Exenatide research findings - The Echo Compendium

Exenatide MARKETED

cns-neuropsychiatric Decrease

High evidence

ADDICTION (tobacco) - the smoking RCT: extended-release exenatide added to nicotine patch improved biochemically-confirmed smoking abstinence vs patch alone at 6 weeks...

Yammine L, Green CE, Kosten TR et al., Nicotine Tob Res, 2021 Source

Full findingADDICTION (tobacco) - the smoking RCT: extended-release exenatide added to nicotine patch improved biochemically-confirmed smoking abstinence vs patch alone at 6 weeks and reduced post-cessation weight gain, in prediabetic/overweight smokers.

PopulationYammine pilot RCT: N=84 prediabetic/overweight smokers; double-blind; exenatide 2 mg weekly vs placebo, both with nicotine patch; 6 weeks; CO-confirmed.

Fundingacademic / NIH - UTHealth Center for Clinical and Translational Sciences (NIH CTSA) + PARTNERS Research Awards; no industry sponsor (prior 'AstraZeneca' inference was WRONG)

Scope limitssmall sample (N~84)

Comparatorsplacebo (with nicotine patch in both arms)

Exenatide MARKETED

cns-neuropsychiatric Decrease

Moderate evidence

NEURODEGENERATION (Parkinson's) - the positive phase-2: in a single-centre phase-2 trial in moderate Parkinson's, exenatide improved off-medication motor scores vs...

Athauda D, Maclagan K, Skene SS et al., Lancet, 2017 Source

Full findingNEURODEGENERATION (Parkinson's) - the positive phase-2: in a single-centre phase-2 trial in moderate Parkinson's, exenatide improved off-medication motor scores vs placebo at 60 weeks; the authors could not distinguish disease modification from a long-lasting symptomatic effect. The result that drove a decade of GLP-1-in-PD optimism.

PopulationAthauda phase-2 (NCT01971242): N=62 moderate idiopathic PD; single-centre double-blind RCT; exenatide 2 mg weekly, 48 weeks + 12-week washout.

Fundingacademic / philanthropic - Michael J Fox Foundation for Parkinson's Research (not AstraZeneca)

Scope limitssingle-centre/referral-enriched; small sample (N~62)

Comparatorsplacebo

Exenatide MARKETED

cns-neuropsychiatric No change

Moderate evidence

NEURODEGENERATION (Parkinson's) - THE LOAD-BEARING NEGATIVE: the definitive multicentre phase-3 trial found that once-weekly exenatide did NOT slow Parkinson's...

Vijiaratnam N, Girges C, Auld G et al., Lancet, 2025 Source

Full findingNEURODEGENERATION (Parkinson's) - THE LOAD-BEARING NEGATIVE: the definitive multicentre phase-3 trial found that once-weekly exenatide did NOT slow Parkinson's progression. The authors concluded there is no evidence to support exenatide as disease-modifying. This OVERTURNS the positive phase-2.

PopulationVijiaratnam/Foltynie phase-3 (NCT04232969): N=194 PD; six UK hospitals; double-blind RCT; extended-release exenatide 2 mg weekly, 96 weeks.

Fundingacademic-NIHR + charity-Cure Parkinson's (NOT AstraZeneca)

Scope limitssmall sample (N~194)

Comparatorsplacebo

Exenatide MARKETED

cns-neuropsychiatric Mixed

Low evidence

ADDICTION (alcohol) - the counter-pole RCT: in treatment-seeking AUD patients, once-weekly exenatide added to CBT did NOT significantly reduce heavy drinking days...

Klausen MK, Jensen ME, Moller M et al., JCI Insight, 2022 Source

Full findingADDICTION (alcohol) - the counter-pole RCT: in treatment-seeking AUD patients, once-weekly exenatide added to CBT did NOT significantly reduce heavy drinking days (primary endpoint NEGATIVE), but attenuated fMRI alcohol-cue reactivity in the ventral striatum and lowered dopamine-transporter availability, with an exploratory benefit in the obese subgroup. The cleaner test of real-world drinking, and it failed its primary.

PopulationKlausen AUD RCT (NCT03232112): N=127 treatment-seeking AUD; double-blind placebo-controlled; exenatide 2 mg weekly + CBT, 26 weeks; Denmark.

Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)

Scope limitssmall sample (N~127)

Comparatorsplacebo

Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.

Exenatide MARKETED

Insulin and beta-cell function Increase

Moderate evidence

The canonical washout test of DURABILITY (reversible pole): one year of exenatide improved clamp-measured beta-cell function markedly versus titrated glargine at...

Bunck MC, Diamant M, Corner A et al., Diabetes Care, 2009 Source

Full findingThe canonical washout test of DURABILITY (reversible pole): one year of exenatide improved clamp-measured beta-cell function markedly versus titrated glargine at matched glycaemia, but after a 4-week off-drug washout the beta-cell-function measures returned to pretreatment in both arms - the authors concluded ongoing treatment is necessary, i.e. the 1-year on-treatment gain is NOT a durable, disease-modifying change.

PopulationBunck et al.: metformin-treated T2D, N=69 (exenatide 36 / glargine 33), 52 wk + 4-wk off-drug, open-label RCT.

Fundingindustry-Amylin Pharmaceuticals/Eli Lilly

Scope limitsopen-label (unblinded); small sample (N~69)

Comparatorsinsulin glargine

Exenatide MARKETED

Insulin and beta-cell function Increase

Moderate evidence

The contested PRESERVATION pole, recorded beside its own contradiction: in the 3-year extension, the off-drug disposition index was sustained ABOVE pretreatment with...

Bunck MC, Corner A, Eliasson B et al., Diabetes Care, 2011 Source

Full findingThe contested PRESERVATION pole, recorded beside its own contradiction: in the 3-year extension, the off-drug disposition index was sustained ABOVE pretreatment with exenatide (and fell with glargine), which the authors read as a beneficial effect on beta-cell health - standing AGAINST the same group's 1-year result where the off-drug measures reverted. Duration of exposure and the disposition-index (vs raw secretion) endpoint may drive the divergence.

PopulationBunck et al. 3-year extension: metformin-treated T2D, N=36 completers (exenatide 16 / glargine 20), measured 4 wk after discontinuation, open-label RCT extension.

Fundingindustry-Amylin Pharmaceuticals and Eli Lilly

Scope limitsopen-label (unblinded); post-hoc (not prespecified); small sample (N~36); surrogate/exploratory endpoint

Comparatorsinsulin glargine

Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.

Exenatide MARKETED

Cardiovascular outcomes No change

High evidence

In T2D (most with prior CVD), once-weekly exenatide was non-inferior to placebo for MACE; superiority was not met (HR favoured exenatide, CI crossed 1).

Holman RR et al., N Engl J Med, 2017 Source

PopulationEXSCEL: N=14,752; T2D, ~73% with prior CVD; double-blind placebo-controlled pragmatic RCT; median 3.2 years.

Fundingindustry-Amylin Pharmaceuticals (AstraZeneca subsidiary)

Scope limitsADDED (not in prior rows). Largest GLP-1 CVOT; non-inferior with a near-miss on superiority (P=0.06). Sits between the neutral (ELIXA) and superior (LEADER/SUSTAIN-6/REWIND) trials. Exendin-4-based, yet the class meta found no heterogeneity by structural homology.

Comparatorsplacebo

Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.

Exenatide MARKETED

Glycaemic control Decrease

Moderate evidence

Exenatide ER 2 mg once weekly reduced HbA1c by approx -1.9% vs -1.5% for exenatide IR 10 mcg twice daily at 30 weeks; weight loss approx -3.6 kg with either...

Drucker DJ et al., Lancet 2008 (DURATION-1) Source

Full findingExenatide ER 2 mg once weekly reduced HbA1c by approx -1.9% vs -1.5% for exenatide IR 10 mcg twice daily at 30 weeks; weight loss approx -3.6 kg with either formulation.

PopulationDURATION-1: 295 patients with T2D on background therapy, exenatide ER 2 mg weekly vs IR 10 mcg twice daily, 30-week controlled phase, open-label non-inferiority

Fundingindustry - Amylin Pharmaceuticals / Eli Lilly (disclosed)

Scope limitsopen-label (unblinded)

Comparatorsexenatide IR (twice daily)