Статті в журналах: "Glucagon-like peptide analogues"

1

Zhang, Yifan, and Wengen Chen. "Radiolabeled glucagon-like peptide-1 analogues." Nuclear Medicine Communications 33, no. 3 (March 2012): 223–27. http://dx.doi.org/10.1097/mnm.0b013e32834e7f47.

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Gupta, Vishal. "Glucagon-like peptide-1 analogues: An overview." Indian Journal of Endocrinology and Metabolism 17, no. 3 (2013): 413. http://dx.doi.org/10.4103/2230-8210.111625.

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3

Nilsson, Peter M. "Hemodynamic effects by glucagon-like peptide-1 receptor analogues." Journal of Hypertension 35, no. 5 (May 2017): 953–54. http://dx.doi.org/10.1097/hjh.0000000000001315.

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4

Wilding, John P. H., and Kevin Hardy. "Glucagon-like peptide-1 analogues for type 2 diabetes." BMJ 342 (2011): d410. http://dx.doi.org/10.1136/bmj.d410.

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5

Chun, Hyun-Ji, and Hyuk-Sang Kwon. "Clinical Efficacy of Glucagon Like Peptide-1 (GLP-1) Analogues." Journal of Korean Diabetes 14, no. 3 (2013): 125. http://dx.doi.org/10.4093/jkd.2013.14.3.125.

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6

Gallwitz, Baptist. "Glucagon-like Peptide–1 Analogues for Type 2 Diabetes Mellitus." Drugs 71, no. 13 (September 2011): 1675–88. http://dx.doi.org/10.2165/11592810-000000000-00000.

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7

Dharmaraj, B. "A brief review on newer Glucagon like Peptide-1 analogues." International Journal of Preclinical and Clinical Research 1, no. 1 (December 21, 2020): 26–34. http://dx.doi.org/10.51131/ijpccr/v1i1.7.

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GLP-1 (Glucagon like Peptide-1) receptor agonists have been shown to be effective in the treatment of type 2 diabetes mellitus (T2DM). Although the first GLP-1 receptor agonist, Exenatide, was approved in the year 2000, other agents with a longer duration of action that do not require twice-daily dosing are now being developed. Indeed, Liraglutide, a once-daily GLP-1 receptor agonist, was approved in 2010, a once-weekly extended-release formulation of Exenatide (Exenatide ER) was approved in 2011 and now more recently Semaglutide, an oral GLP 1 receptor agonist was approved for medical use in the United States in September 2019 and in the European Union in April 2020. The importance of GLP-1 itself and the use of GLP-1 receptor agonists in T2DM are discussed. An overview of the clinical development of the GLP-1 receptor agonists (Exenatide ER, Liraglutide, Lixisenatide, Albiglutide, Taspoglutide and Semaglutide) is provided and their mechanism of action, efficacy in terms of glycaemic control, weight loss and tolerability are reviewed. Keywords: GLP1 receptor agonist; Liraglutide; Exenatide ER; Lixisenatide; Semaglutide

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8

Iacobellis, Gianluca. "Can epicardial fat glucagon-like peptide-1 receptor open up to the cardiovascular benefits of glucagon-like peptide-1 analogues?" Polish Archives of Internal Medicine 131, no. 3 (March 30, 2021): 224–25. http://dx.doi.org/10.20452/pamw.15904.

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9

Juul Holst, Jens. "Glucagon-like Peptide-1, A Gastrointestinal Hormone with a Pharmaceutical Potential." Current Medicinal Chemistry 6, no. 11 (November 1999): 1005–17. http://dx.doi.org/10.2174/092986730611220401163238.

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Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone secreted from endocrine cells in the gut mucosa in response to meal ingestion. It is an important incretin hormone; mice with a null mutation in the GLP-1 receptor gene develop glucose intolerance. In addition, it inhibits gastrointestinal secretion and motility and is thought to be part of the "ileal brake" mechanism. Perhaps because of the latter actions it inhibits food intake, but intracerebral injection of GLP-1 also inhibits food intake. The insu linotropic effect is preserved in patients with type 2 diabetes mellitus, in whom also glucagon secretion is inhibited. Thus upon iv GLP-1 infusion blood glucose may be completely normalised. Because its actions are glucose-dependent hypoglycaemia does not develop. However, GLP-1 is metabolised extremely rapidly in vivo, initially by a mechanism that involves the enzyme dipeptidyl peptidase-IV. It is currently being investigated how GLP-1 or analogues thereof can be employed in practical diabetes therapy. Promising solutions include the development of stable analogues and inhibitors of the degrading enzyme.

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Williams, David M., Matthew Staff, Stephen C. Bain, and Thinzar Min. "Glucagon-like Peptide-1 Receptor Analogues for the Treatment of Obesity." Endocrinology 18, no. 1 (2022): 43. http://dx.doi.org/10.17925/ee.2022.18.1.43.

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There is an increasing prevalence of obesity worldwide, associated with significant morbidity and mortality, which frequently reduces quality of life and life expectancy. Consequently, there is a substantial and growing personal and economic burden necessitating the development of more effective therapies for obesity. Glucagon-like peptide-1 receptor analogues (GLP-1RAs) are licensed for the treatment of type 2 diabetes (T2D), and there is substantial evidence that these drugs not only improve cardiovascular outcomes but also promote weight loss. More recent evidence supports the use of the GLP-1RAs liraglutide and semaglutide in people with obesity without T2D. This article discusses the results of the major cardiovascular outcome trials for GLP-1RAs in people with T2D, the SCALE Obesity and Prediabetes study (Effect of liraglutide on body weight in non-diabetic obese subjects or overweight subjects with co-morbidities: SCALE™ - Obesity and Pre-diabetes; ClinicalTrials.gov identifier: NCT01272219; investigating liraglutide) and the STEP studies (Semaglutide treatment effect in people with obesity; assorted studies; investigating subcutaneous semaglutide). We also highlight the importance of a cost-effective approach to obesity pharmacotherapy. Clinicians should consider the use of GLP-1RAs in people with obesity, especially those with T2D or other obesity-related diseases, such as hypertension and dyslipidaemia. Ongoing trials, as well as clinical and cost-effectiveness appraisals, are anticipated over the next 12 months, and their findings may change the current landscape of obesity pharmacotherapy.

