Explore studies of glp 1.
Gastric pacing in morbidly obese patients altered circulating CCK, somatostatin, and leptin levels, providing a neuroendocrine mechanism for the satiety and weight loss effects of this device.
Cigaina, Valerio; Hirschberg, Angelica L · Clinical Trial
Satiety is controlled by a two-tier peripheral signaling system: short-term gut peptides (CCK, GLP-1, PYY, ghrelin, oxyntomodulin) for meal control and long-term adiposity signals (leptin, insulin) for body weight regulation, integrated by brainstem and hypothalamic circuits.
Drazen, Deborah L; Woods, Stephen C · Review
CCK and GLP-1 are the most validated satiety biomarkers correlating with both subjective appetite ratings and actual food intake, with PYY, ghrelin, insulin, and glucose providing complementary information in multi-marker panels.
de Graaf, Cees; Blom, Wendy A M; Smeets, Paul A M; Stafleu, Annette; Hendriks, Henk F J · Review
At least 8 gut/pancreatic hormones regulate satiety, with GLP-1, PYY, and amylin identified as the most promising therapeutic targets for obesity — with combination therapy suggested for superior outcomes.
Druce, Maralyn R; Small, Caroline J; Bloom, Stephen R · Review
Human appetite is regulated by a multi-level system including adiposity signals (leptin, insulin), gut peptides (GLP-1, PYY, CCK, ghrelin), and hypothalamic neuropeptides (NPY, AgRP, POMC), with GLP-1 and PYY identified as the most druggable targets.
Halford, Jason C G; Cooper, Gillian D; Dovey, Terence M · Review
Normal, obese, and binge-eating individuals show distinct patterns of appetite signal dysfunction across peripheral (gut peptides, adipokines) and central (hypothalamic neuropeptide) systems — disorder-specific signaling profiles enabling targeted treatment.
Hellström, Per M; Geliebter, Allan; Näslund, Erik; Schmidt, Peter T; Yahav, Eric K; Hashim, Sami A; Yeomans, Martin R · Review
Food intake control operates through an integrated brain-gut axis where peripheral peptides (GLP-1, PYY, CCK, ghrelin, amylin) signal via vagal and hormonal routes to central circuits (NPY/AgRP, POMC/CART, CRF) for coordinated appetite regulation.
Konturek, S J; Konturek, J W; Pawlik, T; Brzozowski, T · Review
Gut peptide-based obesity drugs including GLP-1 agonists, PYY analogs, oxyntomodulin, and ghrelin antagonists represent the most promising peripheral anti-obesity targets, with GLP-1 showing the most advanced clinical development.
Scharf, Matthew T; Ahima, Rexford S · Review
Eating behavior in obesity reflects disrupted multi-level peptide signaling: blunted gut satiety peptides (GLP-1, PYY, CCK), altered opioid reward processing, ghrelin dysregulation, and impaired central neuropeptide circuits — biology driving behavioral excess.
Schwartz, Gary J · Review
Peripheral gut hormone-based obesity drug development focuses on GLP-1 agonists (most advanced), PYY analogs, oxyntomodulin, amylin analogs, and PP as practical anti-obesity drug targets with established physiological rationale and clinical precedent.
Small, Caroline J; Bloom, Stephen R · Review
Gut hormones (GLP-1, PYY, ghrelin, CCK, oxyntomodulin) regulate body weight through coordinated appetite and energy expenditure signaling, with GLP-1 receptor agonists showing the most advanced clinical development for obesity treatment.
Wynne, Katie; Stanley, Sarah; Bloom, Steve · Review
Post-prandial gut hormones (GLP-1, PYY, CCK, oxyntomodulin) signal satiety through vagal and bloodstream pathways to brainstem/hypothalamic circuits, with combination peptide mimicry showing greater satiety than single agents — the future of appetite pharmacology.
Bloom, Steve; Wynne, Katie; Chaudhri, Owais · Review
Combined CCK and GLP-1 infusion produced additive effects on appetite suppression and antropyloroduodenal motility in healthy humans — supporting combination gut peptide therapy for superior satiety and weight management.
Brennan, Ixchel M; Feltrin, Kate L; Horowitz, Michael; Smout, Andre J P M; Meyer, James H; Wishart, Judith; Feinle-Bisset, Christine · RCT
Palatable food disrupts appetite regulation through opioid reward pathway overactivation (hedonic eating), blunted satiety peptide responses (GLP-1, PYY, CCK), and altered ghrelin dynamics — creating a multi-level biological mechanism for food addiction and overconsumption.
