EXENATIDE
Pharmacology
Exenatide is a synthetic form of naturally occurring peptide Exendin-4 in Gila monster 16. It has 50% of sequence homology with native GLP-1 with the substitution of amino acid Arg with Gly at 2nd position, which provides resistance against DPP-4 and a half life of ~2-4hr. It is administered 60min before breakfast and dinner, with a predominant effect of reduction in PPG (Postprandial glucose) 17. Exenatide is rapidly absorbed following subcutaneous administration and eliminated through kidneys after proteolytic degradation by dipeptidyl peptidase IV.18
Clinical Pharmacology
The efficacy and safety of exenatide (5µg and 10µg) administered in patients with T2DM has been assessed in a series of 30-week clinical studies called AMIGO (AC2993 Diabetes Management for Improving Glucose Outcomes).19
AMIGO were triple blind, placebo-controlled studies where more no. of patients treated
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It has C-16 fatty acid (palmitoyl acid) attached via glutamine spacer to lysine at position 26, and substitution of lysine with arginine at position 34 23. Palmitoyl acid binds reversibly to plasma albumin that prevents its degradation by DPP-4 and depot formation at the injection site with slow dissolution is responsible for its prolonged duration of action 24.
Clinical Pharmacology
The Liraglutide Effect and Action in Diabetes (LEAD) program was conducted to investigate the safety and efficacy of liraglutide in patients with T2DM inadequately controlled with lifestyle modifications or oral antidiabetic drugs (OADs). The LEAD study comprised six randomized, Phase 3 clinical studies including 4456 participants across 40 countries. This includes LEAD-3 (Liraglutide as monotherapy), LEAD-2 and LEAD-1(Liraglutide in combination with one OAD) and LEAD-4 and LEAD-5 (Liraglutide in combination with two OADs) and a Head to Head trial with exenatide BID