Exenatide is indicated for the treatment of type 2 diabetes mellitus in combination with metformin, sulfonylureas, or metformin and a sulfonylurea in patients who have not achieved adequate glycaemic control. It is a glucagon-like peptide-1 analogue and exhibits a protective effect on beta-cells.

Exenatide controls blood sugar levels by enhancing glucose-dependent insulin secretion and suppressing inappropriately elevated glucagon release. It also slows gastric emptying, thereby reducing the rate at which glucose levels rise after meals. Exenatide may also help with weight loss as it can reduce appetite and increase satiety.

Exenatide is available as a subcutaneous (SC) pre-filled pen injection that can be administered twice daily or once weekly. The once-weekly formulation, Bydureon®, is now on the Pharmaceutical Benefits Scheme (PBS). This makes treatment more affordable for patients and less intrusive as patients will avoid up to 13 injections per week.

Bydureon® should be administered on the same day each week, with or without food. In contrast, Byetta® (immediate release exenatide) needs to be administered twice daily within the one hour before breakfast and dinner (or before two main meals for the day, which should be at least six hours apart). It should not be administered after a meal.

Bydureon® is presented as a 2mg injection that is administered once a week, and no dose titration is required. It can be administered subcutaneously to the thigh, abdomen, or the back of the upper arms. If a dose is missed, the patient should be advised to inject as soon as it is remembered. The next dose should then be administered on the usual injection day as long as it is at least one day after the previous dose. Two injections should not be given on the same day.

Gastrointestinal adverse effects are common and may affect up to 50% of patients. Nausea, vomiting, and diarrhoea usually improve with continued treatment and rarely result in therapy discontinuation. If patients are affected by gastrointestinal adverse effects, they should be counselled to maintain their fluid intake to avoid dehydration. Bydureon® should not be used in patients with severe gastrointestinal disease (e.g. gastroparesis, dumping syndrome) as it delays gastric emptying. Gastrointestinal adverse effects appear to be less pronounced with the once-weekly formulation compared to the twice-daily product. This is due to the more gradual increase in serum exenatide concentrations during dosing with the extended release formulation.

Less common adverse effects include increased heart rate and injection site reactions such as pruritus, erythema, and induration. Hypoglycaemia is rare with monotherapy. However, while there is no increased risk when combined with metformin, there is an increased risk of hypoglycaemia when exenatide is combined with a sulfonylurea or insulin. If a sulfonylurea is used concomitantly, dose adjustment may be required to reduce the risk of hypoglycaemia.

Exenatide has rarely been associated with the development of pancreatitis and should be avoided in patients with a history of this condition. Rare cases of renal adverse effects including acute renal failure and worsening of chronic renal failure have also been reported. Exenatide is, therefore, contraindicated in patients with a creatinine clearance of less than 30ml/min.

Due to the observed delay in gastric emptying, exenatide may reduce the peak levels of oral medications administered at the same time. This effect is less pronounced with the once-weekly formulation, and dose adjustments of oral medications may not be necessary.

Patients treated with exenatide exhibit improved fasting and postprandial blood sugar levels after four weeks of therapy. Lower glycated haemoglobin (HbA1c) levels are achieved after one to three months, demonstrating improved control of average blood sugar levels.

References:

  1. AstraZeneca Pharmaceuticals. Bydureon patient information booklet. Wilmington: AstraZeneca; 2015.
  2. AstraZeneca Pharmaceuticals. Quick reference prescribing guide. Wilmington: AstraZeneca; 2016.
  3. Reutens AT, Shaw JE. Incretin mimetics and enhancers: clinical applications. Aust Prescr. 2008; 31(4): 104-8.
  4. Type 2 diabetes. In: Rossi S, editor. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook; 2016.

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