Erlanson-Albertsson, Charlotte · Review
Lactitol colonic fermentation increased circulating PYY and GLP-1 in rats and humans, establishing that short-chain fatty acid production from dietary fiber fermentation stimulates L-cell satiety peptide secretion — a prebiotic mechanism for appetite regulation.
Gee, Jennifer M; Johnson, Ian T · Clinical Trial
Ghrelin-leptin cross-talk through the brain-gut axis constitutes the core energy balance system, integrating with GLP-1, PYY, NPY, and melanocortin circuits — obesity results from disruption of this integrated network.
Popovic, Vera; Duntas, Leonidas H · Review
Children with anorexia nervosa demonstrated disrupted entero-insular axis responses: abnormal GLP-1, insulin, glucose, and gut peptide dynamics after meals compared to healthy controls — gut hormone dysfunction may perpetuate the disease beyond psychological factors.
Tomasik, Przemyslaw J; Sztefko, Krystyna; Starzyk, Jerzy; Rogatko, Iwona; Szafran, Zdzisław · Clinical Trial
PYY3-36 and GLP-1-mediated appetite suppression required proper mouse acclimatization and habituation to experimental conditions; non-acclimatized mice showed variable, unreliable anorectic responses — explaining conflicting literature results.
Abbott, C R; Small, C J; Sajedi, A; Smith, K L; Parkinson, J R C; Broadhead, L L; Ghatei, M A; Bloom, S R · Animal Study
GLP-1 and PYY3-36 progressively increased over months post-RYGB, with the rise correlating with reduced appetite and sustained weight loss — gut hormonal adaptation (not just restriction) explains bariatric surgery's long-term success.
Borg, C M; le Roux, C W; Ghatei, M A; Bloom, S R; Patel, A G; Aylwin, S J B · Cohort
Comprehensive mapping of GI appetite hormones: ghrelin as the sole orexigenic signal; GLP-1, PYY3-36, oxyntomodulin, CCK, amylin, PP, and bombesin/GRP as anorexigenic signals — each acting through distinct receptors and pathways for integrated satiety control.
Chaudhri, Owais; Small, Caroline; Bloom, Steve · Review
Peripheral gut peptides (GLP-1, PYY, CCK, ghrelin) converge on the hypothalamic melanocortin system (POMC/AgRP neurons) as the central integration point, with melanocortin neurons serving as the final common pathway translating gut signals into eating behavior.
Ellacott, Kate L J; Halatchev, Ilia G; Cone, Roger D · Review
The gut-brain glucose regulatory axis operates through incretin peptides (GLP-1, GIP), neural signals, and other gut hormones to control glucose metabolism — pharmacological exploitation has produced GLP-1 agonists and DPP-4 inhibitors as major diabetes drug classes.
Heijboer, A C; Pijl, H; Van den Hoek, A M; Havekes, L M; Romijn, J A; Corssmit, E P M · Review
RYGB produced significantly greater postprandial GLP-1 and PYY3-36 increases and greater ghrelin suppression than gastric banding, with hormonal changes correlating with superior weight loss — gut hormone modification, not restriction alone, explains bypass superiority.
Korner, Judith; Inabnet, William; Conwell, Irene M; Taveras, Carmen; Daud, Amna; Olivero-Rivera, Lorraine; Restuccia, Nancy L; Bessler, Marc · Cross Sectional
Bariatric surgery produced comprehensive gut hormone profile transformation: elevated GLP-1, PYY3-36, and oxyntomodulin with suppressed ghrelin, creating an anorectic hormonal milieu that facilitates weight loss and improves glucose metabolism beyond mechanical restriction.
le Roux, Carel W; Aylwin, Simon J B; Batterham, Rachel L; Borg, Cynthia M; Coyle, Frances; Prasad, Vyas; Shurey, Sandra; Ghatei, Mohammad A; Patel, Ameet G; Bloom, Stephen R · Clinical Trial
Complete 2006 mapping of gut peptide appetite regulation: GLP-1 and PYY3-36 as top obesity targets, with CCK, oxyntomodulin, amylin, and PP providing complementary satiety signals — ghrelin as the sole orexigenic gut peptide.
Murphy, Kevin G; Dhillo, Waljit S; Bloom, Stephen R · Review
PI3K-gamma was identified as an essential mediator of GLP-2's intestinal mucosal growth effects, with PI3K-gamma knockout mice showing impaired GLP-2-stimulated mucosal proliferation — mapping the signal transduction for gut peptide-driven intestinal repair.
