risk of Thyroid Tumors With GLP-1 Receptor Agonists: A Retrospective Cohort Study". Diabetes Care. 48 (8): 1386–1394. doi:10.2337/dc25-0154. PMC 12281980. PMID 40465422.
  37. ^ Pollack, Rena; Stokar, Joshua (2025). "Long-Term Glucagon-Like Peptide 1 Receptor Agonist Use Is Not Associated With Increased Risk of Thyroid Cancer in Adults With Type 2 Diabetes". Diabetes/Metabolism Research and Reviews. 41 (8) e70104. doi:10.1002/dmrr.70104. PMC 12582397. PMID 41182904.
  38. ^ Yang, Chun-Ting; Yao, Wen-Yu; Ou, Huang-Tz; Kuo, Shihchen (April 2023). "Value of GLP-1 receptor agonists versus long-acting insulins for type 2 diabetes patients with and without established cardiovascular or chronic kidney diseases: A model-based cost-effectiveness analysis using real-world data". Diabetes Research and Clinical Practice. 198 110625. doi:10.1016/j.diabres.2023.110625. PMID 36924833.
  39. ^ Moore, Peyton W.; Malone, Kevin; VanValkenburg, Delena; et al. (2023). "GLP-1 Agonists for Weight Loss: Pharmacology and Clinical Implications". Advances in Therapy. 40 (3): 723–742. doi:10.1007/s12325-022-02394-w. PMID 36566341.
  40. ^ Lim, Francesca; Bellows, Brandon K.; Tan, Sarah Xinhui; et al. (2023). "Cost-Effectiveness of Pharmacotherapy for the Treatment of Obesity in Adolescents". JAMA Network Open. 6 (8): e2329178. doi:10.1001/jamanetworkopen.2023.29178. PMC 10472196. PMID 37651143.
  41. ^ "FDA Approves New Treatment for Type 2 Diabetes". FDA.gov (Press release). Food and Drug Administration. 25 January 2010. Archived from the original on 28 January 2010.
  42. ^ "FDA approves Trulicity to treat type 2 diabetes" (Press release). Food and Drug Administration. 18 September 2014. Archived from the original on 18 September 2014.
  43. ^ Tibble, Courtney Aavang; Cavaiola, Tricia Santos; Henry, Robert R (May 2013). "Longer acting GLP-1 receptor agonists and the potential for improved cardiovascular outcomes: a review of current literature". Expert Review of Endocrinology & Metabolism. 8 (3): 247–259. doi:10.1586/eem.13.20. PMID 30780817.
  44. ^ Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, et al. (August 2021). "Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes". The New England Journal of Medicine. 385 (6): 503–515. doi:10.1056/NEJMoa2107519. PMID 34170647.
  45. ^ "Drug Approval Package". www.accessdata.fda.gov. Archived from the original on 2025-04-19. Retrieved 2025-05-01.
  46. ^ Busko, Marlene (15 April 2014). "FDA Approves Weekly Injectable Diabetes Drug: Albiglutide". Medscape (News, FDA Approvals).
  47. ^ "FDA approves Adlyxin to treat type 2 diabetes" (Press release). Food and Drug Administration. 28 July 2016. Archived from the original on December 11, 2019.
  48. ^ Goldenberg, Ronald M.; Gilbert, Jeremy D.; Manjoo, Priya; et al. (2024). "Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high-dose GLP-1 receptor agonists and GLP-1 receptor-based co-agonists". Obesity Reviews. 25 (3) e13663. doi:10.1111/obr.13663. PMID 37968541.
  49. ^ Han, Sabrina H; Safeek, Rachel; Ockerman, Kyle; Trieu, Nhan; Mars, Patricia; Klenke, Audrey; Furnas, Heather; Sorice-Virk, Sarah (14 December 2023). "Public Interest in the Off-Label Use of Glucagon-like Peptide 1 Agonists (Ozempic) for Cosmetic Weight Loss: A Google Trends Analysis". Aesthetic Surgery Journal. 44 (1): 60–67. doi:10.1093/asj/sjad211. PMID 37402640.
