Exenatide Use in the Management of Type 2 Diabetes Mellitus

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2016 Oct 8

PMID 27713366

Citations 8

Authors

Angelos Kyriacou

Abu Baker Ahmed

Affiliations

Soon will be listed here.

Abstract

Exenatide is a GLP-1 (glucagon-like peptide-1) agonist that has been approved in the UK for use in the management of Type 2 Diabetes Mellitus (T2DM) since 2006. It acts by increasing glucose-induced insulin release and by reducing glucagon secretion postprandially. It therefore increases insulin secretion and reduces glucose levels, especially postprandially. It also reduces gastric emptying and acts centrally to promote satiety. In clinical practice it reduces HbA1c (range; -0.4% to -1.3%), fasting and postprandial blood glucose levels and is the only antidiabetic agent (together with liraglutide; a human GLP-1 analogue) to promote weight loss (range; -1.5 kg to -5.5 kg). It can be used as monotherapy or in combination with metformin and/or sulphonylureas (SU) and/or thiazolinediones (TZD). When compared with insulin it causes similar reductions in HbA1c and glucose levels, but unlike insulin it has the advantage of inducing weight loss. Its main side effect is gastrointestinal (GI) disturbances; nausea is the commonest GI adverse effect, albeit usually mild and transient. Hypoglycaemia is uncommon, especially when used as monotherapy or in combination with metformin. In this review article we scrutinize the currently available evidence for use of exenatide in the management of T2DM.

Citing Articles

Targeting GLP-1 receptors to reduce nicotine use disorder: Preclinical and clinical evidence.

Herman R, Schmidt H Physiol Behav. 2024; 281:114565.

PMID: 38663460 PMC: 11128349. DOI: 10.1016/j.physbeh.2024.114565.

Multifaceted Roles of GLP-1 and Its Analogs: A Review on Molecular Mechanisms with a Cardiotherapeutic Perspective.

Pandey S, Mangmool S, Parichatikanond W Pharmaceuticals (Basel). 2023; 16(6).

PMID: 37375783 PMC: 10304636. DOI: 10.3390/ph16060836.

Effect of Sitagliptin Glibenclamide on Glycemic Markers, Lipid Profile Inflammatory and Oxidative Stress Factors in Type 2 Diabetes Patients: a Double-Blinded Randomized Controlled Trial.

Hematyar J, Rashidi H, Zakerkish M, Payami S, Ghaderian S Maedica (Bucur). 2023; 17(4):762-770.

PMID: 36818268 PMC: 9923081. DOI: 10.26574/maedica.2022.17.4.762.

GLP-1 and Intestinal Diseases.

Hunt J, Holst J, Jeppesen P, Kissow H Biomedicines. 2021; 9(4).

PMID: 33916501 PMC: 8067135. DOI: 10.3390/biomedicines9040383.

Intermittent Use of a Short-Course Glucagon-like Peptide-1 Receptor Agonist Therapy Limits Adverse Cardiac Remodeling via Parkin-dependent Mitochondrial Turnover.

Germano J, Huang C, Sin J, Song Y, Tucker K, Taylor D Sci Rep. 2020; 10(1):8284.

PMID: 32427925 PMC: 7237417. DOI: 10.1038/s41598-020-64924-2.

References

Schwartz S, Kohl B . Type 2 diabetes mellitus and the cardiometabolic syndrome: impact of incretin-based therapies. Diabetes Metab Syndr Obes. 2011; 3:227-42. PMC: 3047965. DOI: 10.2147/dmsott.s11389. View

Linnebjerg H, Kothare P, Park S, Mace K, Reddy S, Mitchell M . Effect of renal impairment on the pharmacokinetics of exenatide. Br J Clin Pharmacol. 2007; 64(3):317-27. PMC: 2000650. DOI: 10.1111/j.1365-2125.2007.02890.x. View

Kendall D, Riddle M, Rosenstock J, Zhuang D, Kim D, Fineman M . Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005; 28(5):1083-91. DOI: 10.2337/diacare.28.5.1083. View

Buse J, Henry R, Han J, Kim D, Fineman M, Baron A . Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004; 27(11):2628-35. DOI: 10.2337/diacare.27.11.2628. View

