32 findings across 17 drug records. Domain pages are descriptive indexes, not advice.
Most represented records
Retatrutide (5)
Semaglutide (5)
Liraglutide (4)
GLP-1 RA class (3)
Tirzepatide (2)
Evidence spread
High evidence 1Moderate evidence 16Low evidence 8Very low evidence 7
GLP-1 RA classMARKETED
Appetite and food intakeDecrease
Low evidence
FOLK-CLAIM VERDICT ('these drugs silence food noise'): MIXED. The craving/appetite-reduction CORE is TRUE and instrument-measured (real, not placebo or weight-loss...
SourceDhurandhar EJ et al. Defining and measuring food noise (RAID-FN / FNQ). Nutr Diabetes 202...Source
Full findingFOLK-CLAIM VERDICT ('these drugs silence food noise'): MIXED. The craving/appetite-reduction CORE is TRUE and instrument-measured (real, not placebo or weight-loss halo). BUT (1) 'food noise' as a distinct intrusive-rumination construct was only defined and given instruments in 2025 and has NEVER been a pre-registered trial endpoint - the trials measured cravings/appetite, which overlap but are not identical; (2) 'valued above the weight loss itself' rests entirely on surveys/anecdote - UNPROVEN; (3) drug-specificity is lopsided - robust for semaglutide, mechanistically strong for tirzepatide, THIN and indirect for retatrutide.
PopulationNarrative cross-agent verdict over the craving/appetite evidence (CoEQ/FCI/VAS RCTs; tirz fMRI; reta early/indirect data) + the 2025 food-noise construct literature.
Fundingacademic (Dhurandhar et al.; food-noise construct/measurement paper)
Scope limitssurrogate/exploratory endpoint
Comparatorsplacebo
RetatrutideINVESTIGATIONAL
Appetite and food intakeDecrease
Moderate evidence
Retatrutide's ONLY appetite/eating-behaviour data is a prespecified exploratory analysis in T2D (appetite VAS + Eating Inventory) showing reduced appetite, hunger and...
SourceKanu C et al., Diabetes Obes Metab 2025;27(12):6988-6998Source
Full findingRetatrutide's ONLY appetite/eating-behaviour data is a prespecified exploratory analysis in T2D (appetite VAS + Eating Inventory) showing reduced appetite, hunger and disinhibition; it has NO craving-specific instrument, NO neuroimaging, and its pivotal obesity trial measured no craving at all. So retatrutide 'food noise' reduction is INFERRED by class analogy, NOT demonstrated.
PopulationPrespecified exploratory analysis of the retatrutide phase-2 T2D trial (n=275, 36 wk); reta 0.5-12 mg vs placebo and dulaglutide 1.5 mg.
Fundingindustry-Eli Lilly
Scope limitsnot multiplicity-controlled; small sample (N~275); surrogate/exploratory endpoint
Comparatorsplacebo; dulaglutide 1.5 mg
RetatrutideINVESTIGATIONAL
Appetite and food intakeNot directional
Very low evidence
FOLK-CLAIM VERDICT ('appetite/food noise comes ROARING BACK on retatrutide, on treatment'): UNPROVEN. The self-report SIGNAL is real (a striking, oft-repeated...
SourceSelf-Reported Side Effects Among Reddit Users Taking Unapproved Retatrutide. medRxiv 2026...Source
Full findingFOLK-CLAIM VERDICT ('appetite/food noise comes ROARING BACK on retatrutide, on treatment'): UNPROVEN. The self-report SIGNAL is real (a striking, oft-repeated observation), but the causal claim is unsupported: (1) the only source is a non-peer-reviewed Reddit text-mining preprint of an unregulated grey-market population (selection/recall/dosing-error/contamination bias); (2) no controlled trial shows paradoxical on-treatment increased appetite; (3) the proposed 'glucagon' mechanism is BACKWARDS - glucagon-receptor agonism SUPPRESSES appetite. Plausibly explained by inconsistent grey-market dosing, normal physiological hunger as the body nears a new set-point, or reporting artefact. NOTE: distinct from the REAL post-discontinuation appetite rebound (D4).
