Dulaglutide (Trulicity®) is a new glucagon-like peptide-1 (GLP-1) analogue available on the Pharmaceutical Benefits Scheme (PBS) for the treatment of type 2 diabetes. GLP-1 is an intestinally-derived incretin hormone that is key in the regulation of blood glucose and satiety.

This insulinotropic peptide is unsuitable as a therapeutic agent as it is rapidly degraded by endogenous enzymes, resulting in a half-life of around two minutes. However, GLP-1 analogues such as liraglutide (Victoza®) and exenatide (Byetta®) have prolonged biological activity and can be administered daily or twice daily respectively. Exenatide is also presented as an extended-release microsphere formulation (Bydureon®) for weekly administration.

Dulaglutide can also be administered weekly, although this is a function of its structure rather than the formulation. The GLP-1 analogue component of dulaglutide is covalently linked to a modified human immunoglobulin fragment. This increases resistance to enzymatic degradation, while the larger size slows absorption and reduces renal clearance.

Head-to-head trials of GLP-1 analogues demonstrate a reduction in HbA1c of between 3mmol/mol (0.3%) and 21mmol/mol (1.9%). However, differences in study design and patient cohorts make it difficult to directly compare the efficacy of these agents. Some studies suggest that liraglutide produces a greater reduction in HbA1c compared to exenatide and a similar reduction compared to dulaglutide.

Gastrointestinal adverse effects such as nausea, vomiting, diarrhoea, and dyspepsia are commonly reported with this class. Modest weight loss may also occur, which can be beneficial in patients who are overweight or obese. The risk of hypoglycaemia is low with monotherapy as the action of these agents is glucose-dependent. Dose adjustments may be required for concomitant sulfonylurea or insulin therapy.

References:

  1. Lee S, Lee DY. Glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes. Ann Pediatr Endocrinol Metab. 2017; 22(1): 15-26.
  2. Madsbad S. Review of head‐to‐head comparisons of glucagon‐like peptide‐1 receptor agonists. Diabetes Obes Metab. 2016; 18(4): 317-32.
  3. Trulicity®(dulaglutide rch) Australian approved product information. West Ryde: Eli Lilly. Approved October 2017.

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