2025
Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial
Jastreboff A, Ryan D, Bays H, Ebeling P, Mackowski M, Philipose N, Ross L, Liu Y, Burns C, Abbasi S, Pannacciulli N. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial. New England Journal Of Medicine 2025, 393: 843-857. PMID: 40549887, DOI: 10.1056/nejmoa2504214.Peer-Reviewed Original ResearchBaseline to weekDose escalationTreatment of obesityTreatment policy estimandType 2 diabetesObese cohortBody weightDose-ranging trialPhase 2 trialGastrointestinal adverse eventsGlycated hemoglobin levelsPeptide-antibody conjugatesGlucagon-like peptide-1 receptor agonismIntention-to-treat approachOnce-monthlyDouble-blindPlacebo groupPlacebo-ControlledReceptor antagonismReceptor agonismHemoglobin levelsAdverse eventsPlaceboSafety signalsObesity83-OR: GLP-1RA Efficacy Doubled with Small Molecule Modulators of Pyruvate Kinase for Obesity Treatment
KIBBEY R, CARDONE R, RUZ-MALDONADO I, ZHAO X, BROWN S, FOSTER H, MERRINS M. 83-OR: GLP-1RA Efficacy Doubled with Small Molecule Modulators of Pyruvate Kinase for Obesity Treatment. Diabetes 2025, 74 DOI: 10.2337/db25-83-or.Peer-Reviewed Original ResearchGLP-1 RAsLean massCombo groupInsulin secretionOptimal treatment of obesityPreservation of lean massObesity treatmentTreatment groupsIslet healthCa2+ oscillationsCa2+ imagingFasting glucose levelsC57BL/6J male miceTreatment of obesityImproved insulin sensitivityGLP-1RAAUC glucoseOptimal treatmentDIO miceMale miceStudy endPlaceboGLP-1Body compositionInsulin sensitivityGDF8 and activin A blockade protects against GLP-1–induced muscle loss while enhancing fat loss in obese male mice and non-human primates
Mastaitis J, Gomez D, Raya J, Li D, Min S, Stec M, Kleiner S, McWilliams T, Altarejos J, Murphy A, Yancopoulos G, Sleeman M. GDF8 and activin A blockade protects against GLP-1–induced muscle loss while enhancing fat loss in obese male mice and non-human primates. Nature Communications 2025, 16: 4377. PMID: 40360507, PMCID: PMC12075787, DOI: 10.1038/s41467-025-59485-9.Peer-Reviewed Original ResearchConceptsGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsReceptor agonistsA blockadeGlucagon-like peptide-1 receptor agonist treatmentMuscle lossMuscle massFat lossObese male miceNon-human primatesType II activin receptorTreatment of obesityQuality of weight lossSignificant muscle lossIncrease muscle massEnhanced fat lossAgonist treatmentMale miceMuscle preservationAppetite suppressionActivin AActivin receptorsObese miceCaloric restrictionWeight loss
2024
Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE™‐1 and ‐2)
Wharton S, le Roux C, Kosiborod M, Platz E, Brueckmann M, Jastreboff A, Hussain S, Pedersen S, Borowska L, Unseld A, Kloer I, Kaplan L, committees and investigators T. Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE™‐1 and ‐2). Obesity 2024, 33: 67-77. PMID: 39495965, PMCID: PMC11664303, DOI: 10.1002/oby.24184.Peer-Reviewed Original ResearchTreatment of obesityBaseline BMIRandomized phase 3 clinical trialOnce-weekly subcutaneous injectionsPhase 3 clinical trialsBaseline to weekDouble-blind trialObesity-related complicationsBody weight reductionAbsence of T2DSystolic blood pressureLiver fat contentType 2 diabetesMagnetic resonance imagingMeasures of glycemiaSecondary endpointsDosing flexibilityProportion of participantsLifestyle modificationInvestigated glucagonSubcutaneous injectionBlood pressureBody compositionResonance imagingObesityBlack Tea Kombucha Consumption: Effect on Cardiometabolic Parameters and Diet Quality of Individuals with and without Obesity