PopulationNon-peer-reviewed medRxiv Reddit text-mining preprint (grey-market reta users); contrasted with the reta phase-2 trial AE profile.
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsno outcome data yet (ongoing)
SemaglutideMARKETED
Appetite and food intakeDecrease
High evidence
Semaglutide 2.4 mg reduces food cravings and improves control of eating on the VALIDATED Control of Eating Questionnaire, with improvements sustained to 2 years - the...
SourceWharton S et al. Two-year effect of semaglutide 2.4 mg on control of eating (STEP 5 CoEQ)...Source
Full findingSemaglutide 2.4 mg reduces food cravings and improves control of eating on the VALIDATED Control of Eating Questionnaire, with improvements sustained to 2 years - the instrument-grade evidence underlying the lay 'food noise' claim for semaglutide.
PopulationSTEP-5 CoEQ subgroup (n=174, 104 wk) + mechanism-of-action RCT (n=72, 20 wk); adults with overweight/obesity; semaglutide 2.4 mg vs placebo.
Fundingindustry - Novo Nordisk
Scope limitssmall sample (N~174)
Comparatorsplacebo
TirzepatideMARKETED
Appetite and food intakeDecrease
Moderate evidence
Tirzepatide reduces food cravings (Food Craving Inventory) and food-cue reward-circuit reactivity (fMRI) - the strongest MECHANISTIC evidence for the lay 'food noise'...
SourceMartin CK, Coskun T et al. Tirzepatide effects on ingestive behaviour and brain response ...Source
Full findingTirzepatide reduces food cravings (Food Craving Inventory) and food-cue reward-circuit reactivity (fMRI) - the strongest MECHANISTIC evidence for the lay 'food noise' claim, demonstrating a central reward component, though the fMRI effect was partial (high-fat/high-sugar regions, not overall palatable-food response).
PopulationPhase-1 ingestive-behaviour RCT (n=114, 6 wk) + a phase-1 RCT FCI secondary analysis (n=55, 18 wk); adults with obesity; tirzepatide vs placebo (+ liraglutide arm).
Fundingindustry-Eli Lilly
Scope limitsconference/abstract-level; small sample (N~114)
Comparatorsplacebo; liraglutide
CagrilintideMARKETED
Appetite and food intakeDecrease
Moderate evidence
Once-weekly cagrilintide (0.3-4.5 mg, 26 wk) produced dose-dependent weight loss greater than placebo and greater than liraglutide 3.0 mg at the top dose in adults...
SourceLau DCW et al. Lancet 2021;398:2160-2172Source
Full findingOnce-weekly cagrilintide (0.3-4.5 mg, 26 wk) produced dose-dependent weight loss greater than placebo and greater than liraglutide 3.0 mg at the top dose in adults with overweight/obesity without diabetes; amylin's mechanism is satiety induction via homeostatic and hedonic brain regions. Ad libitum energy intake was not the trial endpoint; weight loss is the downstream integral.
PopulationAdults with overweight/obesity without diabetes, n=706 cagrilintide, 26 weeks (NCT03856047)
Fundingindustry - Novo Nordisk
Scope limitsSponsor (Novo Nordisk); COI-flag. Newly added. Weight-as-proxy for appetite; no direct VAS/ad-libitum-intake endpoint. Amylin satiety mechanism per class. GI AEs (nausea 20-47% vs 18% placebo).
Comparatorsplacebo; liraglutide 3.0 mg
CagrilintideMARKETED
Appetite and food intakeDecrease
Very low evidence
A cross-species (rat/mouse/macaque/human) dorsal vagal complex atlas defined amylin-receptor (Calcr) neuronal mediators of cagrilintide's energy-balance effects:...