Anini, Younes; Izzo, Angelo; Oudit, Gavin Y; Backx, Peter H; Brubaker, Patricia L · Animal Study
GLP-1 and GIP are both released within minutes of eating and help the body process nutrients by stimulating insulin release from pancreatic beta cells. Both peptides promote beta-cell growth and protect these cells from dying. However, the two peptides differ in important ways. GIP promotes fat storage and strengthens bones by stimulating bone-building cells. GLP-1, on the other hand, slows stomach emptying, suppresses glucagon (a sugar-raising hormone), promotes feelings of fullness, and is associated with weight loss. Both peptides are rapidly broken down by the enzyme DPP-4, which led to two classes of diabetes drugs: degradation-resistant GLP-1 receptor agonists and DPP-4 inhibitors. These therapies lower HbA1c without causing weight gain in people with type 2 diabetes.
Baggio, Laurie L; Drucker, Daniel J · Review
GLP-1 receptor agonists and DPP-4 inhibitors exploit the incretin system for diabetes treatment, providing glucose-dependent insulin stimulation, weight loss (GLP-1 agonists), and low hypoglycemia risk — the most significant new diabetes drug class.
Green, Dina E · Review
Carbohydrate restriction in metabolic syndrome patients modified gut peptide profiles (reduced ghrelin, altered PYY) and adipokine levels (decreased leptin, increased adiponectin), with hormonal changes correlating with weight loss and improved metabolic markers.
Hayes, Matthew R; Miller, Carla K; Ulbrecht, Jan S; Mauger, Joanna L; Parker-Klees, Lynn; Gutschall, Melissa Davis; Mitchell, Diane C; Smiciklas-Wright, Helen; Covasa, Mihai · Clinical Trial
Enhanced GLP-1 and PYY responses with suppressed ghrelin after RYGB mediated sustained appetite reduction and weight loss, with gut hormone changes persisting years post-surgery — establishing hormonal modification (not just restriction) as the primary mechanism of bariatric success.
le Roux, Carel W; Welbourn, Richard; Werling, Malin; Osborne, Alan; Kokkinos, Alexander; Laurenius, Anna; Lönroth, Hans; Fändriks, Lars; Ghatei, Mohammad A; Bloom, Stephen R; Olbers, Torsten · Clinical Trial
GI neuroendocrine satiety regulation integrates gut peptide signals (GLP-1, PYY, CCK, oxyntomodulin, ghrelin), enteric neural pathways, and central melanocortin/NPY circuits for comprehensive food intake control — gut peptide drugs leading the obesity treatment pipeline.
Maljaars, J; Peters, H P F; Masclee, A M · Review
The appetite signaling chain: food → gut peptide release (GLP-1, PYY, CCK, ghrelin) → enteric nerve detection → vagal afferent transmission → brainstem integration (NTS) → hypothalamic processing (arcuate) → behavioral output — the complete food-to-decision neural-humoral pathway.
Näslund, Erik; Hellström, Per M · Review
Post-meal fullness involves two phases: satiation (meal termination via vagal mechanoreception + CCK) and sustained satisfaction (inter-meal fullness via GLP-1, PYY, insulin, leptin) — distinguishing the immediate fullness signal from prolonged appetite suppression for targeted drug development.
Berthoud, H-R · Review
Orlistat inhibition of intestinal lipase acutely increased appetite and attenuated GLP-1/PYY satiety responses, proving that fat absorption (not just fat presence) is required for satiety hormone release — the gut must PROCESS fat to signal fullness.
Ellrichmann, Mark; Kapelle, Mario; Ritter, Peter R; Holst, Jens J; Herzig, Karl-Heinz; Schmidt, Wolfgang E; Schmitz, Frank; Meier, Juris J · RCT
Obese women with BED showed distinct postprandial gut peptide profiles (altered ghrelin, PYY3-36, GLP-1) compared to non-binge obese controls, identifying BED-specific gut hormone dysfunction beyond general obesity-related appetite changes.
Geliebter, Allan; Hashim, Sami A; Gluck, Marci E · Clinical Trial
Postprandial GLP-1, PYY3-36, and other gut regulatory peptides dramatically increased following gastric bypass, with enhanced hormonal satiety signaling correlating with reduced appetite and caloric intake — hormonal reprogramming, not restriction, as the primary surgical mechanism.
Holdstock, C; Zethelius, B; Sundbom, M; Karlsson, F A; Edén Engström, B · Clinical Trial
Different macronutrients trigger distinct gut peptide profiles: protein produces the strongest and most diverse satiety peptide response (GLP-1, PYY, CCK); fat strongly triggers CCK/GLP-1; carbohydrate mainly GIP/insulin; fiber enhances GLP-1/PYY through fermentation — macronutrient-specific appetite pharmacology.
