Exenatide — clinical evidence

§3Clinical evidence

§3.1Atherosclerotic cardiovascular disease and cardiovascular risk reduction

Anchor outcome. Three-point major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke).

Effect as recorded. MACE hazard ratio 0.91 — non-inferior to placebo but not superior; HR 0.91 (95 % CI 0.83 to 1.00); p = 0.06 for superiority.^[1,2]

Certainty. High certainty The Institute records this as a clear negative superiority result and cautions against class-wide extrapolation of cardiovascular benefit from it.

Contributing trials. EXSCEL. Full structured abstracts are published for each.

Full evidence extract for atherosclerotic cardiovascular disease and cardiovascular risk reduction · Indication assessment

§3.2Type 2 diabetes mellitus

Anchor outcome. Change in HbA1c (%, mmol/mol).

Effect as recorded. −0.8 to −1.9 % HbA1c depending on presentation and background therapy; DURATION-6 difference versus liraglutide +0.21 % (95 % CI 0.08 to 0.33), favouring liraglutide.^[2,3]

Certainty. High certainty Long clinical record; the extended-release presentation is superior to the immediate-release one for HbA1c.

Contributing trials. DURATION-1 · DURATION-6 · AMIGO-1. Full structured abstracts are published for each.

Full evidence extract for type 2 diabetes mellitus · Indication assessment

§3.3Delayed gastric emptying and gastrointestinal motility effects

Anchor outcome. Gastric emptying half-time by scintigraphy or breath test.

Effect as recorded. Marked acute delay in gastric emptying that shows partial tachyphylaxis with continued twice-daily dosing; pharmacodynamic.^[3,4]

Certainty. Moderate certainty The clearest human demonstration of gastric-emptying tachyphylaxis in the class.

Contributing trials. EXENATIDE-GE-PD. Full structured abstracts are published for each.

Full evidence extract for delayed gastric emptying and gastrointestinal motility effects · Indication assessment

§3.4Obesity and overweight in adults

Anchor outcome. Percentage change in body weight from baseline.

Effect as recorded. −2.3 to −3.6 kg; modest.^[4,5]

Certainty. Moderate certainty No obesity indication was pursued.

Contributing trials. DURATION-1. Full structured abstracts are published for each.

Full evidence extract for obesity and overweight in adults · Indication assessment

References cited on this page

References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.

1. Holman RR, Bethel MA, Mentz RJ, Thompson VP, Lokhnygina Y, Buse JB, Chan JC, Choi J, Gustavson SM, Iqbal N, Maggioni AP, Marso SP, Öhman P, Pagidipati NJ, Poulter N, Ramachandran A, Zinman B, Hernandez AF. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine 2017;377(13):1228–1239. doi:10.1056/NEJMoa1612917 · PMID 28910237
2. Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). The Lancet 2009;374(9683):39–47. doi:10.1016/S0140-6736(09)60659-0 · PMID 19515413
3. Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metabolism 2018;27(4):740–756. doi:10.1016/j.cmet.2018.03.001 · PMID 29617641
4. Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes — state-of-the-art. Molecular Metabolism 2021;46:101102. doi:10.1016/j.molmet.2020.101102 · PMID 33068776
5. Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharmaceutical Research 2010;27(4):544–575. doi:10.1007/s11095-009-0045-6 · PMID 20143256

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