SourceLudwig MQ et al., Nat Metab 2026 (advance online)Source
Full findingA cross-species (rat/mouse/macaque/human) dorsal vagal complex atlas defined amylin-receptor (Calcr) neuronal mediators of cagrilintide's energy-balance effects: long-term cagrilintide upregulates prolactin-releasing hormone (Prlh) in conserved NTS Calcr/Prlh cells, and knocking down DVC Prlh abrogates cagrilintide's (but not semaglutide's) effect on food intake/body weight in rats — a mechanistic substrate for amylin-driven intake suppression.
PopulationRat (primary functional), with mouse/macaque/human transcriptomic mapping
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsanimal data; human relevance uncertain
Co-infusion of individually subanorectic doses of GLP-1 and glucagon in humans reduced food intake ~13% and raised energy expenditure ~53 kcal/day while protecting...
SourceCegla J et al., Diabetes 2014;63(11):3711-3720Source
Full findingCo-infusion of individually subanorectic doses of GLP-1 and glucagon in humans reduced food intake ~13% and raised energy expenditure ~53 kcal/day while protecting against glucagon-induced hyperglycaemia. Combination (GCGR+GLP-1R) intake datum — the glucagon-arm contribution cannot be isolated; subanorectic glucagon by design contributes little alone (intake reduction most plausibly GLP-1-led).
CNS-GIPR signalling regulates body weight and food intake: HFD-fed CNS-Gipr-KO and humanised-GIPR mice with CNS-hGIPR deletion show decreased body weight, and acute...
SourceZhang Q et al., Cell Metab 2021;33(4):833-844.e5Source
Full findingCNS-GIPR signalling regulates body weight and food intake: HFD-fed CNS-Gipr-KO and humanised-GIPR mice with CNS-hGIPR deletion show decreased body weight, and acute central/peripheral acyl-GIP raises cFos in hypothalamic feeding centres coinciding with decreased food intake; the GLP-1/GIP co-agonist intake advantage is extinguished in CNS-Gipr-KO. This is the CNS-GIP appetite-suppression pole.
PopulationMice (genetic + acyl-GIP)
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsReused from corpus T9-GIPR-01. AGONISM pole of the GIP agonism-vs-antagonism appetite paradox. Mouse — does not license a human CNS-GIP-appetite attribution.
Comparatorsvehicle; GLP-1/GIP co-agonist
GIP (native; Isoglycaemic Clamp Infusion)MARKETED
Appetite and food intakeNo change
Moderate evidence
In a randomised crossover isoglycaemic-clamp study in 17 overweight/obese men, GIP infusion ALONE did not reduce ad libitum energy intake vs saline, whereas GLP-1...
SourceBergmann NC et al., Diabetologia 2019;62(4):665-675Source
Full findingIn a randomised crossover isoglycaemic-clamp study in 17 overweight/obese men, GIP infusion ALONE did not reduce ad libitum energy intake vs saline, whereas GLP-1 alone did; adding GIP did not potentiate GLP-1, and intake on GIP+GLP-1 was significantly HIGHER than on GLP-1 alone — acute human GIP attenuated rather than aided GLP-1's intake suppression.
Fundingacademic - Innovation Fund Denmark and the Vissing Foundation
Scope limitssmall sample (N~17)
Comparatorssaline; GLP-1; GIP+GLP-1
LY3537021MARKETED
Appetite and food intakeDecrease
Low evidence
The selective GIPR agonist LY3537021 produced dose-dependent weight loss in phase 1 whose apparent mode of action is appetite suppression, inferred from spontaneous...
SourceLong-acting GIPR agonist LY3537021 reduces body weight and fasting glucose in T2D: precli...Source
Full findingThe selective GIPR agonist LY3537021 produced dose-dependent weight loss in phase 1 whose apparent mode of action is appetite suppression, inferred from spontaneous adverse events of decreased appetite/early satiety; the formal appetite VAS showed no conclusive effect and energy intake was not formally measured.
PopulationPhase 1 (incl. T2D MAD), humans
Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)
Scope limitsSponsor-authored (all-Lilly); COI-flag. Reused from corpus T9-GIPR-03. Only selective-GIPR-agonist human appetite readout; mechanism INFERRED from AEs, VAS inconclusive (not measured-positive).
