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GLP-1 mimetics and analogues

Exenatide and liraglutide are injected drugs that also act on the in-
cretin system. Instead of impeding the degradation of native GLP-1
like DPP-4 inhibitors, exenatide mimics GLP-1, whereas as liraglutide is
an analogue of this incretin. Both of these agents offer considerable
reductions in blood glucose levels and body weight (see Chapter 4).
In addition, exenatide has been shown to have favourable effects on
lipidaemia. The drawbacks of GLP-1 mimetics/analogues include
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their need to be injected, gastrointestinal side effects and a potential
link with acute pancreatitis. Table 4 presents a ‘SWOT’ analysis of these
agents.

Table 4. GLP-1 mimetics/analogues – Strengths, Weaknesses, Opportunities and Threats.

Strengths Weaknesses

z Supplement endogenous GLP-1 and enhance z Long-term data lacking
glucose-dependent insulin secretion
z Should not be used in severe renal impairment or
z Associated with a low incidence of hypoglycaemia end stage renal disease (exenatide)
z Weight loss z Should be used with caution in renal impairment
(liraglutide)
z Significant body of data supporting their use in
T2DM z Price
z Shown to be effective in mono- and combination z Need to be injected
therapy
z Gastrointestinal side effects
z Generally well tolerated
z Not specifically included in all guidelines
z Considerable improvements in lipidaemia (exenatide)
Opportunities Threats

z May confer some degree of cardio-protection z May cause pancreatitis
z Effect of weight loss on CV risk factors z Negative data from CV outcome studies
z T2DM management is moving beyond simple z New compounds with novel modes of action
glycaemic parameters
z The position of many OADs is being eroded by
safety concerns (e.g. SUs, TZDs)
z Patient-centric treatment is increasingly important
z Positive data from CV outcome studies

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