Page 68 - 51 the significance--29.2_opt

reduced HbA by -0.4% to -0.86% and body weight by 1.6kg to 2.8kg de-
1C
pending on the dose and the study. 96-98 A study has shown that liraglutide
is superior to sitagliptin in terms of HbA reduction (-1.5% vs. -0.9%). In a
99
1c
head-to-head study, liraglutide also out-performed exenatide; reducing
HbA by -1.12% compared with -0.79% for exenatide. 100
1c
With increasing interaction of GLP-1 or GLP-1 receptor agonists with
GLP-1 receptors, as obtained with both GLP-1 analogues (high, phar-
macological concentrations) and DPP-4 inhibitors (near-physiological
concentrations, approximately 2-3 fold above placebo levels), there
are significant effects on the pancreatic islets and the respective glu-
cose homeostasis. Higher concentrations (which may not be reached
with DPP-4 inhibitor therapy due to their mechanism of action) are
needed to slow down gastric emptying and to reduce appetite – char-
acteristics of exenatide and liraglutide. Significant weight loss is one of
the major advantages of GLP-1 mimetic/analogue therapy.
Safety and tolerability

In terms of safety tolerability, exenatide and liraglutide appear to be
generally well tolerated, although they are associated with gastro-
intestinal adverse events, such as nausea, diarrhoea and vomiting. 101 Both,
exenatide and liraglutide have been shown to be associated with im-
proved cardiovascular disease risk factors. 102 103 Exenatide should not
be used in patients with severe renal impairment or end-stage renal dis-
ease and should be used with caution in patients with renal transplan-
tation. Liraglutide should be used with caution in renal impairment due
94
to limited experience in this patient population. Acute pancreatitis is
95
a potential concern for all incretin-based therapies. There have been
reports of acute pancreatitis in people treated with exenatide. Albeit
rare, these prompted the regulatory bodies to release safety warnings
regarding the use of this drug. It seems that acute pancreatitis is not
94
limited to the GLP-1 mimetics. As of January 2010 88 cases of acute
pancreatitis in patients taking sitagliptin had been reported to the FDA,
prompting a revision of the package insert for this drug as well. The
104
recent analysis of the FDA adverse events reporting database concludes
that careful long-term monitoring of patients treated with GLP-1 mim-
etics or DPP-4 inhibitors is required. 80

Linagliptin – key characteristics

Linagliptin is a forthcoming addition to the DPP-4 inhibitor class. This sec-
tion looks at the key attributes of this drug, especially those that differ-
entiate it from the other DPP-4 inhibitors.

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