Comparatorsplacebo
GLP-1 RA classMARKETED
Appetite and food intakeDecrease
Low evidence
GIPR agonism-versus-antagonism paradox: both GIPR agonism (within tirzepatide) and GIPR antagonism (anti-GIPR antibody within maridebart cafraglutide/MariTide) produce...
SourceDouros JD, Mowery SA, Knerr PJ, J Clin Med 2025;14(11):3812Source
Full findingGIPR agonism-versus-antagonism paradox: both GIPR agonism (within tirzepatide) and GIPR antagonism (anti-GIPR antibody within maridebart cafraglutide/MariTide) produce additive weight loss when combined with GLP-1R agonism; reconciling hypotheses (incretin-crosstalk disinhibition; chronic-agonism desensitisation to functional antagonism; distinct CNS populations) remain genuinely unresolved.
PopulationReview of human/preclinical/genetic evidence
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsCOI-visibility (Indiana Biosciences, ex-Lilly/Novo lineage). Reused from corpus T9-GIPR-04/L1-015. HEADLINE DISCREPANCY held open — both poles recorded, NOT resolved by preference.
Pharmacological GLP-1R blockade with exendin(9-39) only slightly modulated appetite during ad libitum eating and did NOT change food intake, fluid intake or meal...
SourceSteinert RE et al., Am J Clin Nutr 2014;100(2):514-523Source
Full findingPharmacological GLP-1R blockade with exendin(9-39) only slightly modulated appetite during ad libitum eating and did NOT change food intake, fluid intake or meal duration in healthy men, suggesting endogenous GLP-1 is a comparatively weak physiological satiation signal — distinct from the large effect of pharmacological agonism.
PopulationHealthy men, n=10 x2 studies
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitssmall sample (N~10)
Comparatorssaline/vehicle
Glucagon (native, Prandial Infusion)MARKETED
Appetite and food intakeDecrease
Moderate evidence
In normal-weight men, intravenous pancreatic glucagon (~3 ng/kg/min, from 5 min before lunch) significantly reduced test-meal size without detectable side effects; a...
SourceGeary N, Kissileff HR, Pi-Sunyer FX, Hinton V, Am J Physiol 1992;262(6 Pt 2):R975-980Source
Full findingIn normal-weight men, intravenous pancreatic glucagon (~3 ng/kg/min, from 5 min before lunch) significantly reduced test-meal size without detectable side effects; a lower dose (~1.5 ng/kg/min) had no effect, and glucagon+CCK-8 produced an infra-additive intake reduction. Canonical human glucagon-satiety datum.
PopulationNormal-weight young men (small n)
Fundingacademic-NIH/NIDDK
Scope limitsconference/abstract-level
Comparatorssaline; CCK-8
Glucagon (endogenous Blockade)MARKETED
Appetite and food intakeIncrease
Very low evidence
Hepatic-portal infusion of glucagon antibodies during spontaneous meals increased meal size in ad libitum-fed rats, indicating endogenous prandial glucagon contributes...
SourceLe Sauter J, Noh U, Geary N, Am J Physiol 1991;261(1 Pt 2):R162-165Source
Full findingHepatic-portal infusion of glucagon antibodies during spontaneous meals increased meal size in ad libitum-fed rats, indicating endogenous prandial glucagon contributes physiologically to meal termination; the satiety action is relayed by the hepatic vagus (abolished by hepatic vagotomy in companion work).
PopulationAd libitum-fed rats
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsReused from corpus T9-GCGR-04 (mechanism anchor T9-GCGR-03, Geary 1993 PMID:8430871). Loss-of-function leg of the GCGR-satiety case. Human hepatic-vagal pathway not directly demonstrated.
Comparatorscontrol antibody/vehicle
GLP-1 RA classMARKETED
Appetite and food intakeMixed
Very low evidence
Both-poles marker: glucagon's satiety effect is real but modest and the human evidence base is thin/dated (one small human test-meal study plus rodent mechanism); no...