Karhunen, L J; Juvonen, K R; Huotari, A; Purhonen, A K; Herzig, K H · Review
Hormone-based fuel metabolism drugs span GLP-1 agonists (semaglutide class), amylin analogs (pramlintide), PYY analogs, and ghrelin modulators for integrated obesity/diabetes treatment — exploiting endogenous regulatory peptide systems for superior metabolic control.
Kesty, Nicole C; Roth, Jonathan D; Maggs, David · Review
New diabetes drugs include GLP-1 agonists (exenatide, liraglutide: injectable, weight loss, low hypo risk), DPP-4 inhibitors (sitagliptin, vildagliptin: oral, weight neutral), and amylin analog (pramlintide) — peptide-based drugs transforming type 2 diabetes treatment.
Krentz, Andrew J; Patel, Mayank B; Bailey, Clifford J · Review
GLP-1 agonists and DPP-4 inhibitors combine synergistically with metformin (first-line), sulfonylureas, thiazolidinediones, and insulin for T2DM, with combination selection guided by patient weight, hypo risk, and HbA1c target — practical combination pharmacotherapy guidance.
Over, Rebecca K; Ratner, Robert E · Review
Managed care analysis of exenatide (GLP-1 agonist: weight loss, injectable), sitagliptin (DPP-4 inhibitor: oral, weight neutral), and pramlintide (amylin analog: injectable, weight loss) for T2DM positioning — incretin drugs transforming diabetes pharmacotherapy economics.
VanDeKoppel, Shawna; Choe, Hae Mi; Sweet, Burgunda V · Review
Both GLP-1 drugs tested — exenatide (a GLP-1 receptor agonist) and sitagliptin (a DPP-4 inhibitor) — caused significant pancreatic injury in mice compared to controls. The damage included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. Importantly, a high-fat diet made everything worse. Mice fed a high-fat diet already showed increased pancreatic changes compared to standard-diet mice, and when GLP-1 drugs were added on top of a high-fat diet, the pancreatic injury was exacerbated. Pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly elevated in high-fat diet mice regardless of drug treatment.
Rouse, Rodney; Xu, Lin; Stewart, Sharron; Zhang, Jun · Animal Study
In the landmark SUSTAIN-6 trial, weekly semaglutide reduced the rate of major cardiovascular events (cardiovascular death, nonfatal heart attack, or nonfatal stroke) by 26% compared to placebo in patients with type 2 diabetes at high cardiovascular risk (hazard ratio 0.74; 95% CI 0.58–0.95; P<0.001 for noninferiority). The composite primary endpoint occurred in 6.6% of semaglutide patients versus 8.9% of placebo patients over 104 weeks. Nonfatal stroke was reduced by 39% (HR 0.61; P=0.04) and nonfatal heart attack by 26% (HR 0.74; P=0.12, not statistically significant). Rates of new or worsening kidney disease were also lower with semaglutide. However, the trial flagged an unexpected safety signal: retinopathy complications were significantly higher with semaglutide (HR 1.76; P=0.02), a finding that required further investigation.
Marso, Steven P; Bain, Stephen C; Consoli, Agostino; Eliaschewitz, Freddy G; Jódar, Esteban; Leiter, Lawrence A; Lingvay, Ildiko; Rosenstock, Julio; Seufert, Jochen; Warren, Mark L; Woo, Vincent; Hansen, Oluf; Holst, Anders G; Pettersson, Jonas; Vilsbøll, Tina · Rct
This review maps out the landscape of peptide receptors on pancreatic beta cells that can be targeted for diabetes treatment. Beyond the well-known GLP-1 receptor, it covers GIP, glucagon, somatostatin, pancreatic polypeptide, CCK, PYY, oxyntomodulin, and ghrelin receptors — all G-protein coupled receptors (GPCRs) that regulate insulin secretion and metabolism. Critically, the review highlights the emerging strategy of dual and triple agonist peptides that activate two or more of these receptors simultaneously. It also covers fatty acid GPCRs (GPR40, GPR41, GPR43, GPR84, GPR119, GPR120) that regulate peptide hormone secretion and represent additional drug targets.
Moran, Brian M; McKillop, Aine M; O'Harte, Finbarr Pm · Review
Replacing sucrose with the low-calorie bulk sweetener erythritol in test meals did not change post-meal GLP-1 or PYY gut hormone levels, and did not affect how much food people ate afterward or their preference for sweet foods. Both lean and obese participants showed similar gut hormone responses regardless of whether the meal contained sucrose or erythritol. The one notable difference: when lean participants ate a larger-volume isocaloric erythritol meal, they reported less hunger than after the sucrose control meal (p=0.003) — likely a volume effect rather than a sweetener effect. This volume-related hunger reduction was not seen in obese participants.