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Welling, Mila Sofie, Cornelis J. de Groot, Lotte Kleinendorst, Bibian van der Voorn, Jan Steven Burgerhart, Eline S. van der Valk, Mieke M. van Haelst, Erica L. T. van den Akker, and Elisabeth F. C. van Rossum. "Effects of Glucagon-Like-Peptide-1 Analogue Treatment in Genetic Obesity." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A33—A34. http://dx.doi.org/10.1210/jendso/bvab048.065.

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Abstract Introduction: Obesity is highly prevalent, comes with serious health burden and is difficult to treat. In a minority, there is a genetic cause for the obesity. In these patients, therapy-resistant obesity is often observed despite intensive lifestyle treatment. Moreover, it is still unclear whether bariatric surgery is less successful in genetic obesity. Liraglutide is a Glucagon-Like-Peptide-1 (GLP-1) receptor agonist or GLP-1 analogue, showing positive effects on metabolic parameters, satiety and weight loss in lifestyle-induced obesity. We present our experiences of GLP-1 analogue treatment in patients with genetic obesity disorders. Methods: Adults with overweight or severe obesity and a molecularly proven genetic cause were treated with liraglutide 3,0 mg daily, in addition to ongoing intensive supportive lifestyle treatment. Anthropometrics, metabolic parameters, resting energy expenditure (REE), side effects, and subjectively reported satiety and quality of life were assessed. Results: Two patients with a heterozygous pathogenic melanocortin 4 recepter variant and two patients with 16p11.2 deletion syndrome, ranging in age between 21 and 32 years and in BMI between 28.1 and 55.7 kg/m2 at baseline, were treated. At end of follow-up, ranging between 33 weeks and 12 years, a mean change in BMI and waist circumference was observed of -5.7 ± 3.8 kg/m2 and -15.2 ± 21.1 cm, respectively. All patients reported better quality of life, three of them also reported improved satiety. Moreover, improvement of metabolic parameters was seen. No clear effect on REE was observed. Two patients experienced mild side effects, e.g. nausea and stomach pain, for a brief period. Conclusion: We here show beneficial effects of GLP-1 analogues on weight, metabolic parameters, and quality of life in four patients with genetic obesity. Satiety improved in three of the four patients. All patient achieved at least the clinically relevant 5–10% weight loss. Our findings suggest that GLP-1 analogue treatment might be an effective treatment option, in addition to a healthy lifestyle, for patients with genetic obesity.

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12

Suntsov, Yury Ivanovich. "Modern antihyperglycemic agents prescribed in Russia for type 2 diabetes mellitus." Diabetes mellitus 15, no. 1 (March 15, 2012): 6–9. http://dx.doi.org/10.14341/2072-0351-5971.

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Aims. To conduct an analysis of modern antihyperglycemic prescription patterns in type 2 diabetes mellitus (T2DM). Materials and methods. Russian DM State registry was studied. Results. We obtained absolute and comparative data on use of insulin analogues, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 agonists in treatment of T2DM. Conclusion. Percentage of DPP-4 inhibitors and GLP-1 analogues in T2DM treatment patterns remains nominal and does not exceed0.2%, which is significantly lower than in the majority of other countries. Insulin analogues are prescribed considerably more frequentlyand currently appear to be the most promising agents for treatment of T2DM.

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13

Bielka, Weronika, Agnieszka Przezak, Maria Salmanowicz, and Bolesław Banach. "Possibilities of using analogues of glucagon-like peptide-1 in various disease entities." Farmacja Polska 77, no. 1 (February 24, 2021): 48–55. http://dx.doi.org/10.32383/farmpol/133606.

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14

Yellon, DerekM, MarynaV Basalay, and SeanM Davidson. "Can glucagon-like peptide-1 (GLP-1) analogues make neuroprotection a reality?" Neural Regeneration Research 15, no. 10 (2020): 1852. http://dx.doi.org/10.4103/1673-5374.280313.

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15

Armstrong, Matthew J. "Glucagon-like peptide-1 analogues in nonalcoholic steatohepatitis: From bench to bedside." Clinical Liver Disease 10, no. 2 (August 2017): 32–35. http://dx.doi.org/10.1002/cld.650.

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16

Claus, Thomas H., Clark Q. Pan, Joanne M. Buxton, Ling Yang, Jennifer C. Reynolds, Nicole Barucci, Michael Burns, et al. "Dual-acting peptide with prolonged glucagon-like peptide-1 receptor agonist and glucagon receptor antagonist activity for the treatment of type 2 diabetes." Journal of Endocrinology 192, no. 2 (February 2007): 371–80. http://dx.doi.org/10.1677/joe-06-0018.

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Type 2 diabetes is characterized by reduced insulin secretion from the pancreas and overproduction of glucose by the liver. Glucagon-like peptide-1 (GLP-1) promotes glucose-dependent insulin secretion from the pancreas, while glucagon promotes glucose output from the liver. Taking advantage of the homology between GLP-1 and glucagon, a GLP-1/glucagon hybrid peptide, dual-acting peptide for diabetes (DAPD), was identified with combined GLP-1 receptor agonist and glucagon receptor antagonist activity. To overcome its short plasma half-life DAPD was PEGylated, resulting in dramatically prolonged activity in vivo. PEGylated DAPD (PEG-DAPD) increases insulin and decreases glucose in a glucose tolerance test, evidence of GLP-1 receptor agonism. It also reduces blood glucose following a glucagon challenge and elevates fasting glucagon levels in mice, evidence of glucagon receptor antagonism. The PEG-DAPD effects on glucose tolerance are also observed in the presence of the GLP-1 antagonist peptide, exendin(9–39). An antidiabetic effect of PEG-DAPD is observed in db/db mice. Furthermore, PEGylation of DAPD eliminates the inhibition of gastrointestinal motility observed with GLP-1 and its analogues. Thus, PEG-DAPD has the potential to be developed as a novel dual-acting peptide to treat type 2 diabetes, with prolonged in vivo activity, and without the GI side-effects.