SourceGeary N, Neurosci Biobehav Rev 1990;14(3):323-338Source
Full findingBoth-poles marker: glucagon's satiety effect is real but modest and the human evidence base is thin/dated (one small human test-meal study plus rodent mechanism); no modern human glucagon-infusion ad-libitum-intake study isolates a robust large anorectic effect, glucagon raises glucose (confounding the satiety read), and the dual-agonist contrast shows the GCGR arm does not carry oxyntomodulin's satiety. Competing pole: glucagon's headline therapeutic role is metabolic (glucose/EE), largely independent of its modest intake effect.
PopulationMulti-species synthesis
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsReused from corpus T9-GCGR-08. Explicit flag-both-poles record. Prevents the GCGR arm being written up as a confident appetite-suppressor.
LiraglutideMARKETED
Appetite and food intakeDecrease
Moderate evidence
Liraglutide (1.8 and 3.0 mg, 5 wk) reduced ad libitum energy intake at a test lunch by approximately 16% vs placebo in obese non-diabetic adults, increased...
Sourcevan Can J et al., Int J Obes (Lond) 2014;38(6):784-793Source
Full findingLiraglutide (1.8 and 3.0 mg, 5 wk) reduced ad libitum energy intake at a test lunch by approximately 16% vs placebo in obese non-diabetic adults, increased postprandial satiety/fullness and reduced hunger and prospective food consumption; authors concluded weight loss is appetite/intake-mediated, not expenditure-driven. 5-h gastric-emptying AUC was equivalent to placebo, but 1-h gastric emptying was 23% lower (3.0 mg, P=0.007) — an acute early-phase delay that does not persist.
Scope limitsSponsor-funded (Novo Nordisk); COI-flag. Reused from corpus T9-GLP1R-05.
Comparatorsplacebo
LiraglutideMARKETED
Appetite and food intakeDecrease
Low evidence
Liraglutide (escalated to 1.8 mg, 17 days) decreased activation of the parietal cortex (and, secondarily, insula and putamen reward regions) in response to highly...
SourceFarr OM et al., Diabetologia 2016;59(5):954-965Source
Full findingLiraglutide (escalated to 1.8 mg, 17 days) decreased activation of the parietal cortex (and, secondarily, insula and putamen reward regions) in response to highly desirable food images vs placebo in T2D, providing human fMRI evidence for a central/reward-system contribution to GLP-1R-mediated reduced food intake.
PopulationT2D, crossover RCT, n=18 analysed, 17 days
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitssmall sample (N~18)
Comparatorsplacebo
LiraglutideMARKETED
Appetite and food intakeDecrease
Low evidence
Liraglutide 1.8 mg reduced CNS (insula, putamen) responses to food pictures and enhanced the satiating effect of meals (putamen, amygdala) vs insulin glargine after 10...
SourceTen Kulve JS et al., Diabetes Care 2016;39(2):214-221Source
Full findingLiraglutide 1.8 mg reduced CNS (insula, putamen) responses to food pictures and enhanced the satiating effect of meals (putamen, amygdala) vs insulin glargine after 10 days, but these CNS differences were NO LONGER present after 12 weeks, suggesting the central food-cue/reward effect contributes to the induction of weight loss but not necessarily its maintenance.
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitssmall sample (N~20)
Comparatorsinsulin glargine
LiraglutideMARKETED
Appetite and food intakeDecrease
Very low evidence
The acute GLP-1R-mediated gastric-emptying delay is subject to tachyphylaxis under sustained exposure whereas the appetite/body-weight effect is not: in rats,...
SourceJelsing J et al., Diabetes Obes Metab 2012;14(6):531-538Source
Full findingThe acute GLP-1R-mediated gastric-emptying delay is subject to tachyphylaxis under sustained exposure whereas the appetite/body-weight effect is not: in rats, liraglutide's gastric-emptying inhibition was markedly diminished after 14 days while body-weight reduction persisted, indicating brain appetite signalling (not gastric emptying) is the main mechanism of liraglutide-induced weight loss.