Overduin, Joost; Collet, Tinh-Hai; Medic, Nenad; Henning, Elana; Keogh, Julia M; Forsyth, Faye; Stephenson, Cheryl; Kanning, Marja W; Ruijschop, Rianne M A J; Farooqi, I Sadaf; van der Klaauw, Agatha A · Rct
Using a sustained-release oxyntomodulin analogue (OX-SR) in rats, researchers definitively showed that the energy expenditure (calorie-burning) effect of oxyntomodulin occurs through the glucagon receptor, not the GLP-1 receptor. When the GLP-1 receptor was blocked with Exendin 9-39, OX-SR still increased oxygen consumption (energy burning). But when glucagon receptor activity was eliminated, the energy expenditure boost completely disappeared. This resolves a key controversy about how oxyntomodulin works: its appetite-suppressing effects come mainly through GLP-1 receptor activation, while its calorie-burning effects require glucagon receptor activation. Both receptor activities are needed for optimal weight loss.
Scott, R; Minnion, J; Tan, T; Bloom, S R · Animal
An independent expert panel reviewed all suspected pancreatitis cases across the entire HARMONY Phase III clinical program for albiglutide (a GLP-1 receptor agonist). Of 4,895 patients studied, 43 had potential pancreatitis cases, of which 11 were adjudicated as definite or probable acute pancreatitis (8 on albiglutide, 3 on active comparators). The pancreatitis rate with albiglutide was 0.3% (6/2,365) compared to 0% with placebo (0/486) and 0.08% with non-GLP-1RA active comparators (2/2,062 — but both confirmed cases in the comparator group were actually in patients receiving a different GLP-1RA). While pancreatitis was uncommon overall, the rate was numerically higher with albiglutide than placebo, and the independent committee judged most cases as at least possibly related to the drug.
Al-Kawas, Firas; Anderson, Michelle Ann; Enns, Robert; Wilson, Timothy H; Johnson, Susan; Mallory, Jason M · Post Hoc Analysis
GLP-1 receptor agonist drugs reduce body weight by activating the same brain circuits that are naturally engaged by gut-derived GLP-1 after eating and by bariatric surgery.
Grill, Harvey J · Review
Exenatide significantly attenuated resting forearm blood flow (FBF) at 3 hours after the meal (P = 0.003) and showed a trend at 6 hours (P = 0.056) compared to placebo. This means exenatide blunted the vasodilation (blood vessel widening) that normally happens after eating. Exenatide also had beneficial metabolic effects: it prevented the post-meal glucose spike (glucose actually decreased at 2 hours while it rose with placebo and saxagliptin) and abated the transient triglyceride increase. Only the exenatide group did not show a significant insulin surge. No differences were found in peak forearm blood flow, plasma nitrotyrosine (an oxidative stress marker), or plasma 8-iso-prostaglandin F2alpha between groups. Free fatty acids declined in all groups but less markedly with exenatide. The researchers concluded the vascular effects were primarily endothelium-independent, meaning exenatide altered blood flow through mechanisms other than the vessel lining's nitric oxide system.
Hamidi, Vala; Riggs, Kayla; Zhu, Liang; Bermudez Saint Andre, Karla; Westby, Christian; Coverdale, Sara; Dursteler, Amy; Wang, Hongyu; Miller Iii, Charles; Taegtmeyer, Heinrich; Gutierrez, Absalon D · Randomized Controlled Crossover Trial
The cost-of-control analysis compared oral semaglutide 14 mg against six injectable GLP-1 receptor agonists for type 2 diabetes. The calculation divides annual drug cost by the proportion of patients reaching HbA1c targets. For the HbA1c ≤6.5% target, costs per patient achieving control: injectable semaglutide 1 mg was cheapest at $15,430, followed by oral semaglutide 14 mg at $17,383. All others (dulaglutide, exenatide once-weekly and twice-daily, liraglutide, lixisenatide) cost more per controlled patient. For HbA1c <7.0%: injectable semaglutide 1 mg led at $12,627, followed by oral semaglutide at $13,493. The pattern was consistent. Oral semaglutide was likely cost-effective versus all comparators except injectable semaglutide. This matters because some patients strongly prefer pills over injections.
Hansen, B B; Nuhoho, S; Ali, S N; Dang-Tan, T; Valentine, W J; Malkin, S J P; Hunt, B · Cost Effectiveness Analysis