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Price, Samantha L., James S. Minnion, and Stephen R. Bloom. "Investigating the Glucagon Receptor and Glucagon-Like Peptide 1 Receptor Activity of Oxyntomodulin-Like Analogues in Male Wistar Rats." Current Therapeutic Research 77 (December 2015): 111–15. http://dx.doi.org/10.1016/j.curtheres.2015.10.003.

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Su, Yunfang, Zijuan Zhang, Hao Li, Jinlian Ma, Limin Sun, Simai Shao, Zhenqiang Zhang, and Christian Hölscher. "A GLP-2 Analogue Protects SH-SY5Y and Neuro-2a Cells Against Mitochondrial Damage, Autophagy Impairments and Apoptosis in a Parkinson Model." Drug Research 71, no. 01 (October 6, 2020): 43–50. http://dx.doi.org/10.1055/a-1266-3263.

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AbstractGlucagon-like peptide-2 (GLP-2) is a peptide hormone that belongs to the glucagon-derived peptide family. We have previously shown that analogues of the sister hormone Glucagon-like peptide-1 (GLP-1) showed neuroprotective effects. Here we investigated the effect of a GLP-2 agonist in a cell model of Parkinsonʼs disease (PD) created by treating SH-SY5Y or Neuro-2a cells with 1-Methyl-4-phenyl-pyridine ion (MPP+). Cell viability and cell cytotoxicity was detected by MTT and LDH assays, respectively. The protein expression levels of mitochondrial, autophagy and apoptotic biomarkers including PGC-1α, Mfn2, IRE1, ATG7, LC3B, Beclin1 and Bcl-2 were detected by western blot. Mitochondrial superoxide was detected by MitoSOX Red. In addition, mitochondrial morphology, autophagosome and apoptotic corpuscles were observed by transmission electron microscope (TEM). We found that the GLP-1 and the GLP-2 agonists both protect cells against mitochondrial damage, autophagy impairments and apoptosis induced by MPP+both in SH-SY5Y and Neuro-2a cells. Cell signaling for mitogenesis was enhanced, and oxidative stress levels much reduced by the drugs. This demonstrates for the first time the neuroprotective effects of a GLP-2 analogue in PD cellular models, in which oxidative stress, autophagy and apoptosis play crucial roles. The protective effects were comparable to those seen with the GLP-1 analogue liraglutide. The results suggest that not only GLP-1, but also GLP-2 has neuroprotective properties and may be useful as a novel treatment of PD.

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Xiao, Q., J. Giguere, M. Parisien, W. Jeng, S. A. St-Pierre, P. L. Brubaker, and M. B. Wheeler. "Biological Activities of Glucagon-Like Peptide-1 Analogues in Vitro and in Vivo." Biochemistry 40, no. 9 (March 2001): 2860–69. http://dx.doi.org/10.1021/bi0014498.

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Kelly, Erik M., and Donald E. Cutlip. "Diabetes Drugs and Cardiovascular Event Reduction: A Paradigm Shift." US Cardiology Review 12, no. 1 (March 15, 2018): 46–50. http://dx.doi.org/10.15420/usc.2017:35:1.

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This review article summarizes the recent cardiovascular outcome data for sodium–glucose cotransporter-2 inhibitors and glucagon-like peptide-1 analogues, which have been found to reduce cardiovascular events. We also detail the implications these new medications will have on clinical practice through a review of recent diabetes guidelines and cost-effectiveness data.

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Sawamura, Toshitaka, Shigehiro Karashima, Ai Ohmori, Kei Sawada, Mitsuhiro Kometani, Yoshiyu Takeda, and Takashi Yoneda. "Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome Worsen after the Administration of Dulaglutide." Medicina 58, no. 2 (February 14, 2022): 289. http://dx.doi.org/10.3390/medicina58020289.

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Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical polyarthritis and limb pitting edema. Although the detailed mechanisms of this syndrome have not been clearly understood, some agents including dipeptidyl peptidase-4 inhibitors have been reported to induce RS3PE syndrome. However, glucagon-like peptide-1 (GLP-1) analogues have not been reported to be associated with this syndrome. A 91-year-old woman was admitted to our hospital with complaints of severe polyarthritis and limb edema. She was diagnosed with RS3PE syndrome. Oral prednisolone improved her symptoms. However, her symptoms worsened after the administration of dulaglutide, with elevated serum inflammatory markers. Discontinuation of dulaglutide without additional treatment improved her symptoms and laboratory findings. This case might indicate the possibility of development and worsening of RS3PE syndrome caused after GLP-1 analogue.

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Kim, Ki-Suk, and Hyeung-Jin Jang. "Medicinal Plants Qua Glucagon-Like Peptide-1 Secretagogue via Intestinal Nutrient Sensors." Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/171742.

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Glucagon-like peptide-1 (GLP-1) participates in glucose homeostasis and feeding behavior. Because GLP-1 is rapidly inactivated by the enzymatic cleavage of dipeptidyl peptidase-4 (DPP4) long-acting GLP-1 analogues, for example, exenatide and DPP4 inhibitors, for example, liraglutide, have been developed as therapeutics for type 2 diabetes mellitus (T2DM). However, the inefficient clinical performance and the incidence of side effects reported on the existing therapeutics for T2DM have led to the development of a novel therapeutic strategy to stimulate endogenous GLP-1 secretion from enteroendocrine L cells. Since the GLP-1 secretion of enteroendocrine L cells depends on the luminal nutrient constituents, the intestinal nutrient sensors involved in GLP-1 secretion have been investigated. In particular, nutrient sensors for tastants, cannabinoids, and bile acids are able to recognize the nonnutritional chemical compounds, which are abundant in medicinal plants. These GLP-1 secretagogues derived from medicinal plants are easy to find in our surroundings, and their effectiveness has been demonstrated through traditional remedies. The finding of GLP-1 secretagogues is directly linked to understanding of the role of intestinal nutrient sensors and their recognizable nutrients. Concurrently, this study demonstrates the possibility of developing novel therapeutics for metabolic disorders such as T2DM and obesity using nutrients that are readily accessible in our surroundings.