PopulationRats (mechanistic)
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsReused from corpus T9-GLP1R-09. Mechanistic anchor reconciling why human steady-state studies find no GE delay yet large intake reduction.
In a phase 1a single/multiple-ascending-dose study in healthy participants, 4 weeks of orforglipron produced body-weight reductions up to 5.4 kg vs 2.4 kg placebo,...
SourcePratt E et al., Diabetes Obes Metab 2023;25(9):2634-2641Source
Full findingIn a phase 1a single/multiple-ascending-dose study in healthy participants, 4 weeks of orforglipron produced body-weight reductions up to 5.4 kg vs 2.4 kg placebo, decreased fasting glucose, and delayed gastric emptying on Day 28 — pharmacodynamics consistent with class GLP-1R appetite/satiety effects (intake not formally measured here).
PopulationHealthy adults, n=92 (32 SAD, 60 MAD), phase 1a
Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)
Intravenous oxyntomodulin reduced ad libitum energy intake at a buffet meal by ~19.3% and cumulative 12-h energy intake by ~11.3% in healthy normal-weight humans, with...
SourceCohen MA et al. (Bloom group), J Clin Endocrinol Metab 2003;88(10):4696-4701Source
Full findingIntravenous oxyntomodulin reduced ad libitum energy intake at a buffet meal by ~19.3% and cumulative 12-h energy intake by ~11.3% in healthy normal-weight humans, with reduced hunger, no nausea, no change in food palatability, and suppressed preprandial ghrelin. Combination (GLP-1R+GCGR) intake reduction; the glucagon-arm contribution cannot be isolated from this datum.
PopulationHealthy normal-weight humans
Fundingacademic - UK Medical Research Council and Wellcome Trust
Scope limitsReused from corpus T9-GCGR-05. Combination-only; per-receptor split not possible. Mechanistic contrast (Baggio 2004) indicates the satiety is GLP-1R-driven — not a positive GCGR satiety attribution.
Comparatorssaline
Oxyntomodulin (Gcgr-/- Vs Glp1r-/- Dissection)MARKETED
Appetite and food intakeNo change
Very low evidence
In mice, oxyntomodulin's acute food-intake suppression is mediated through the GLP-1 receptor, NOT the glucagon receptor: anorexia preserved in Gcgr-/- but abolished...
SourceBaggio LL, Huang Q, Brown TJ, Drucker DJ, Gastroenterology 2004;127(2):546-558Source
Full findingIn mice, oxyntomodulin's acute food-intake suppression is mediated through the GLP-1 receptor, NOT the glucagon receptor: anorexia preserved in Gcgr-/- but abolished in Glp1r-/-; only exendin-4 (not OXM) additionally reduced VO2/RQ, dissociating the intake effect (GLP-1R) from energy expenditure.
PopulationMice (receptor knockouts)
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsReused from corpus T9-GCGR-07. Negative/isolating-OUT for GCGR: GCGR arm does NOT carry the dual-agonist acute satiety. Mouse genetic KO; species caveat.
Comparatorsvehicle; exendin-4
RetatrutideINVESTIGATIONAL
Appetite and food intakeDecrease
Moderate evidence
In the retatrutide phase 2 T2D trial, pre-specified exploratory Appetite VAS showed retatrutide >=4 mg produced greater reductions in OVERALL appetite vs placebo...
SourceKanu C et al., Diabetes Obes Metab 2025;27(12):6988-6998Source
Full findingIn the retatrutide phase 2 T2D trial, pre-specified exploratory Appetite VAS showed retatrutide >=4 mg produced greater reductions in OVERALL appetite vs placebo (dose-dependent); the 0.5 mg group did not differ from placebo. First direct retatrutide appetite readout (in adults with T2D specifically).