Viswanathan P, Chaudhuri A, Bhatia R, Al-Atrash F, Mohanty P, Dandona P . Exenatide therapy in obese patients with type 2 diabetes mellitus treated with insulin. Endocr Pract. 2007; 13(5):444-50. DOI: 10.4158/EP.13.5.444. View

Zinman B, Hoogwerf B, Garcia S, Milton D, Giaconia J, Kim D . The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2007; 146(7):477-85. DOI: 10.7326/0003-4819-146-7-200704030-00003. View

McCall A, Cox D, Brodows R, Crean J, Johns D, Kovatchev B . Reduced daily risk of glycemic variability: comparison of exenatide with insulin glargine. Diabetes Technol Ther. 2009; 11(6):339-44. PMC: 2768873. DOI: 10.1089/dia.2008.0107. View

Creutzfeldt W, Ebert R, Nauck M, Stockmann F . Disturbances of the entero-insular axis. Scand J Gastroenterol Suppl. 1983; 82:111-9. View

Drucker D, Nauck M . The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006; 368(9548):1696-705. DOI: 10.1016/S0140-6736(06)69705-5. View

10.

Vilsboll T, Krarup T, Deacon C, Madsbad S, Holst J . Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 2001; 50(3):609-13. DOI: 10.2337/diabetes.50.3.609. View

11.

Nauck M, Stockmann F, Ebert R, Creutzfeldt W . Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986; 29(1):46-52. DOI: 10.1007/BF02427280. View

12.

Buse J, Rosenstock J, Sesti G, Schmidt W, Montanya E, Brett J . 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. DOI: 10.1016/S0140-6736(09)60659-0. View

13.

Kim D, MacConell L, Zhuang D, Kothare P, Trautmann M, Fineman M . Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care. 2007; 30(6):1487-93. DOI: 10.2337/dc06-2375. View

14.

Ranta F, Avram D, Berchtold S, Dufer M, Drews G, Lang F . Dexamethasone induces cell death in insulin-secreting cells, an effect reversed by exendin-4. Diabetes. 2006; 55(5):1380-90. DOI: 10.2337/db05-1220. View

15.

Davies M, Donnelly R, Barnett A, Jones S, Nicolay C, Kilcoyne A . Exenatide compared with long-acting insulin to achieve glycaemic control with minimal weight gain in patients with type 2 diabetes: results of the Helping Evaluate Exenatide in patients with diabetes compared with Long-Acting insulin (HEELA) study. Diabetes Obes Metab. 2009; 11(12):1153-62. PMC: 2810445. DOI: 10.1111/j.1463-1326.2009.01154.x. View

16.

Tripathy N, Basha S, Jain R, Shetty S, Ramachandran A . Exenatide and acute pancreatitis. J Assoc Physicians India. 2009; 56:987-8. View

17.

Yoon N, Cavaghan M, Brunelle R, Roach P . Exenatide added to insulin therapy: a retrospective review of clinical practice over two years in an academic endocrinology outpatient setting. Clin Ther. 2009; 31(7):1511-23. DOI: 10.1016/j.clinthera.2009.07.021. View

18.

Bergenstal R, Lewin A, Bailey T, Chang D, Gylvin T, Roberts V . Efficacy and safety of biphasic insulin aspart 70/30 versus exenatide in subjects with type 2 diabetes failing to achieve glycemic control with metformin and a sulfonylurea. Curr Med Res Opin. 2009; 25(1):65-75. DOI: 10.1185/03007990802597951. View

19.

Ratner R, Maggs D, Nielsen L, Stonehouse A, Poon T, Zhang B . Long-term effects of exenatide therapy over 82 weeks on glycaemic control and weight in over-weight metformin-treated patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2006; 8(4):419-28. DOI: 10.1111/j.1463-1326.2006.00589.x. View

20.

Cvetkovic R, Plosker G . Exenatide: a review of its use in patients with type 2 diabetes mellitus (as an adjunct to metformin and/or a sulfonylurea). Drugs. 2007; 67(6):935-54. DOI: 10.2165/00003495-200767060-00008. View