The Safety and Efficacy of Glucagon-Like Peptide-1 Receptor Agonist Drugs: A Comprehensive Literature Review

Authors

  • Khalid M. Alhusayni Department of Pharmacy, King Abdulaziz Hospital, Taif City, Saudi Arabia
  • Abdulmajeed M. Aljuaid Department of Pharmacy, King Abdulaziz Hospital, Taif City, Saudi Arabia
  • Abdulaziz M. Alkhammash Department of Medical Supply, King Abdulaziz Hospital, Taif City, Saudi Arabia
  • Shahad A. Alzahrani Nahdi Medical Company, Makkah, Saudi Arabia
  • Abeer K. Alorabi Department of Pharmacy, King Abdulaziz Hospital, Taif City, Saudi Arabia
  • Yasmin B. Alotaibi College of Pharmacy, Taif University, Taif City, Saudi Arabia
  • Nidaa T. Alhumaidi College of Pharmacy, Taif University, Taif City, Saudi Arabia
  • Waad K. Alharbi Nahdi Medical Company, Makkah, Saudi Arabia
  • Ghaliah A. Harbi Alnahdi Medical Company, Riyadh City, Saudi Arabia
  • Ibrahim Alzahrani King Abdulaziz Hospital, Jeddah City, Saudi Arabia

DOI:

https://doi.org/10.3889/oamjms.2023.11735

Keywords:

type 2 diabetes mellitus, obesity, hypoglycemia, GLP-1RA-, antihyperglycemic

Abstract

There is a new class of antihyperglycemic medications called glucagon-like peptide-1 receptor agonists (GLP-1RAs). They work by increasing the effects of insulin on peripheral tissues, decreasing the liver’s glucose production, improving satiety through central nervous system action, as well as encouraging appropriate pancreatic cell production and (glucagon) suppression. GLP-1 agonists are a group of drugs used to manage type 2 diabetes mellitus and promote weight reduction. However, they cause several unfavorable side effects such as diarrhea, constipation, nausea, and vomiting, as expected. After extensive research, several clinical studies have found them to be safe for the heart and kidneys. Moreover, patients with a history of pancreatitis are advised to avoid GLP-1RA-based treatments, even though there is insufficient information to determine whether there is a causal relationship.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Secher A, Jelsing J, Baquero AF, Hecksher-Sørensen J, Cowley MA, Dalbøge LS, et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Invest. 2014;124(10):4473-88. https://doi.org/10.1172/JCI75276 PMid:25202980 DOI: https://doi.org/10.1172/JCI75276

Holst JJ. From the incretin concept and the discovery of GLP-1 to today’s diabetes therapy. Front Endocrinol (Lausanne). 2019;10:260. https://doi.org/10.3389/fendo.2019.00260 PMid:31080438 DOI: https://doi.org/10.3389/fendo.2019.00260

Kugler AJ, Thiman ML. Efficacy and safety profile of once- weekly dulaglutide in Type 2 diabetes: A report on the emerging new data. Diabetes Metab Syndr Obes. 2018;11:187-97. https://doi.org/10.2147/DMSO.S134960 PMid:29780260 DOI: https://doi.org/10.2147/DMSO.S134960

Mahapatra MK, Karuppasamy M, Sahoo BM. Therapeutic potential of semaglutide, a newer GLP-1 receptor agonist, in abating obesity, non-alcoholic steatohepatitis and neurodegenerative diseases: A narrative review. Pharm Res. 2022;39(6):1233-48. https://doi.org/10.1007/s11095-022-03302-1 PMid:35650449 DOI: https://doi.org/10.1007/s11095-022-03302-1

Hunt B, Malkin SJ, Moes RG, Huisman EL, Vandebrouck T, Wolffenbuttel BH. Once-weekly semaglutide for patients with Type 2 diabetes: A cost-effectiveness analysis in the Netherlands. BMJ Open Diabetes Res Care. 2019;7(1):e000705. https://doi.org/10.1136/bmjdrc-2019-000705 PMid:31641522 DOI: https://doi.org/10.1136/bmjdrc-2019-000705

Burcelin R, Gourdy P. Harnessing glucagon-like peptide-1 receptor agonists for the pharmacological treatment of overweight and obesity. Obes Rev. 2017;18(1):86-98. https://doi.org/10.1111/obr.12465 PMid:27636208 DOI: https://doi.org/10.1111/obr.12465