PopulationAdults with T2D, n=275 efficacy set, phase 2
Fundingindustry-Eli Lilly
Scope limitsnot multiplicity-controlled; small sample (N~275); surrogate/exploratory endpoint
Comparatorsplacebo; dulaglutide 1.5 mg
RetatrutideINVESTIGATIONAL
Appetite and food intakeMixed
Moderate evidence
In the same retatrutide phase 2 T2D appetite analysis, individual VAS items moved heterogeneously: HUNGER fell vs placebo and PROSPECTIVE FOOD CONSUMPTION fell vs...
SourceKanu C et al., Diabetes Obes Metab 2025;27(12):6988-6998Source
Full findingIn the same retatrutide phase 2 T2D appetite analysis, individual VAS items moved heterogeneously: HUNGER fell vs placebo and PROSPECTIVE FOOD CONSUMPTION fell vs placebo, but SATIETY and FULLNESS showed NO significant retatrutide-vs-placebo difference at any timepoint over 36 weeks.
PopulationAdults with T2D, phase 2, over 36 weeks
Fundingindustry-Eli Lilly
Scope limitsnot multiplicity-controlled; small sample (N~275); surrogate/exploratory endpoint
Comparatorsplacebo; dulaglutide 1.5 mg
RetatrutideINVESTIGATIONAL
Appetite and food intakeDecrease
Moderate evidence
In the retatrutide phase 2 T2D Three-Factor Eating Inventory, higher doses reduced Perceived Hunger and Disinhibition and increased Dietary Restraint; retatrutide 12...
SourceKanu C et al., Diabetes Obes Metab 2025;27(12):6988-6998Source
Full findingIn the retatrutide phase 2 T2D Three-Factor Eating Inventory, higher doses reduced Perceived Hunger and Disinhibition and increased Dietary Restraint; retatrutide 12 mg also beat the dulaglutide arm on Perceived Hunger and Disinhibition at Week 36. No dietary calorie-intake records were collected, so no measured intake exists for retatrutide.
PopulationAdults with T2D, phase 2
Fundingindustry-Eli Lilly
Scope limitsnot multiplicity-controlled; small sample (N~275); surrogate/exploratory endpoint
Comparatorsplacebo; dulaglutide 1.5 mg
SemaglutideMARKETED
Appetite and food intakeDecrease
Moderate evidence
Once-weekly semaglutide 2.4 mg reduced ad libitum energy intake at an unrestricted lunch by 35% vs placebo at week 20; also reduced hunger and prospective food...
SourceFriedrichsen M et al., Diabetes Obes Metab 2021;23(3):754-762Source
Full findingOnce-weekly semaglutide 2.4 mg reduced ad libitum energy intake at an unrestricted lunch by 35% vs placebo at week 20; also reduced hunger and prospective food consumption, increased fullness/satiety, and improved Control of Eating with fewer/weaker cravings. The same study found NO delayed gastric emptying at week 20 (paracetamol AUC0-5h +8%, NS once body-weight corrected, P=0.12), attributing the intake drop to central appetite suppression rather than gastric slowing.
PopulationAdults with obesity; randomised placebo-controlled, week 20
Fundingindustry - Novo Nordisk (trial sponsor)
Scope limitsSponsor-authored (Novo Nordisk); COI-flag. Reused from corpus T9-GLP1R-01 (validated 2026-06-20). Central-vs-peripheral mechanism: intake reduction without persistent gastric-emptying delay.
Comparatorsplacebo
SemaglutideMARKETED
Appetite and food intakeDecrease
Moderate evidence
Once-weekly semaglutide (escalated to 1.0 mg, 12 wk) reduced total ad libitum energy intake across all meals by 24% vs placebo, with less hunger and fewer food...
SourceBlundell J et al., Diabetes Obes Metab 2017;19(9):1242-1251Source
Full findingOnce-weekly semaglutide (escalated to 1.0 mg, 12 wk) reduced total ad libitum energy intake across all meals by 24% vs placebo, with less hunger and fewer food cravings, better control of eating, and a lower preference for high-fat/energy-dense foods; resting metabolic rate adjusted for lean mass did not differ (i.e. weight loss is intake-driven, not expenditure-driven).
