Is a preferred 2nd line agent in cardiovascular and renal disease as reduces mortality from cardiovascular events and renal disease progression independent of effects on glycaemic control; and leads to the most weight loss of all of the glucose lowering agents available, blood pressure reduction and will not cause hypoglycaemia in or of itself. Therefore, GLP1 receptor agonists (GLP1RA) should be strongly considered in all patients with diabetic renal disease (urinary albumin:creatinine ratio > 3 mg/mmol and/or reduced eGFR) OR known cardiovascular disease OR 5 year CVD risk > 15% regardless of their glycaemic control or other glucose lowering therapies. In these patients, GLP1RA are likely preferable to SGLT2i if cerebrovascular disease predominates, but both classes can be used together with additional benefits on reducing glucose levels, weight and cardiovascular disease. Therefore, SGLT2i is typically the best agent to add to GLP1RA, and GLP1RA to SGLT2i if the HbA1c remains above target. This is a mismatch with the Special Authority criteria as only SGLT2i or GLP1RA will be funded as discussed below.
Further evidence is awaited to confirm the role of GLP1RA in primary prevention, but dulaglutide may prevent cardiovascular events in those with multiple risk factors. Regardless, in patients with no renal and cardiovascular disease, GLP1RA are a useful 2nd line agent if required for glycaemic control particularly if weight loss is desirable. Can consider introducing after vildagliptin since vildagliptin in combination with metformin is the only currently known 2nd line agent to delay the need for insulin therapy in type 2 diabetes. But unlike GLP1RA, vildagliptin does not typically lead to weight loss and is a less potent glucose lowering therapy. In these patients, GLP1RA will likely lead to greater improvements in glycaemic control and weight loss than SGLT2i.
Increase glucose-induced insulin secretion and decrease gastric emptying, appetite and glucagon secretion by activating the GLP-1 receptor (GLP1R)
Useful alternative to starting basal insulin
Dulaglutide and liraglutide (Victoza and not Saxenda) are the only available and registered GLP1RA for type 2 diabetes in Aotearoa New Zealand. They are subcutaneous injections (very similar to insulin pens) and are funded under special authority criteria
Special Authority Criteria
Patient has type 2 diabetes with an HbA1c > 53 mmol/mol despite at least 3 months of regular use of metformin and/or an alternative glucose lowering therapy, not on a funded SGLT2i (i.e. empagliflozin) AND any of the following:
Diabetic renal disease (urinary albumin:creatinine ratio > 3 mg/mmol and/or eGFR < 60 mL/min) OR
Known cardiovascular disease (any ischaemic heart disease, cerebrovascular event, peripheral vascular disease, congestive heart failure or familial hypercholesterolaemia) OR
5 year cardiovascular disease risk > 15% OR
A high lifetime cardiovascular risk due to onset of diabetes in childhood or as a young adult OR
Māori or Pacific ethnicity
There is no conclusive data to suggest that either dulaglutide or liraglutide is superior, but dulaglutide is likely the preferred GLP1RA for most patients as it is associated with less adverse effects and unlike liraglutide it is a weekly injection and has been shown to be effective in primary prevention of CV events in high-risk patients. Liraglutide (Victoza) is a useful alternative for those who cannot tolerate dulaglutide 1.5 mg weekly, prefer daily injections, for those treated on doses of ≤ 1.8 mg/day of Liraglutide (Saxenda) for obesity, or if dulaglutide is not available.
NB: There has been widespread fear, misinformation and stockpiling over the worldwide shortage of dulaglutide, but at present there are adequate supplies of dulaglutide in Aotearoa New Zealand to continue best and current practice.PHARMAC will keep this link and Eli Lilly (producers of dulaglutide) will keep this link updated to ensure accurate information of when any shortage of dulaglutide will occur and which patients may be forced to switch from dulaglutide to liraglutide.
If starting dulaglutide then start 1.5 mg weekly as this is the only dose available in Aotearoa New Zealand. NB: Dulaglutide is available in 0.75 mg, 1.5 mg, 3.0 mg and 4.5 mg weekly doses internationally, therefore it is now best practice to consider adding further dulaglutide 1.5 mg injections of per week if tolerating well and the HbA1c remains above target to a maximum of 4.5 mg of dulaglutide per week, given the lack of availability of other doses. Patients funded under the special authority criteria do not need to pay any extra and pharmacies will be fully reimbursed. Patients self-funding dulaglutide will need to pay for the additional number of injections. Additional injections each week may be administered on the same day or spread out over the week e.g. every 3-4 days if on 2 injections of dulaglutide per week.
If starting liraglutide (Victoza) then start 0.6 mg dailyand increase to 1.2 mg daily after 1 week (may delay if significant adverse effects). Doses of liraglutide can be increased to 1.8 mg daily in 2-3 weeks if glucose levels remain elevated or at any stage if the HbA1c remains above target.
