• GLP1RA are a preferred 2nd line agent in cardiovascular and renal disease as these reduce 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 increased CVD risk >10% 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 unless there is heart failure.

• 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.

• GLP1RA 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 1.5mg weekly SC (Trulicity) and liraglutide 1.8mg od (Victoza) are the only available and registered GLP1RA for type 2 diabetes in Aotearoa New Zealand.  Trulicity is available as a disposable autoinjector, while Victoza is available as a daily dose-titratable pen, and are funded under special authority criteria

• There is no conclusive data to suggest that either dulaglutide or liraglutide is superior, but dulaglutide is likely the preferred GLP1RA for most patients 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, or if dulaglutide is not available.

• 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 daily and 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 for the indication of weight loss are:
  • Semaglutide (Wegovy) and the dual GLP1/GIP RA, Tirzepatide (Mounjaro).  Both will also provide glucose lowering benefits to a greater extent than funded GLP1RA Dulaglutide or Liraglutide.

• Indication
  • Body Mass Index (BMI) ≥30 kg/m2, or ≥27 kg/m2 if they have weight-related health conditions.

• Semaglutide (Wegovy) is also indicated as an adjunct to standard of care therapy to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in adults with established cardiovascular disease, with a Body Mass Index (BMI) ≥ 27 kg/m2.

• Semaglutide (Wegovy) is also approved for the indication of metabolic-associated steatohepatitis (MASH) in adults with moderate to advanced fibrosis.

• Tirzepatide (Mounjaro) is also indicated for obstructive sleep

• Which GLP1RA for weight loss?

• Dulaglutide (funded for those with T2DM) produces a mean weight loss of 5%,

• Semaglutide 2.4mg weekly (self-funded $475 per month) can expect mean 1 year weight loss of 10%

• Tirzepatide 15mg weekly (self-funded $875 per month at maximal dose) can expect mean 1 year weight loss of 13%.   Tirzepatide 5mg ow (cost $500 per month) produces comparable weight loss to Semaglutide 2.4mg ow (cost $475 per month).

• If starting Semaglutide (Wegovy) then start 0.25 mg pen which contains 4 doses for weekly administration, then after 4 weeks, increase to 0.5mg pen which contains 4 doses for weekly administration, then increase to 1mg for 4 weeks then 1.7mg for 4 weeks, then continue at 2.4mg weekly (cost of $475 per month).
  • NB: Need to prescribe BD 4 or 5 mm needles (these are not funded) and ensure sharps disposal as per local guidelines.

• If starting Tirzepatide (Mounjaro) then start 2.5mg pen which contains 4 doses for weekly administration, then after 4 weeks, increase to 5mg pen, then after weeks increase to 7.5mg pen, then to 10mg, then 12.5mg then to 15mg once weekly to continue (cost of $875 for top two doses).  May stop at the last tolerated dose.
  • NB: Need to prescribe BD 4 or 5 mm needles (these are not funded) and ensure sharps disposal as per local guidelines
  • Semaglutide 2.4mg ow (cost $475 per month) produces similar weight loss as Tirzepatide 5mg ow (cost $500 per month), and the latter requires less time to titrate up (4 weeks vs 16 weeks).

The funding/special authority criteria for GLP1RA in New Zealand ensures access to GLP1RA after Metformin, empagliflozin and Vildagliptin if target HbA1c is not achieved or if not tolerant/clinically inappropriate, but is not fully consistent with best practice. There will still be a group of people who will not qualify for funding but will benefit clinically. They can consider self-funding. 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 > 10% with an HbA1c < 53 mmol/mol

• All patients with diabetic renal disease and/or known cardiovascular disease and/or 5 year CVD risk > 10% on funded SGLT2i (i.e. empagliflozin) therapy

• Overweight or obese patients with an HbA1c above target

• 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)

Need to stop in GI illness as per sick day management plan

Not registered for use:

• eGFR < 15 mL/min
• Type 1 diabetes
• Pregnancy, breastfeeding or children < 10 years of age
• 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
• Caution if concerns of malnourishment and/or underweight
• Non-arteritic anterior ischaemic optic neuropathy (NAION)