Table 1 Characteristics of GLP-1RAs
Drug | Structure/homology To Human GLP-1 | DPP-4 cleavage | Half-life | Recommendations in renal impairment | Antibodies |
|---|---|---|---|---|---|
Substitution of alanine in position 2 by glycine 53% homology | Resistant | 2–4 h (12 h for sustained release exenatide) | Not recommended in patients with GFR < 30 mL/min Sustained release exenatide is only licensed in mild-to-moderate renal impairment (GFR > 50 mL/min) | Anti-drug antibodies were more common, and titres were higher with exenatide once weekly than with exenatide twice daily | |
Exendin-4 elongated with a residue of 6 lysines attached to the C-terminus 50% homology | Resistant | 2–3 h | Not recommended in patients with a GFR < 30 mL/min | 56–60% of patients developed anti-drug antibodies, with no apparent effect on efficacy or safety | |
One amino acid substitution (Lys34Arg) with the addition of a C-16 acyl group (palmitoyl) attached to Lys26 via a glutamate linker 97% homology | Resistant | 10–12 h | No restrictions or dose adjustments required | Low incidence of anti-drug antibodies | |
Composed of a GLP-1 (7–36) dimer fused to recombinant human albumin 95% homology | Resistant | 5 days | No restrictions or dose adjustments required | Low incidence of anti-drug antibodies | |
Two DPP-4 resistant GLP-1 molecules covalently bound to a modified immunoglobulin 4 Fc fragment 90% homology | Resistant | 5 days | No restrictions or dose adjustments required | Low incidence of anti-drug antibodies | |
Alpha-aminoisobutyric acid substitution at positions 8 and 35 of the human GLP-1(7–36)NH2 that enhances enzymatic stability and potency 93% homology | Resistant | 165 h | Renal impairment alters the pharmacokinetics of taspoglutide. The degree of renal impairment was associated with an increased exposure to taspoglutide and an increased risk of gastrointestinal adverse events | Incidence of anti-drug antibodies as high as 49% | |
Acyl group with a steric diacid at Lys26 and a large synthetic spacer and modified by the presence of a alpha-aminobutyric acid in position 8 94% homology | Resistant | 1 week | No restrictions or dose adjustments required for patients with renal impairment | Low incidence of anti-drug antibodies |