PopulationSubjects with obesity, n=30 crossover, 12 weeks
Fundingindustry - Novo Nordisk
Scope limitssmall sample (N~30)
Comparatorsplacebo
SemaglutideMARKETED
Appetite and food intakeDecrease
Moderate evidence
Oral semaglutide (escalated to 14 mg, 12 wk) reduced total daily ad libitum energy intake by 38.9% vs placebo in type 2 diabetes, with increased satiety/fullness after...
SourceGibbons C et al., Diabetes Obes Metab 2021;23(2):581-588Source
Full findingOral semaglutide (escalated to 14 mg, 12 wk) reduced total daily ad libitum energy intake by 38.9% vs placebo in type 2 diabetes, with increased satiety/fullness after a fat-rich breakfast, fewer cravings and better eating control.
PopulationSubjects with T2D, n=15 (13 evaluable), crossover, 12 weeks
Fundingindustry-Novo Nordisk
Scope limitssmall sample (N~15)
Comparatorsplacebo
SemaglutideMARKETED
Appetite and food intakeDecrease
Moderate evidence
Once-daily oral semaglutide 50 mg (20 wk) reduced ad libitum energy intake by 39.2 percentage points vs placebo in adults with obesity, with reduced hunger, increased...
SourceGabe MBN et al., Diabetes Obes Metab 2024;26(10):4480-4489Source
Full findingOnce-daily oral semaglutide 50 mg (20 wk) reduced ad libitum energy intake by 39.2 percentage points vs placebo in adults with obesity, with reduced hunger, increased fullness/satiety, fewer cravings and better control of eating, and no statistically significant difference in gastric emptying at week 20.
PopulationAdults with obesity, 20 weeks
Fundingindustry - Novo Nordisk (with Steno Diabetes Center Copenhagen)
Scope limitsSponsor-authored; COI-flag. Reused from corpus T9-GLP1R-04. Reinforces central (not gastric) mechanism at steady state.
Comparatorsplacebo
TirzepatideMARKETED
Appetite and food intakeDecrease
Low evidence
In a phase 1 mechanism-of-action trial in people with obesity (NCT04081337), tirzepatide reduced appetite and reduced calorie intake during an ad-libitum test meal vs...
SourceRavussin E, Sanchez-Delgado G, Martin CK, et al. Tirzepatide did not impact metabolic ada...Source
Full findingIn a phase 1 mechanism-of-action trial in people with obesity (NCT04081337), tirzepatide reduced appetite and reduced calorie intake during an ad-libitum test meal vs placebo, with increased fat oxidation and no impact on metabolic adaptation; energy expenditure was not increased. This is direct measured intake (unlike the retatrutide VAS-only data).
PopulationPeople with obesity, phase 1 MoA trial
Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)
Scope limitsanimal data; human relevance uncertain
Comparatorsplacebo
Tirzepatide|semaglutide (head-to-head)MARKETED
Appetite and food intakeNo change
Moderate evidence
Tirzepatide 15 mg gave greater fat-mass loss than semaglutide 1 mg in T2D, but the difference was NOT explained by ad libitum lunch energy intake, and 24-h intake /...
SourceHeise T et al., Diabetes Care 2023;46(5):998-1004Source
Full findingTirzepatide 15 mg gave greater fat-mass loss than semaglutide 1 mg in T2D, but the difference was NOT explained by ad libitum lunch energy intake, and 24-h intake / substrate utilisation / energy expenditure were not measured. No clean human tirzepatide-vs-semaglutide appetite/satiety differential isolating a GIP appetite contribution was located.
PopulationT2D, tirzepatide 15 mg vs semaglutide 1 mg
Fundingindustry - Eli Lilly and Company
Scope limitsReused from corpus T9-GIPR-06. Measured-null on the single acute intake readout; broader endpoints unmeasured. The within-molecule GIP appetite contribution in humans is proxy-only/unresolved.