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Korbut, Anton Ivanovich, and Vadim Valerievich Klimontov. "Incretin-based therapy: renal effects." Diabetes mellitus 19, no. 1 (January 13, 2016): 53–63. http://dx.doi.org/10.14341/dm7727.

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Glucagon like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors are new classes of hypoglycemic agents with numerous pleiotropic effects. The review summarises data about the influence of GLP-1 analogues and DPP-4 inhibitors on structural and functional changes in diabetic kidneys. Growing evidence indicates that the kidney is one of the loci of the effects and degradation of GLP-1. The potency of the effects of GLP-1 in diabetic kidneys can be reduced by decrease in GLP-1 receptor expression or enhancement of GLP-1 degradation. In experimental models of diabetic nephropathy and non-diabetic renal injury, GLP-1 analogues and DPP-4 inhibitors slow the development of kidney fibrosis and prevent the decline of kidney function. The mechanisms of protective effect include hyperglycaemia reduction, enhancement of sodium excretion, suppression of inflammatory and fibrogenic signalling pathways, reduction of oxidative stress and apoptosis in the kidneys. In clinical studies, the urinary albumin excretion reduction rate while using the GLP-1 analogue and DPP-4 inhibitor treatment was demonstrated in patients with type 2 diabetes. Long-term impact of these agents on renal function in diabetes needs further investigations.

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24

Zhou, Jinpei, Shuaijian Ni, Huibin Zhang, Hai Qian, Yushi Chi, Wenlong Huang, Lu Yu, Xiaowen Hu, and Wei Chen. "Synthesis and Bioactivity Evaluation of Dipeptidyl Peptidase IV Resistant Glucagon-like Peptide-1 Analogues." Protein & Peptide Letters 17, no. 10 (October 1, 2010): 1290–95. http://dx.doi.org/10.2174/092986610792231546.

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Ebdrup, Björn H., Filip K. Knop, Pelle L. Ishoy, Egill Rostrup, Birgitte Fagerlund, Henrik Lublin, and Birte Glenthøj. "Poster #218 GLUCAGON-LIKE PEPTIDE-1 ANALOGUES AGAINST ANTIPSYCHOTIC-INDUCED OVERWEIGHT: POTENTIAL PHYSIOLOGICAL BENEFITS." Schizophrenia Research 136 (April 2012): S264. http://dx.doi.org/10.1016/s0920-9964(12)70789-2.

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Hantouche, Christine M., Khalil M. Bitar, Georges M. Nemer, Mounir Y. Obeid, Lina N. Kadi, Asdghig H. Der-Boghossian, and Anwar B. Bikhazi. "Role of glucagon-like peptide-1 analogues on insulin receptor regulation in diabetic rat hearts." Canadian Journal of Physiology and Pharmacology 88, no. 1 (January 2010): 54–63. http://dx.doi.org/10.1139/y09-095.

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This study focused on the regulation and affinity modulation of the insulin receptor of coronary endothelium and cardiomyocytes in nondiabetic and STZ-induced type 1 diabetic rats. Male rats were divided into the following 9 groups: nondiabetic (N), nondiabetic treated with exendin-4 (NE), nondiabetic treated with dipeptidyl peptidase IV (DPP-IV) inhibitor (NDp), diabetic (D), diabetic treated with insulin (DI), diabetic treated with exendin-4 (DE), diabetic co-treated with insulin and exendin-4 (DIE), diabetic treated with DPP-IV inhibitor (DDp), and diabetic co-treated with insulin and DPP-IV inhibitor (DIDp). After the rats were treated for 1 month, a first-order Bessel function was employed to estimate the insulin binding affinity (with time constant τ = 1/k−n) to its receptors on the coronary endothelium and cardiomyocytes using CHAPS-untreated and CHAPS-treated heart perfusion, respectively. The results showed that diabetes (D) decreased the τ value on the coronary endothelium and increased it on cardiomyocytes compared with the nondiabetic group (N). Treatment with insulin and (or) exendin-4, a glucagon-like peptide-1 (GLP-1) analogue, increased τ on the coronary endothelium only. On the coronary endothelium, τ values of DI and DIDp were normalized. Western blots of the insulin receptor showed upregulation in D, downregulation in DI, and normalization in DE and DDp. Immunohistochemistry and RT-PCR findings indicated atrial natriuretic factor (ANF) in all diabetic ventricles, thus ascertaining hypertrophy. Therefore, negative myocardial effects related to the insulin receptor were diminished in diabetic rats treated with DPP-IV inhibitor and, more efficiently, by exendin-4.

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Zalunin, I. A., A. S. Asrarkulova, and D. G. Kozlov. "Incretin Analogues in Therapy of Type 2 Diabetes and Obesity." Biotekhnologiya 37, no. 3 (2021): 53–64. http://dx.doi.org/10.21519/0234-2758-2021-37-3-53-64.

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Type 2 diabetes is one the most common metabolic diseases, which are obviously the price to pay for lifestyle changes in most people. Dangerous in itself, this disease provokes other metabolic disorders such as obesity, and neurodegenerative diseases, such as Alzheimer's disease. Pharmacologists are very active in creating drugs for these illnesses. The design of synthetic highly active analogues of incretins, peptide hormones produced by neuroendocrine cells, is one of the most promising research areas. Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide are the best known incretin hormones. Analogues of the first peptide have already found application in medical practice. The next step in the creation of drugs for diabetes was the development of polyagonists, which combine the properties of several different peptide hormones responsible for glucose homeostasis. The combination of the properties of incretins gives hopes for a synergism net effect. In the past few years, the creation of such coagonists has been very fast. In some cases, the results of clinical trials have already been obtained; however, they often contradict each other. Making clear this difficult situation was the main motivation for writing the present review. incretins, glucan-like peptide-1, glucose-dependant insulintropic polypeptide, agonism, antagonism, type 2 diabetes, obesity

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Liu, Hongbin, Anthony E. Dear, Lotte B. Knudsen, and Richard W. Simpson. "A long-acting glucagon-like peptide-1 analogue attenuates induction of plasminogen activator inhibitor type-1 and vascular adhesion molecules." Journal of Endocrinology 201, no. 1 (January 9, 2009): 59–66. http://dx.doi.org/10.1677/joe-08-0468.