NB: Need to prescribe BD 4 or 5 mm needles (these are funded) with liraglutide and ensure sharps disposal as per local guidelines
Liraglutide 1.8 mg daily appears to have a similar glucose lowering potency to dulaglutide 1.5 mg weekly, but is associated with more gastrointestinal adverse effects. Therefore, if forced to switch from dulaglutide to liraglutide - start liraglutide 0.6 mg daily for 1 week, then 1.2 mg daily for 1 week and then to 1.8 mg daily. The rate of titration can be slowed if significant adverse effects or increased if no adverse effects.
When starting GLP1RA:
Provide ongoing support and education for lifestyle management
Metformin should be continued unless contraindicated or not tolerated
Need to stop DPPIV inhibitors (i.e. vildagliptin) as they become redundant
Other glucose lowering therapies should be continued if required for glycaemic control and/or cardiorenal protection (e.g. SGLT2i)
If introduced to a regimen with insulin and/or sulfonylureas, then the dose of insulin and/or sulfonylureas may need to be reduced to prevent hypoglycaemia (particularly if the HbA1c is < 64 mmol/mol). Any reduction is best based on blood glucose levels, but recommended proactive reductions in those with tight glycaemic control include:
15-20% reduction in the dose of total daily insulin. Consider switching premixed insulin or basal plus one insulin regimens to basal insulin alone if HbA1c < 64 mmol/mol.
50% reduction in the doses of sulfonylureas. Consider stopping sulfonylureas for those on ≤ 80 mg of gliclazide per day or ≤ 5 mg of glipizide per day if HbA1c < 64 mmol/mol.
NB: Patients with an HbA1c > 75 mmol/mol with no episodes of hypoglycaemia will typically not require any reduction in insulin and/or sulfonylureas
Warn of the potential adverse effects and reassure that mild symptoms typically resolve despite continuing treatment. Discuss tips to avoid gastrointestinal adverse effects such as eating smaller meals, stopping eating when feeling full, avoiding fatty and spicy foods, not to eat within 2 hours of bed and to remain well hydrated.
Explain that both dulaglutide or liraglutide should be refrigerated for long-term storage, but either agent is fine at temperatures < 30◦C for up to 14 days.
Adverse effects of GLP1RA:
Nausea, vomiting, anorexia and diarrhoea – typically transient and improves on continued treatment
Injection site reactions e.g. nodules – typically transient and improves on continued treatment
Pancreatitis (rare)
Myalgias and muscle weakness (rare)
Stevens-Johnson’s syndrome (rare)
Thrombocytopenia (rare)
Non-funded available GLP1RA in NZ are subcutaneous injections of:
Liraglutide (Saxenda) for treatment of obesity (typically 1.8 mg - 3 mg s/c daily)
Exenatide 5 – 10 μg s/c bd
Exenatide extended release 2 mg s/c weekly (has been withdrawn from NZ market)
The funding/special authority criteria for GLP1RA in New Zealand ensures access for high risk patients, but is not fully consistent with best practice. Although expensive at a minimum of $115 excl. GST per month (dulaglutide currently cheapest), all patients who do not meet the special authority criteria should be offered to self-fund GLP1RA if no contraindications or significant precautions in the following situations:
Patients with diabetic renal disease and/or known cardiovascular disease and/or 5 year CVD risk > 15% with an HbA1c < 53 mmol/mol and/or eGFR 60 - 90 mL/min without microalbuminuria
All patients with diabetic renal disease and/or known cardiovascular disease and/or 5 year CVD risk > 15% on funded SGLT2i (i.e. empagliflozin) therapy
Overweight or obese patients with an HbA1c above target despite regular use or inability to tolerate metformin
All other patients with an HbA1c above target despite regular use or inability to tolerate metformin and vildagliptin
In all patients with an HbA1c to target where a GLP1RA may be preferred to limit adverse effects from thiazolidinedione, sulfonylurea and/or insulin therapy (particularly weight gain and hypoglycaemia)
Pregnancy, breastfeeding or children or youth < 18 years of age*
*NB: Phase III safety data now confirms that dulaglutide and liraglutide are safe and effective in 10 - 17 year olds with type 2 diabetes. Use of GLP1RA in this age group is still awaiting approval from regulatory bodies such as the FDA and Medsafe and so is 'off-label'. But it would now be reasonable to consider using either dulaglutide or liraglutide in all patients with type 2 diabetes > 10 years of age when clinically appropriate. For more information on responsibilities when prescribing for an 'off-label' use please click here .
Not recommended for use in:
Severe gastrointestinal disease including gastroparesis
Previous pancreatitis
Medullary thyroid carcinoma or history of MEN2 syndrome