Fraiz G, Costa M, Cardoso R, Hébert J, Zhao L, Corich V, Giacomini A, Milagro F, Barros F, Bressan J. Black Tea Kombucha Consumption: Effect on Cardiometabolic Parameters and Diet Quality of Individuals with and without Obesity. Fermentation 2024, 10: 384. DOI: 10.3390/fermentation10080384.Peer-Reviewed Original ResearchDiet qualityCardiometabolic parametersDiet quality of individualsDietary total antioxidant capacityWorsening diet qualityPre-post interventionHealthy eating patternsHealth of individualsTreatment of obesityIn vitro studiesPost-interventionHOMA-IREating patternsTotal cholesterolMetabolic healthObesityTotal antioxidant capacityDiet of individualsCompare differencesQuality of individualsAlkaline phosphataseIndividualsPositive impactDietHealth265-OR: Understanding Patterns of GLP-1/GLP-1 RA Use among Individuals with Type 1 Diabetes—A T1D Exchange (T1DX) Online Registry Analysis
MILLER K, NGUYEN H, SHERR J, KUDVA Y, CARLSON A, CHAYTOR N, DESALVO D, HILLIARD M, MARKS B, LITCHMAN M, BERGET C, WOLF W. 265-OR: Understanding Patterns of GLP-1/GLP-1 RA Use among Individuals with Type 1 Diabetes—A T1D Exchange (T1DX) Online Registry Analysis. Diabetes 2024, 73 DOI: 10.2337/db24-265-or.Peer-Reviewed Original ResearchAmerican Diabetes AssociationDiabetes AssociationPrevalence of obesityIncreasing prevalence of obesityCohort of adultsGLP-1National Institutes of HealthRegistry participantsInstitutes of HealthInternational Society for Pediatric and Adolescent DiabetesType 2 diabetesT1D ExchangeT1D adultsADA standardsOnline registryEducation specialistsMedian HbA1cGLP-1 therapyObesityCardiovascular diseaseIncreased prevalenceAdultsTreatment of obesityNational InstituteAdolescent Diabetes1886-LB: Safety, PK, and Preliminary Efficacy of the Liver-Targeted Mitochondrial Protonophore TLC-6740—A Phase 1 Study
GANE E, HUSS R, SUR J, MURAKAMI E, WENG S, KIRBY B, SHAH A, SHULMAN G, SUBRAMANIAN M, VIJAYAKUMAR A, MYERS R. 1886-LB: Safety, PK, and Preliminary Efficacy of the Liver-Targeted Mitochondrial Protonophore TLC-6740—A Phase 1 Study. Diabetes 2024, 73 DOI: 10.2337/db24-1886-lb.Peer-Reviewed Original ResearchTreatment of obesityAdverse eventsSteady-state half-lifeEvaluate food effectsPhase 1 studyDose-dependent improvementDose-dependent reductionProportion of subjectsUnrelated to treatmentDose-dependent mannerMAD cohortsLab abnormalitiesSerum totalLDL-CFood effectHealthy subjectsClinical useWeight lossImpact of foodBody weightPreliminary efficacyObesityHalf-lifeTreatmentMitochondrial uncoupling
2023
Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial