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Glucagon-like peptide-1 (GLP-1) administration attenuates endothelial cell dysfunction in diabetic patients and inhibits tumour necrosis factor α (TNF)-mediated plasminogen activator inhibitor type-1 (PAI-1) induction in human vascular endothelial cells. The short half-life of GLP-1 mediated via degradation by the enzyme dipeptidyl peptidase 4 mandates the clinical use of long-acting GLP-1 analogues. The effects of a long-acting GLP-1 analogue on PAI-1 and vascular adhesion molecule expression in vascular endothelial cells are unknown. In this report, we demonstrate for the first time that the treatment with liraglutide, a long-acting GLP-1 analogue, inhibited TNF or hyperglycaemia-mediated induction of PAI-1, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 mRNA and protein expression in a human vascular endothelial cell line. In addition, treatment attenuated TNF- or hyperglycaemia-mediated induction of the orphan nuclear receptor Nur77 mRNA expression. Taken together, these observations indicate that liraglutide inhibits TNF- or glucose-mediated induction of PAI-1 and vascular adhesion molecule expression, and this effect may involve the modulation of NUR77. These effects suggest that liraglutide may potentially improve the endothelial cell dysfunction associated with premature atherosclerosis identified in type 2 diabetic patients.

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Holst, Jens Juul. "Pharmacology of GLP-1-based therapies." British Journal of Diabetes & Vascular Disease 8, no. 2_suppl (November 2008): S10—S18. http://dx.doi.org/10.1177/1474651408100523.

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Glucagon-like peptide-1 GLP-1 is a naturally occurring 30-amino acid peptide synthesised in intestinal endocrine L cells. GLP-1 mediates glucose homeostasis through stimulation of glucose-dependent insulin secretion, biosynthesis of insulin and inhibition of glucagon secretion. These effects have potential clinical value in type 2 diabetes. However, because native GLP-1 is rapidly degraded to its inactive form by dipeptidyl peptidase-4 (DPP-4), it has a short half-life in vivo . Strategies to overcome this therapeutic limitation include developing GLP-1 mimetics and analogues with longer half-lives and to inhibit DPP-4. Exenatide (exendin-4) is a 39-amino acid peptide originally derived from the venom of the Gila monster lizard, and shares a 53% sequence identity with human GLP-1. Exenatide has a longer circulating half-life, reflecting relative resistance to DPP-4 degradation, and is administered twice daily. Liraglutide is a once-daily human GLP-1 analogue with high (97%) sequence identity. The specific structural modifications that characterise liraglutide result in increased self-association (allowing slow absorption from the subcutaneous depot), promote albumin binding and reduce susceptibility to DPP-4, giving liraglutide a half-life of 13 hours after once-daily administration. Preliminary studies of exenatide and liraglutide show clinically relevant reductions in glycosylated haemoglobin A1c (HbA1c) compared with placebo, without hypoglycaemia and with weight loss of up to 3 kg. DPP-4 inhibitors, such as vildagliptin (not available in the USA) and sitagliptin can help stabilise postprandial GLP-1 levels and thus produce desirable effects on insulin and glucagon production. The potential for weight reduction with DPP-4 inhibitors appears limited, perhaps reflecting the limited increase in GLP-1 levels achieved with these agents.Br J Diabetes Vasc Dis, 2008;8 (Suppl 2) : S10—S18

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Saraceni, Christine, and Tom L. Broderick. "Effects of Glucagon-Like Peptide-1 and Long-Acting Analogues on??Cardiovascular and Metabolic Function." Drugs in R & D 8, no. 3 (2007): 145–53. http://dx.doi.org/10.2165/00126839-200708030-00002.

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Manavi, Mohammad Amin. "Neuroprotective effects of glucagon-like peptide-1 (GLP-1) analogues in epilepsy and associated comorbidities." Neuropeptides 94 (August 2022): 102250. http://dx.doi.org/10.1016/j.npep.2022.102250.

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Fink-Jensen, Anders, and T. Vilsbøll. "Glucagon-like peptide-1 (GLP-1) analogues: A potential new treatment for alcohol use disorder?" Nordic Journal of Psychiatry 70, no. 8 (May 6, 2016): 561–62. http://dx.doi.org/10.1080/08039488.2016.1176252.

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ELBANA, M.D., KHALED A. "Effect of Glucagon Like Peptide 1| (GLP1) Analogues on Obese Egyptians With and Without Diabetes." Medical Journal of Cairo University 87, September (September 1, 2019): 3205–8. http://dx.doi.org/10.21608/mjcu.2019.65613.

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Engeli, Stefan, and Jens Jordan. "Blood pressure effects of glucagon-like peptide 1 analogues and sodium glucose transporter 2 inhibitors." Current Opinion in Nephrology and Hypertension 23, no. 5 (September 2014): 468–72. http://dx.doi.org/10.1097/01.mnh.0000449846.91046.ac.

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Batista, Andre F., Victor Bodart-Santos, Fernanda G. De Felice, and Sergio T. Ferreira. "Neuroprotective Actions of Glucagon-Like Peptide-1 (GLP-1) Analogues in Alzheimer’s and Parkinson’s Diseases." CNS Drugs 33, no. 3 (December 3, 2018): 209–23. http://dx.doi.org/10.1007/s40263-018-0593-6.

