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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 likely additional benefits
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To date, there is no convincing evidence that GLP1RA are effective in primary prevention of cardiovascular and/or renal disease. But, 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, but both classes can be used together with likely additional benefits
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Increase glucose-induced insulin secretion and decrease gastric emptying, appetite and glucagon secretion by activating the GLP-1 receptor (GLP1R)
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Useful alternative to starting basal insulin
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All available GLP1RA in New Zealand are subcutaneous injections (very similar to insulin pens)
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Special Authority Criteria
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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:
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Diabetic renal disease (urinary albumin:creatinine ratio > 3 mg/mmol and/or eGFR < 60 mL/min) OR
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Known cardiovascular disease(any ischaemic heart disease, cerebrovascular event, peripheral vascular disease, congestive heart failure or familial hypercholesterolaemia) OR
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5 year cardiovascular disease risk > 15% OR
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A high lifetime cardiovascular risk due to onset of diabetes in childhood or as a young adult OR
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Māori or Pacific ethnicity
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NB: Only the 1.5 mg per week dose of dulaglutide will be available in New Zealand initially
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When starting GLP1RA:
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Provide ongoing support and education for lifestyle management
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Metformin should be continued unless contraindicated or not tolerated
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Need to stop DPPIV inhibitors (i.e. vildagliptin)
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Other glucose lowering therapies should be continued if required for glycaemic control and/or cardiorenal protection (e.g. SGLT2i)
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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 a 15-20% reduction in the dose of total daily insulin and a 50% reduction in the doses of sulfonylureas is a useful starting point in those with tight glycaemic control. Patients with an HbA1c > 75 mmol/mol with no episodes of hypoglycaemia will typically not require any reduction in insulin and/or sulfonylureas
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Warned of the potential adverse effects and reassured that mild symptoms typically resolve despite continuing treatment
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Adverse effects of GLP1RA:
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Nausea, vomiting, anorexia and diarrhoea – typically transient and improves on continued treatment
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Injection site reactions e.g. nodules – typically transient and improves on continued treatment
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Pancreatitis (rare)
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Myalgias and muscle weakness (rare)
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Stevens-Johnson’s syndrome (rare)
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Thrombocytopenia (rare)
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Non-funded available GLP1RA in NZ are subcutaneous injections of:
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Liraglutide 1.8 mg s/c daily (3 mg sc daily if treating obesity)
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Exenatide 5 – 10 μg s/c bd
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Exenatide extended release 2 mg s/c weekly (will shortly be withdrawn from NZ market)
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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 $300 - 500 per month, 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:
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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
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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
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Overweight or obese patients with an HbA1c above target despite regular use or inability to tolerate metformin
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All other patients with an HbA1c above target despite regular use or inability to tolerate metformin and vildagliptin
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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)
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eGFR < 30 mL/min
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Type 1 diabetes
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Not recommended for use in:
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Children or youth (< 18 years), pregnancy and breastfeeding
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Severe gastrointestinal disease including gastroparesis
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Previous pancreatitis
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Medullary thyroid carcinoma or history of MEN2 syndrome