  50. ^ Messer, Sarah; Kindelan, Katie (May 18, 2023). "Woman says she got less expensive drug for weight loss after being denied by insurance". abcnews.go.com. ABC News. Retrieved 31 July 2024.
  51. ^ Lovelace, Berkeley Jr. (May 3, 2023). "Safety worries over copycat versions of Ozempic and Wegovy prompt state crackdowns". nbcnews.com. NBC News. Retrieved 26 September 2023.
  52. ^ Jones, C. T. (8 June 2023). "The FDA Warned Ozempic Users. They Don't Give a F-ck". Rolling Stone. Retrieved 26 September 2023.
  53. ^ Gilbert, Daniel (19 September 2023). "Inside the gold rush to sell cheaper imitations of Ozempic". Washington Post. Retrieved 31 July 2024.
  54. ^ Lovelace, Berkeley Jr.; Lewis, Reynolds; Kopf, Marina (19 March 2023). "The high price of Ozempic is pushing many to unregulated, copycat drugs for weight loss". nbcnews.com. NBC News. Retrieved 31 July 2024.
  55. ^ Chiappini, Stefania; Papanti Pelletier, G. Duccio; Vickers-Smith, Rachel; et al. (19 October 2023). "Exploring the nexus of binge eating disorder (BED), New Psychoactive Substances (NPS), and misuse of pharmaceuticals: charting a path forward". Expert Opinion on Pharmacotherapy. 24 (18): 1915–1918. doi:10.1080/14656566.2023.2271389. hdl:2299/26958. PMID 37853742.
  56. ^ FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize
  57. ^ Sydney Lupkin (May 30, 2024). "Compounding pharmacies are making their own versions of blockbuster weight loss drugs". NPR.
  58. ^ Sydney Lupkin (June 7, 2024). "Thinking of buying Wegovy online? Here's what to know about compounding pharmacies". NPR.
  59. ^ a b c d e f g Molteni, Megan; Chen, Elaine (September 30, 2023). "GLP-1 drugs are transforming diabetes, obesity and more. Could a Nobel be next?". STAT News. Retrieved October 16, 2024.
  60. ^ a b c d e Schwarcz, Joe (May 26, 2023). "The Right Chemistry: How the Gila monster assisted weight-loss research". The Montreal Gazette. Retrieved October 16, 2024.
  61. ^ a b c d e f Winkler, Rolfe; Cohen, Ben (June 23, 2023). "Monster Diet Drugs Like Ozempic Started With Actual Monsters". The Wall Street Journal. Retrieved October 16, 2024.
  62. ^ Pollack, Andrew (September 21, 2002). "Eli Lilly in Deal For the Rights To a New Drug For Diabetes". The New York Times. p. C1.
  63. ^ Pollack, Andrew (April 30, 2005). "Lizard-Derived Diabetes Drug Is Approved by the F.D.A.". The New York Times. Retrieved November 2, 2024.
  64. ^ Staton T (November 8, 2011). "Amylin gets Byetta custody in split with Lilly". Fierce Pharma. Retrieved November 2, 2024.
  65. ^ Lovelace Jr., Berkeley (June 23, 2024). "Beyond Ozempic: New GLP-1 drugs promise weight loss and health benefits". NBC News.
  66. ^ Wainer, David (July 19, 2024). "Rivals Emerge to Ozempic and Zepbound—but With a Lag". The Wall Street Journal.
  67. ^ a b Wass, Sanne; Kresge, Naomi (April 30, 2024). "The Ozempic Effect: How a Weight Loss Wonder Drug Gobbled Up an Entire Economy". Bloomberg.
  68. ^ a b Nelson, Eshe (April 20, 2024). "How Ozempic Is Transforming a Small Danish Town". The New York Times.
  69. ^ Barnes, Oliver (October 2, 2024). "Can Eli Lilly become the first $1tn drugmaker?". Financial Times.
  70. ^ Castellana, Marco; Cignarelli, Angelo; Brescia, Francesco; et al. (2019). "GLP -1 receptor agonist added to insulin versus basal-plus or basal-bolus insulin therapy in type 2 diabetes: A systematic review and meta-analysis". Diabetes/Metabolism Research and Reviews. 35 (1) e3082. doi:10.1002/dmrr.3082. PMID 30270567.