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Atila, Cihan, Thilo Burkard, Andrea Meienberg, Nica Jeanloz, Tanja Vukajlovic, Katja Bologna, Michelle Steinmetz, et al. "RF32 | PSUN59 Glucagon-Like Peptide-1 Analogues: A New Way to Quit Smoking? SKIP – a Randomised Controlled Study." Journal of the Endocrine Society 6, Supplement_1 (November 1, 2022): A261. http://dx.doi.org/10.1210/jendso/bvac150.536.

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Abstract Background Cigarette smoking is the leading preventable cause of premature death. Despite dedicated programs, quit rates remain low due to barriers such as nicotine withdrawal syndrome or post-cessation weight gain. Glucagon-like peptide-1 (GLP-1) analogues reduce energy intake and body weight and seem to modulate addictive behavior. These GLP-1 properties are of major interest in the context of smoking cessation. The aim of this study was to evaluate the GLP-1 analogue dulaglutide as a new therapy for smoking cessation. Methods This was a placebo-controlled, double-blind, parallel group, superiority, single-center randomized study including 255 patients. The intervention consisted of a 12-week treatment phase with dulaglutide 1.5 mg or placebo injected subcutaneously at a weekly study visit, in addition to standard of care (behavioral counselling and pharmacotherapy with varenicline). Point-prevalence abstinence rate at week 12 as primary outcome was assessed by self-reported smoking status and biochemical confirmation by end-expiratory exhaled carbon monoxide measurement. We further investigated weight gain and changes in the glucose homeostasis at week 12. In a substudy (n=71), we compared behavioral (i.e., nicotine craving measured by a Visual Analogue Scale from 1-7) and brain activity changes in response to smoking cue videos using functional magnetic resonance imaging (fMRI) at baseline and week 12. Results The point-prevalence abstinence rate after 12 weeks of treatment was 80/127 (63%) in the dulaglutide group and 82/128 (65%) in the placebo group (difference in proportions [95% CI] -1.9% [-10.7, 14.4], p=0.859). We observed an increase in weight in the placebo (+1.8kg [SD 2.4]) and a decrease in the dulaglutide group (-0.7kg [SD 3.3]) between baseline and week 12; baseline-adjusted difference in weight change [95% CI] -2.5kg [-3.3, -1.7], p<0.001. Craving in response to smoking cue videos decreased from baseline to week 12 (estimated mean difference [95% CI] -3.0 [-3.7, -2.3], p<0.001), with no difference between dulaglutide and placebo (estimated mean difference [95% CI] 0.4 [-1.2, 2.0], p=0.6). Similarly, no difference in whole brain functional activity was seen between the two treatments, at both time points and between baseline and follow up. Conclusion In this study, an exceptional high point prevalence abstinence rate in both groups was observed, most probably due to the very close (weekly) supervision of the patients. Our data provides no evidence that dulaglutide modulates nicotine craving or smoking cessation rates. Nevertheless, GLP-1 analogues such as dulaglutide may be a promising treatment during smoking cessation as it may avoid post-cessation weight gain. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:24 p.m. - 1:29 p.m.

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Iacobellis, Gianluca, Vladimir Camarena, David Sant, and Gaofeng Wang. "Human Epicardial Fat Expresses Glucagon-Like Peptide 1 and 2 Receptors Genes." Hormone and Metabolic Research 49, no. 08 (May 17, 2017): 625–30. http://dx.doi.org/10.1055/s-0043-109563.

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AbstractEpicardial adipose tissue (EAT) is an easily measurable visceral fat of the heart with unique anatomy, functionality, and transcriptome. EAT can serve as a therapeutic target for pharmaceutical agents targeting the fat. Glucagon-like peptide-1 (GLP-1) and GLP-2 analogues are newer drugs showing beneficial cardiovascular and metabolic effects. Whether EAT expresses GLP- 1 and 2 receptors (GLP-1R and GLP-2R) is unknown. RNA-seq analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to evaluate the presence of GLP-1R and GLP-2R in EAT and subcutaneous fat (SAT) obtained from 8 subjects with coronary artery disease and type 2 diabetes mellitus undergoing elective cardiac surgery. Immunofluorescence was also performed on EAT and SAT samples using Mab3f52 against GLP-1R. Our RNA-sequencing (RNA-seq) analysis showed that EAT expresses both GLP-1R and GLP-2R genes. qRT-PCR analysis confirmed that GLP-1R expression was low but detected by 2 different sets of intron-spanning primers. GLP-2R expression was detected in all patients and was found to be 5-fold higher than GLP-1R. The combination of accurately spliced reads from RNA-seq and successful amplification using intron-spanning primers indicates that both GLP-1R and GLP-2R are expressed in EAT. Immunofluorescence clearly showed that GLP-1R is present and more abundant in EAT than SAT. This is the first time that human EAT is found to express both GLP-1R and GLP-2R genes. Pharmacologically targeting EAT may induce beneficial cardiovascular and metabolic effects.

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Ji, Chenhui, Guo-Fang Xue, Guanglai Li, Dongfang Li, and Christian Hölscher. "Neuroprotective effects of glucose-dependent insulinotropic polypeptide in Alzheimer’s disease." Reviews in the Neurosciences 27, no. 1 (January 1, 2016): 61–70. http://dx.doi.org/10.1515/revneuro-2015-0021.

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AbstractGlucose-dependent insulinotropic polypeptide (GIP) is a member of the incretin hormones and growth factors. Neurons express the GIP receptor, and GIP and its agonists can pass through the blood brain barrier and show remarkable neuroprotective effects by protecting synapse function and numbers, promoting neuronal proliferation, reducing amyloid plaques in the cortex and reducing the chronic inflammation response of the nervous system. Long-acting analogues of GIP that are protease resistant had been developed as a treatment for type 2 diabetes. It has been found that such GIP analogues show good protective effects in animal models of Alzheimer’s disease. Novel dual agonist peptides that activate the GIP receptor and another incretin receptor, glucagon-like peptide -1 (GLP-1), are under development that show superior effects in diabetic patients compared to single GLP-1 agonists. The dual agonists also show great promise in treating neurodegenerative disorders, and there are currently several clinical trials ongoing, testing GLP-1 mimetics in people with Alzheimer’s or Parkinson’s disease.