Sohal DS, Nain PS, Singh P, Ahuja A, Singh A. ABCD score of >6 predicts diabetes remission following bariatric surgery. Int J Diabetes Dev Ctries. 2020;40:416-21. DOI: https://doi.org/10.1007/s13410-020-00801-y

Kanie T, Mizuno A, Takaoka Y, Suzuki T, Yoneoka D, Nishikawa Y, et al. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: A network meta-analysis. Cochrane Database Syst Rev. 2021;10(10):CD013650. https://doi.org/10.1002/14651858.CD013650.pub2 PMid:34693515 DOI: https://doi.org/10.1002/14651858.CD013650.pub2

Estabile PC, Almeida MC, Campagnoli EB, Santo MA, Rodrigues MR, Milléo FQ, et al. Immunohistochemical detection of l cells in gastrointestinal tract mucosa of patients after surgical treatment for control of Type 2 diabetes mellitus. Arq Bras Cir Dig. 2022;35:e1651. https://doi.org/10.1590/0102-672020210002e1651 PMid:35730880 DOI: https://doi.org/10.1590/0102-672020210002e1651

Beiroa D, Imbernon M, Gallego R, Senra A, Herranz D, Villarroya F, et al. GLP-1 agonism stimulates brown adipose tissue thermogenesis and browning through hypothalamic AMPK. Diabetes. 2014;63(10):3346-58. https://doi.org/10.2337/ db14-0302 PMid:24917578 DOI: https://doi.org/10.2337/db14-0302

Zhang W, Bi S. Hypothalamic regulation of brown adipose tissue thermogenesis and energy homeostasis. Front Endocrinol (Lausanne). 2015;6:136. https://doi.org/10.3389/fendo.2015.00136 PMid:26379628 DOI: https://doi.org/10.3389/fendo.2015.00136

Heppner KM, Marks S, Holland J, Ottaway N, Smiley D, Dimarchi R, et al. Contribution of brown adipose tissue activity to the control of energy balance by GLP-1 receptor signalling in mice. Diabetologia. 2015;58(9):2124-32. https://doi.org/10.1007/s00125-015-3651-3 PMid:26049402 DOI: https://doi.org/10.1007/s00125-015-3651-3

Delgado-Aros S, Kim DY, Burton DD, Thomforde GM, Stephens D, Brinkmann BH, et al. Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans. Am J Physiol Gastrointest Liver Physiol. 2002;282(3):G424-31. https://doi.org/10.1152/ajpgi.2002.282.3.G424 PMid:11841992 DOI: https://doi.org/10.1152/ajpgi.2002.282.3.G424

Owens D, Monnier L, Bolli G. Differential effects of GLP-1 receptor agonists on components of dysglycaemia in individuals with Type 2 diabetes mellitus. Diabetes Metab. 2013;39(6):485-96. https://doi.org/10.1016/j.diabet.2013.09.004 PMid:24156868 DOI: https://doi.org/10.1016/j.diabet.2013.09.004

Aroda VR, Ahmann A, Cariou B, Chow F, Davies MJ, Jódar E, et al. Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of Type 2 diabetes: Insights from the SUSTAIN 1-7 trials. Diabetes Metab. 2019;45(5):409-18. https://doi.org/10.1016/j.diabet.2018.12.001 PMid:30615985 DOI: https://doi.org/10.1016/j.diabet.2018.12.001

Poulia KA, Sarantis P, Antoniadou D, Koustas E, Papadimitropoulou A, Papavassiliou AG, et al. Pancreatic cancer and cachexia-metabolic mechanisms and novel insights. Nutrients. 2020;12(6):1543.‏ https://doi.org/10.3390/nu12061543 PMid:32466362 DOI: https://doi.org/10.3390/nu12061543

Ard J, Fitch A, Fruh S, Herman L. Weight loss and maintenance related to the mechanism of action of glucagon-like peptide 1 receptor agonists. Adv Ther. 2021;38(6):2821-39. https://doi.org/10.1007/s12325-021-01710-0 PMid:33977495 DOI: https://doi.org/10.1007/s12325-021-01710-0

Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, et al. Liraglutide once a day versus exenatide twice a day for Type 2 diabetes: A 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet. 2009;374(9683):39-47. https://doi.org/10.1016/S0140-6736(09)60659-0 PMid:19515413 DOI: https://doi.org/10.1016/S0140-6736(09)60659-0

