Glucagon-like peptide-1 analogues for type 2 diabetesBMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d410 (Published 16 February 2011) Cite this as: BMJ 2011;342:d410
- John P H Wilding, professor of medicine1,
- Kevin Hardy, consultant physician2
- 1University of Liverpool Diabetes and Endocrinology Clinical Research Unit, Clinical Sciences Centre, University Hospital Aintree, Liverpool L9 7AL, UK
- 2Diabetes Centre, St Helens Hospital, St Helens WA9 3DA, UK
- Correspondence to: J P H Wilding
A 58 year old woman attends a diabetes clinic with type 2 diabetes of seven years’ duration and no history of macrovascular disease. She is obese (body mass index 37), but says she eats a healthy diet and describes this. Her blood pressure is 134/78 mm Hg, and she has microalbuminuria, but normal renal function and a lipid profile within target levels ranges. She is taking simvastatin 40 mg daily and perindopril 4 mg daily. Glycated haemoglobin (HbA1c) is 8.3% despite treatment with metformin 850 mg three times a day and gliclazide 160 mg twice a day. How would you best manage her hyperglycaemia? (The table⇓ shows the drug treatment options.)
After discussion with the patient of the benefits and risks of the available treatment options (including the “do nothing” option, risks of hypoglycaemia, and effects on body weight), you agree on a glucagon-like peptide-1 (GLP-1) analogue (exenatide or liraglutide).
What are glucagon-like peptide-1 analogues?
Glucagon-like peptide-1 (GLP-1) is a naturally occurring peptide hormone, released from the gut after eating. GLP-1 stimulates insulin release (the incretin effect), suppresses glucagon release (thus reducing hepatic gluconeogenesis), delays gastric emptying, and promotes satiety. Natural GLP-1 has a short half life of a few minutes as a result of breakdown by endopeptidases such as dipeptidyl peptidase-4. GLP-1 analogues, also known as incretin mimetics (exenatide and liraglutide), are modified GLP-1-like peptides that are resistant to degradation by dipeptidyl peptidase-4, with elimination half lives of 2.4 hours and 13 hours respectively. GLP-1 analogues are indicated as an adjunct to other treatments in the management of type 2 diabetes and are given once daily (liraglutide) or twice daily (exenatide) by subcutaneous injection.
How well do GLP-1 analogues work?
Exenatide has been studied in several randomised controlled trials in which either exenatide or placebo was added for up to six months to existing treatment …