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Green, BD, MH Mooney, VA Gault, N. Irwin, CJ Bailey, P. Harriott, B. Greer, FP O'Harte, and PR Flatt. "N-terminal His(7)-modification of glucagon-like peptide-1(7-36) amide generates dipeptidyl peptidase IV-stable analogues with potent antihyperglycaemic activity." Journal of Endocrinology 180, no. 3 (March 1, 2004): 379–88. http://dx.doi.org/10.1677/joe.0.1800379.

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Glucagon-like peptide-1(7-36)amide (GLP-1) possesses several unique and beneficial effects for the potential treatment of type 2 diabetes. However, the rapid inactivation of GLP-1 by dipeptidyl peptidase IV (DPP IV) results in a short half-life in vivo (less than 2 min) hindering therapeutic development. In the present study, a novel His(7)-modified analogue of GLP-1, N-pyroglutamyl-GLP-1, as well as N-acetyl-GLP-1 were synthesised and tested for DPP IV stability and biological activity. Incubation of GLP-1 with either DPP IV or human plasma resulted in rapid degradation of native GLP-1 to GLP-1(9-36)amide, while N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 were completely resistant to degradation. N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 bound to the GLP-1 receptor but had reduced affinities (IC(50) values 32.9 and 6.7 nM, respectively) compared with native GLP-1 (IC(50) 0.37 nM). Similarly, both analogues stimulated cAMP production with EC(50) values of 16.3 and 27 nM respectively compared with GLP-1 (EC(50) 4.7 nM). However, N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 exhibited potent insulinotropic activity in vitro at 5.6 mM glucose (P<0.05 to P<0.001) similar to native GLP-1. Both analogues (25 nM/kg body weight) lowered plasma glucose and increased plasma insulin levels when administered in conjunction with glucose (18 nM/kg body weight) to adult obese diabetic (ob/ob) mice. N-pyroglutamyl-GLP-1 was substantially better at lowering plasma glucose compared with the native peptide, while N-acetyl-GLP-1 was significantly more potent at stimulating insulin secretion. These studies indicate that N-terminal modification of GLP-1 results in DPP IV-resistant and biologically potent forms of GLP-1. The particularly powerful antihyperglycaemic action of N-pyroglutamyl-GLP-1 shows potential for the treatment of type 2 diabetes.

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GÓRSKA, ALEKSANDRA, and MARCIN B. ARCISZEWSKI. "Distribution and function of glucagon-like peptide 1 (GLP-1) in the digestive tract of mammals and the clinical use of its analogues." Medycyna Weterynaryjna 76, no. 07 (2023): 6374–2023. http://dx.doi.org/10.21521/mw.6374.

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Recently, interest in glucagon-like peptide-1 (GLP-1) and other peptides derived from preproglucagon has increased significantly. GLP-1 is a 30-amino acid peptide hormone produced in L-type enteroendocrine cells as a response to food intake. GLP-1 is rapidly metabolized and inactivated by the dipeptidyl peptidase IV enzyme before the hormone leaves the intestine, which increases the likelihood that GLP-1 action is transmitted through sensory neurons in the intestine and liver through the GLP-1 receptor. The main actions of GLP-1 are to stimulate insulin secretion (i.e. act as incretin hormone) and inhibit glucagon secretion, thus contributing to the reduction of postprandial glucose spikes. GLP-1 also inhibits motility and gastrointestinal secretion, and therefore acts as part of the „small bowel brake” mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake. Because of these effects, GLP-1 or GLP-1 receptor agonists are now increasingly used to treat type 2 diabetes. Reduced GLP-1 secretion may contribute to the development of obesity, and excessive secretion may be responsible for postprandial reactive hypoglycemia. The use of GLP-1 agonists opens up new possibilities for the treatment of type 2 diabetes and other metabolic diseases. In the last two decades, many interesting studies covering both the physiological and pathophysiological role of GLP-1 have been published, and our understanding of GLP-1 has broadened significantly. In this review article, we have tried to describe our current understanding of how GLP-1 works as both a peripheral hormone and as a central neurotransmitter in health and disease. We focused on its biological effects on the body and the potential clinical application in relation to current research.

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L A, Maheswary, Dr Silvia Navis, Anusree S, and Dr Prasobh G.R. "Role of Glucagon-Like Peptide-1 Analogues on Obesity and Type-II Diabetes Mellitus: A Review." International Journal of Pharmaceutical Sciences Review and Research 64, no. 2 (October 20, 2020): 102–8. http://dx.doi.org/10.47583/ijpsrr.2020.v64i02.017.

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Han, Jing, Yue Huang, Xinyu Chen, Feng Zhou, Yingying Fei, and Junjie Fu. "Rational design of dimeric lipidated Xenopus glucagon-like peptide 1 analogues as long-acting antihyperglycaemic agents." European Journal of Medicinal Chemistry 157 (September 2018): 177–87. http://dx.doi.org/10.1016/j.ejmech.2018.07.072.

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Pizzoferrato, Marco, Pierluigi Puca, Sara Ennas, Giovanni Cammarota, and Luisa Guidi. "Glucagon-like peptide-2 analogues for Crohn’s disease patients with short bowel syndrome and intestinal failure." World Journal of Gastroenterology 28, no. 44 (November 28, 2022): 6258–70. http://dx.doi.org/10.3748/wjg.v28.i44.6258.

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44

Ruyatkina, Lyudmila Alexandrovna, and Maxim Sorokin. "Combined insulin detemir and liraglutide therapy in type 2 diabetic patients: a base for an alliance." Diabetes mellitus 20, no. 2 (June 20, 2017): 142–50. http://dx.doi.org/10.14341/7875.