Fonseca VA, Alvarado-Ruiz R, Raccah D, Boka G, Miossec P, Gerich JE, et al. Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: A randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono). Diabetes Care. 2012;35(6):1225-31. https://doi.org/10.2337/dc11-1935 PMid:22432104 DOI: https://doi.org/10.2337/dc11-1935

Jendle J, Grunberger G, Blevins T, Giorgino F, Hietpas RT, Botros FT. Efficacy and safety of dulaglutide in the treatment of Type 2 diabetes: A comprehensive review of the dulaglutide clinical data focusing on the AWARD phase 3 clinical trial program. Diabetes Metab Res Rev. 2016;32(8):776-90. https://doi.org/10.1002/dmrr.2810 PMid:27102969 DOI: https://doi.org/10.1002/dmrr.2810

Chudleigh RA, Bain SC. Semaglutide injection for the treatment of adults with Type 2 diabetes. Expert Rev Clin Pharmacol.

;13(7):675-84. https://doi.org/10.1080/17512433.2020.1776108 PMid:32476529 DOI: https://doi.org/10.1080/17512433.2020.1776108

Davies M, Pieber TR, Hartoft-Nielsen ML, Hansen OK, Jabbour S, Rosenstock J. Effect of oral semaglutide compared with placebo and subcutaneous semaglutide on glycemic control in patients with Type 2 diabetes: A randomized clinical trial. JAMA. 2017;318(15):1460-70. https://doi.org/10.1001/jama.2017.14752 PMid:29049653 DOI: https://doi.org/10.1001/jama.2017.14752

Prasad-Reddy L, Isaacs D. A clinical review of GLP-1 receptor agonists: Efficacy and safety in diabetes and beyond. Drugs Context. 2015;4:212280. https://doi.org/10.7573/dic.212283 PMid:26213556 DOI: https://doi.org/10.7573/dic.212283

Jensterle M, Janež A. Glucagon-like peptide-1 receptor agonists in the treatment of obesity. Horm Res Pædiatr. 2021:1-10. https://doi.org/10.1159/000521264 PMid:34852347 DOI: https://doi.org/10.1159/000521264

Moretto TJ, Milton DR, Ridge TD, Macconell LA, Okerson T, Wolka AM, et al. Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with Type 2 diabetes: A randomized, double-blind, placebo- controlled, parallel-group study. Clin Ther. 2008;30(8):1448-60. https://doi.org/10.1016/j.clinthera.2008.08.006 PMid:18803987 DOI: https://doi.org/10.1016/j.clinthera.2008.08.006

Wilding JP, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. https://doi.org/10.1056/NEJMoa2032183 PMid:33567185 DOI: https://doi.org/10.1056/NEJMoa2032183

Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of Type 2 diabetes - state-of-the- art. Mol Metab. 2021;46:101102. https://doi.org/10.1016/j.molmet.2020.101102 PMid:33068776 DOI: https://doi.org/10.1016/j.molmet.2020.101102

Drucker DJ, Buse JB, Taylor K, Kendall DM, Trautmann M, Zhuang D, et al. Exenatide once weekly versus twice daily for the treatment of Type 2 diabetes: A randomised, open-label, non-inferiority study. Lancet. 2008;372(9645):1240-50. https://doi.org/10.1016/S0140-6736(08)61206-4 PMid:18782641 DOI: https://doi.org/10.1016/S0140-6736(08)61206-4

Wharton S, Davies M, Dicker D, Lingvay I, Mosenzon O, Rubino DM, et al. Managing the gastrointestinal side effects of GLP-1 receptor agonists in obesity: Recommendations for clinical practice. Postgrad Med. 2022;134(1):14-9. shttp://doi.org/10.1080/00325481.2021.2002616 PMid:34775881 DOI: https://doi.org/10.1080/00325481.2021.2002616

Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and Type 2 diabetes (STEP 2): A randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021;397(10278):971-84. https://doi.org/10.1016/S0140-6736(21)00213-0 PMid:33667417 DOI: https://doi.org/10.1016/S0140-6736(21)00213-0

Pratley R, Amod A, Hoff ST, Kadowaki T, Lingvay I, Nauck M, et al. Oral semaglutide versus subcutaneous liraglutide and placebo in Type 2 diabetes (PIONEER 4): A randomised, double-blind, phase 3a trial. Lancet. 2019;394(10192):39-50. https://doi.org/10.1016/S0140-6736(19)31271-1 PMid:31186120 DOI: https://doi.org/10.1016/S0140-6736(19)31271-1

Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, et al. Semaglutide versus dulaglutide once weekly in patients with Type 2 diabetes (SUSTAIN 7): A randomised, open- label, phase 3b trial. Lancet Diabetes Endocrinol. 2018;6(4):275-86. https://doi.org/10.1016/S2213-8587(18)30024-X PMid:29397376 DOI: https://doi.org/10.1016/S2213-8587(18)30024-X

Consoli A, Formoso G. Potential side effects to GLP-1 agonists: Understanding their safety and tolerability. Expert Opin Drug Saf. 2015;14(2):207-18. https://doi.org/10.1517/14740338.2015.987122 PMid:25496749 DOI: https://doi.org/10.1517/14740338.2015.987122

Trujillo JM, Nuffer W, Smith BA. GLP-1 receptor agonists: An updated review of head-to-head clinical studies. Ther Adv Endocrinol Metab. 2021;12:2042018821997320. https://doi.org/10.1177/2042018821997320 PMid:33767808 DOI: https://doi.org/10.1177/2042018821997320

Bergenstal RM, Wysham C, Macconell L, Malloy J, Walsh B, Yan P, et al. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of Type 2 diabetes (DURATION-2): A randomised trial. Lancet. 2010;376(9739):431-9. https://doi.org/10.1016/S0140-6736(10)60590-9 PMid:20580422 DOI: https://doi.org/10.1016/S0140-6736(10)60590-9

Rubino DM, Greenway FL, Khalid U, O’Neil PM, Rosenstock J, Sørrig R, et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: The STEP 8 randomized clinical trial. JAMA. 2022;327(2):138-50. https://doi.org/10.1001/jama.2021.23619 PMid:35015037 DOI: https://doi.org/10.1001/jama.2021.23619

Aroda VR, Henry RR, Han J, Huang W, DeYoung MB, Darsow T, et al. Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: Meta-analysis and systematic review. Clin Ther. 2012;34(6):1247-58.e22. https://doi.org/10.1016/j.clinthera.2012.04.013 PMid:22608780 DOI: https://doi.org/10.1016/j.clinthera.2012.04.013

Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC.

Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology. 2011;141(1):150-6. https://doi.org/10.1053/j.gastro.2011.02.018 PMid:21334333 DOI: https://doi.org/10.1053/j.gastro.2011.02.018

Gourgari E, Huerta-Saenz L, Tonyushkina KN, Rosolowsky ET, Guttmann-Bauman I. Use of glucagon-like peptide-1 receptor agonists for pediatric patients with obesity and diabetes: The providers’ perspectives. Pediatr Diabetes. 2021;22(6):872-5. https://doi.org/10.1111/pedi.13234 PMid:34018306 DOI: https://doi.org/10.1111/pedi.13234

Maideen NM, Balasubramaniam R. Pharmacologically relevant drug interactions of sulfonylurea antidiabetics with common herbs. J Herbmed Pharmacol. 2018;7(3):200-10. DOI: https://doi.org/10.15171/jhp.2018.32

Oliveira EF, Santos-Martins D, Ribeiro AM, Brás NF, Cerqueira NS, Sousa SF, et al. HMG-CoA Reductase inhibitors: An updated review of patents of novel compounds and formulations (2011-2015). Expert Opin Ther Pat. 2016;26(11):1257-72. https://doi.org/10.1080/13543776.2016.1216977 PMid:27537201 DOI: https://doi.org/10.1080/13543776.2016.1216977

Downloads

Published

2023-08-04

How to Cite

1.
Alhusayni KM, Aljuaid AM, Alkhammash AM, Alzahrani SA, Alorabi AK, Alotaibi YB, Alhumaidi NT, Alharbi WK, Harbi GA, Alzahrani I. The Safety and Efficacy of Glucagon-Like Peptide-1 Receptor Agonist Drugs: A Comprehensive Literature Review. Open Access Maced J Med Sci [Internet]. 2023 Aug. 4 [cited 2024 Apr. 28];11(F):286-92. Available from: https://oamjms.eu/index.php/mjms/article/view/11735

Issue

Section

Narrative Review Article

Categories

Similar Articles

You may also start an advanced similarity search for this article.