GuidelinesOther guideline
Drug Summary - GLP-1 Receptor Agonists
Drug summary - GLP-1 Receptor Agonists
(Refer to: Drug review - GLP-1 receptor agonists for drug review and references)
Mode of action and pharmacology | GLP-1 receptor agonists are modified GLP-1 molecules that have structural homology with endogenous GLP-1 but are resistant to the enzymatic cleavage by DPP-4 | ||
| Glycaemic efficacy and indications | Reduces HbA1C by 0.9 to 1.2 % Monotherapy: registered (liraglutide) but not recommended for primary healthcare Dual therapy: registered but not recommended for primary healthcare Triple therapy: Can be combined with any 2 of metformin / sulphonylurea / TZD. Do not combine with DPP-4 inhibitor or SGLT2 inhibitor Exenatide can be as added to basal insulin with or without oral agents | ||
| Macrovascular and Mortality Outcomes | Lixisenatide was neutral in the ELIXA trial Liraglutide and semaglutide have each demonstrated reductions in a composite endpoint of major adverse cardiovascular events by 13% and 26% in the LEADER and SUSTAIN-6 trials respectively (vs. placebo), when used in patients with established cardiovascular disease There are no cardiovascular outcomes trials with exenatide | ||
| Hypoglycaemia | Hypoglycaemia rates are not different to placebo except when GLP-1 receptor agonist are combined with insulin or insulin secretagogues | ||
| Non-glycaemia benefits | Weight reduction of between 1 and 3 kg for exenatide and liraglutide Both exenatide and liraglutide reduce SBP and DBP by 1 to 5 mmHg Reduction in liver fat content (liraglutide) | ||
| Side Effects and Precautions | Nausea and vomiting in up to 25%; Discontinuation rate 5-20% Pancreatitis Skin reactions | ||
| Contraindications | History of pancreatitis, or at high risk for pancreatitis (e.g. untreated gallstone disease, recent or planned ERCP, excessive alcohol use) History of pancreatic tumour History of medullary thyroid cancer (MTC) or multiple endocrine neoplasia (MEN) syndrome type 2 | ||
| Dosing | eGFR | Exenetide | Liraglutide |
| ≥30 ml/min <35 ml/min | Initial dose is 5 ug BD for the 1st month; then 10 ug BD Contraindicated | Initiate 0.6 mg daily Maximum dose of 1.8 mg daily No adjustment | |
| Cost | High (R 620.00 to R 2145.00 - single exit price March 2017) | ||
(See Strength of Recommendations Taxonomy (SORT) for explanation of Grade A-C)
| SEMDSA 2017 Recommendations for GLP-1 receptor agonists (GLP-1RA) | |
Consider a GLP-1RA injectable as the third glucose lowering drug (triple therapy) in overweight and obese patients when glycaemic targets are not being achieved or maintained | A |
Consider adding a GLP-1RA to existing basal insulin therapy (with oral therapies) as an alternative to intensifying the insulin regimen, especially when weight gain and/or hypoglycaemia is a limiting factor | A |
Escalate the dose of GLP-1RA slowly to minimise side-effects | C |
Circumstances where a GLP-1RA may be preferred to other treatment options: Overweight and obese patients Weight gain or hypoglycaemia has been, or is likely to be problematic with other treatment options HbA1C is very high (GLP-1RA and insulin are the most effective glucose lowering drugs for most patients) Patients with established cardiovascular disease (liraglutide benefit); to be managed at specialist care level | C |
Circumstances where a GLP-1RA may not be the preferred option: Patients with chronic gastrointestinal disorders Patients with a history of pancreatitis or pancreatic tumour | C |
Caution:
Do not persist with any chosen treatment if the HbA1C has not decreased by > 0.5% after six months