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Combined glucose-lowering therapy, comprising of basal insulin with glucagon-like peptide-1 (GLP-1) analogues, has become central to the treatment of type 2 diabetes both at the start of insulin therapy, and as an alternative to basal-bolus insulin. The combination of insulin detemir (insulin analogue) with liraglutide (GLP-1 analogue) reduces fasting and postprandial glycaemia, lowers the risk of hypoglycaemia and does not have a negative impact on body weight. In this literature review, the pharmacodynamic and pharmacokinetic profiles, as well as the potential benefits of combined insulin detemir and liraglutide therapy on diabetic nephropathy and high cardiovascular disease risk were determined. Data from randomised clinical trials and the National Registry were used to assess the clinical efficacy of combined insulin detemir and liraglutide therapy. The different mechanistic actions of insulin detemir and liraglutide resulted in an additive glucose-lowering effect, which did not affect the pharmacodynamic and pharmacokinetic profiles of each therapeutic agent.

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Carydias, Elisabeth, Andoneta Tasho, Chara Kani, Flora Bacopoulou, Charikleia Stefanaki, and Sophia L. Markantonis. "Systematic Review and Meta-Analysis of the Efficacy and Safety of Metformin and GLP-1 Analogues in Children and Adolescents with Diabetes Mellitus Type 2." Children 9, no. 10 (October 18, 2022): 1572. http://dx.doi.org/10.3390/children9101572.

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Diabetes mellitus type 2 (DMT2) is one of the most frequent glucose metabolism disorders, in which serum glucose concentrations are increased. In most cases, changes in lifestyle and diet are considered as the first step in addressing its therapy. If changes in lifestyle and diet fail, drugs, such as metformin, must be added. Lately, apart from metformin or insulin, the FDA has approved the use of glucagon-like peptide-1 (GLP-1) analogues for children and adolescents. Little is known about their efficacy and safety at this young age. The main aim of this systematic review/meta-analysis was to assess the safety and efficacy of metformin and GLP-1 analogues, exenatide and liraglutide, compared with placebos or other antidiabetic drugs used for DMT2 in children and adolescents. Metformin did not seem to demonstrate pharmacologic superiority, while GLP-1 analogues were found superior to placebos. GLP-1 analogues may be considered a useful alternative for the treatment of DMT2 in children and adolescents.

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46

Bratilova, E. S., V. A. Kachnov, V. V. Tyrenko, I. S. Zheleznyak, D. V. Cherkashin, S. V. Kushnarev, and A. D. Sobolev. "Fat depot of the heart: contribution to the development of cardiovascular diseases, visualization methods and the possibilities of it’s correction." Bulletin of the Russian Military Medical Academy 22, no. 3 (December 15, 2020): 211–16. http://dx.doi.org/10.17816/brmma50562.

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Abstract. Рresents the possibilities of various visualization methods for assessing heart fat depot in patients with cardiovascular disease, as well as the effect of adipose tissue on myocardial function. The prospects of using the heart fat depot as a therapeutic target are considered on the example of the successful use of various groups of antidiabetic drugs, in particular glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Thus, it has been established that an ectopic fat depot makes a certain contribution to atherogenesis due to its effect on lipid metabolism, participation in the formation of a chronic inflammatory reaction of low intensity, potentiation of endothelial dysfunction, and activation of a coagulant shift. In addition, local organ dysfunctions, such as increased intrarenal pressure, mitochondrial disorders, increased lipogenesis, the formation of insulin resistance and lipotoxicity additionally create prerequisites for an increase in cardiovascular risk. Defines diagnostic and useful methods that not only quantitatively, but also qualitatively describe the relationship of fat depot and potential comorbid pathology. The effect of reducing cardiovascular risk, consisting in reducing the amount of epicardial adipose tissue in the studied, was observed when taking the preparation of the biguanide group, as well as its combination with drugs - analogues of glucagon-like peptide 1 and dipeptidyl peptidase-4 inhibitor. A similar effect was also observed in the case of the use of type 2 sodium-glucose cotransporter-2 inhibitors.

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Li, X. n., H. m. Bu, X. h. Ma, Sh Lu, Sh Zhao, Y. l. Cui, and J. Sun. "Glucagon-like Peptide-1 Analogues Inhibit Proliferation and Increase Apoptosis of Human Prostate Cancer Cells in vitro." Experimental and Clinical Endocrinology & Diabetes 125, no. 02 (December 22, 2016): 91–97. http://dx.doi.org/10.1055/s-0042-112368.

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Wiśniewski, Kazimierz, Javier Sueiras-Diaz, Guangcheng Jiang, Robert Galyean, Mark Lu, Dorain Thompson, Yung-Chih Wang, et al. "Synthesis and Pharmacological Characterization of Novel Glucagon-like Peptide-2 (GLP-2) Analogues with Low Systemic Clearance." Journal of Medicinal Chemistry 59, no. 7 (March 25, 2016): 3129–39. http://dx.doi.org/10.1021/acs.jmedchem.5b01909.

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Cary, Brian P., Marlies V. Hager, and Samuel H. Gellman. "Impact of Substitution Registry on the Receptor‐Activation Profiles of Backbone‐Modified Glucagon‐like Peptide‐1 Analogues." ChemBioChem 20, no. 22 (September 20, 2019): 2834–40. http://dx.doi.org/10.1002/cbic.201900300.

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50

Xiao, Jianzhong, and Wenying Yang. "Weight Loss Is Still an Essential Intervention in Obesity and its Complications: A Review." Journal of Obesity 2012 (2012): 1–6. http://dx.doi.org/10.1155/2012/369097.

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The prevalence of obesity is more than 20% in many developed countries and it increases in developing countries. Obesity is associated with metabolic disorders, cardiovascular diseases, pulmonary diseases, digestive diseases, and cancers. Although other specific treatments for these complications exist, weight loss is still an essential intervention in obesity and its complications. Therapeutic life change, behavior modification, pharmacotherapy, and surgery are major approaches to weight loss. In addition, medicine used in diabetes such as Glucagon-like peptide-1 analogues may be a new type of medicine for obesity, at least for those obese patients with diabetes.

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