  71. ^ Holst, Jens Juul; Jepsen, Sara Lind; Modvig, Ida (2022). "GLP-1 – Incretin and pleiotropic hormone with pharmacotherapy potential. Increasing secretion of endogenous GLP-1 for diabetes and obesity therapy". Current Opinion in Pharmacology. 63 102189. doi:10.1016/j.coph.2022.102189. PMID 35231672.
  72. ^ Pedrosa, Maurício Reis; Franco, Denise Reis; Gieremek, Hannah Waisberg; Vidal, Camila Maia; Bronzeri, Fernanda; de Cassia Rocha, Alexia; de Carvalho Cara, Luis Gabriel; Fogo, Sofia Lenzi; Eliaschewitz, Freddy Goldberg (November 2022). "GLP-1 Agonist to Treat Obesity and Prevent Cardiovascular Disease: What Have We Achieved so Far?". Current Atherosclerosis Reports. 24 (11): 867–884. doi:10.1007/s11883-022-01062-2. PMID 36044100.
  73. ^ Rahmani, Ali Reza; Kalogeropoulos, Andreas P. (2025). "GLP-1 Receptor Agonists in Heart Failure". Biomolecules. 15 (10): 1403. doi:10.3390/biom15101403. PMC 12562493. PMID 41154632.
  74. ^ Wang, Lindsey; Xu, Rong; Kaelber, David C.; Berger, Nathan A. (5 July 2024). "Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes". JAMA Network Open. 7 (7): e2421305. doi:10.1001/jamanetworkopen.2024.21305. PMC 11227080. PMID 38967919.
  75. ^ Cooper, Daniel H.; Ramachandra, Ranuk; Ceban, Felicia; Di Vincenzo, Joshua D.; Rhee, Taeho Greg; Mansur, Rodrigo B.; Teopiz, Kayla M.; Gill, Hartej; Ho, Roger; Cao, Bing; Lui, Leanna M.W.; Jawad, Muhammad Youshay; Arsenault, Juliet; Le, Gia Han; Ramachandra, Diluk; Guo, Ziji; McIntyre, Roger S. (August 2023). "Glucagon-like peptide 1 (GLP-1) receptor agonists as a protective factor for incident depression in patients with diabetes mellitus: A systematic review". Journal of Psychiatric Research. 164: 80–89. doi:10.1016/j.jpsychires.2023.05.041. PMID 37331261.
  76. ^ Pozzi, Marco; Mazhar, Faizan; Peeters, Gabriëlla G.A.M.; Vantaggiato, Chiara; Nobile, Maria; Clementi, Emilio; Radice, Sonia; Carnovale, Carla (October 2019). "A systematic review of the antidepressant effects of glucagon-like peptide 1 (GLP-1) functional agonists: Further link between metabolism and psychopathology". Journal of Affective Disorders. 257: 774–778. doi:10.1016/j.jad.2019.05.044. PMID 31153593.
  77. ^ Klausen, Mette Kruse; Thomsen, Morgane; Wortwein, Gitta; Fink-Jensen, Anders (2022). "The role of glucagon-like peptide 1 (GLP-1) in addictive disorders". British Journal of Pharmacology (Themed issue review). 179 (4). Wiley: 625–641. doi:10.1111/bph.15677. PMC 8820218. PMID 34532853.
  78. ^ Da Porto, Andrea; Casarsa, Viviana; Colussi, Gianluca; et al. (July 2020). "Dulaglutide reduces binge episodes in type 2 diabetic patients with binge eating disorder: A pilot study". Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 14 (4): 289–292. doi:10.1016/j.dsx.2020.03.009. PMID 32289741.
  79. ^ Richards, Jesse; Bang, Neha; Ratliff, Erin L.; et al. (September 2023). "Successful treatment of binge eating disorder with the GLP-1 agonist semaglutide: A retrospective cohort study". Obesity Pillars. 7 100080. doi:10.1016/j.obpill.2023.100080. PMC 10661993. PMID 37990682.

Further reading

[edit]