Garvey W, Frias J, Jastreboff A, le Roux C, Sattar N, Aizenberg D, Mao H, Zhang S, Ahmad N, Bunck M, Benabbad I, Zhang X, investigators S, Abalos F, Manghi F, Zaidman C, Vico M, Aizenberg D, Costanzo P, Serra L, MacKinnon I, Hissa M, Vidotti M, Saraiva J, Alves B, Franco D, Moratto O, Murthy S, Goyal G, Yamasaki Y, Sato N, Inoue S, Asakura T, Shestakova M, Khaykina E, Troshina E, Vorokhobina N, Ametov A, Tu S, Yang C, Lee I, Huang C, Ou H, Freeman G, Machineni S, Klein K, Sultan S, Parsa A, Otero-Martinez J, Gonzalez A, Bhargava A, Brian S, Ince C, Plantholt S, Cole J, Lacour A, Vega D, de Souza J, Rohlf J, St. John R, Horowitz B, Audish H, Galindo R, Umpiperrez G, Ard J, Curtis B, Garvey W, Fraser N, Mandry J, Mohseni R, Mayfield R, Powell T, Vance C, Ong S, Lewy-Alterbaum A, Murray A, Al-Karadsheh A, Yacoub T, Roberts K, Fried D, Rosenstock J, Pulla B, Bode B, Frias J, Klaff L, Brazg R, Van J, Tan A, Briskin T, Rhee M, Chaicha-Brom T, Hartley P, Nunez L, Cortes-Maisonet G, Soucie G, Hsia S, Jones T. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet 2023, 402: 613-626. PMID: 37385275, DOI: 10.1016/s0140-6736(23)01200-x.Peer-Reviewed Original ResearchConceptsType 2 diabetesBody mass indexTreatment discontinuationAdverse eventsBodyweight reductionWeight managementGlucagon-like peptide-1 receptor agonistsInteractive web response systemPeptide-1 receptor agonistsGlucose-dependent insulinotropic polypeptideComputer-generated random sequenceFrequent adverse eventsPlacebo-controlled trialSerious adverse eventsIncretin-based therapiesPhase 3 trialWeb response systemTreatment of obesityWeekly tirzepatideCoprimary endpointsRescue therapySafety endpointWeek 72Safety profileStudy treatmentTriple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial
Jastreboff A, Kaplan L, Frías J, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman M. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal Of Medicine 2023, 389: 514-526. PMID: 37366315, DOI: 10.1056/nejmoa2301972.Peer-Reviewed Original ResearchConceptsBody weightPercentage changePlacebo groupEnd pointGlucagon-like peptide-1Glucose-dependent insulinotropic polypeptideLower starting doseWeight-related conditionsCommon adverse eventsPlacebo-controlled trialPrimary end pointSecondary end pointsBody mass indexTreatment of obesityDose-dependent increaseDose-response relationshipWeight reductionStarting doseAdverse eventsInsulinotropic polypeptideHeart ratePeptide-1Side effectsGlucagon receptorWeeksRole of metformin in the management of type 2 diabetes: recent advances.
Gonzalez-Lopez C, Wojeck B. Role of metformin in the management of type 2 diabetes: recent advances. Polish Archives Of Internal Medicine 2023, 133 PMID: 37317976, DOI: 10.20452/pamw.16511.Peer-Reviewed Original ResearchConceptsType 2 diabetesAntidiabetic medicationsGlucagon-like peptide-1 receptor agonistsSodium-glucose cotransporter 2 inhibitorsPeptide-1 receptor agonistsCardio-renal protectionCotransporter 2 inhibitorsFirst-line agentsFirst-line therapyPolycystic ovary syndromeRole of metforminRisk of hypoglycemiaTreatment of obesityManagement of diabetesBlood glucose levelsMechanism of actionInitial therapyWay diabetesGestational diabetesOvary syndromeHeart failureRenal diseaseInsulin resistanceInsulin sensitivityReceptor agonistNew Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics
Jastreboff A, Kushner R. New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics. Annual Review Of Medicine 2023, 74: 125-139. PMID: 36706749, DOI: 10.1146/annurev-med-043021-014919.Peer-Reviewed Original ResearchConceptsGLP-1 RAsGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsAnti-obesity therapeuticsTreatment of obesityMechanism-based treatmentsNeurobiology of obesityObesity treatmentReceptor agonistGLP-1Obesity therapeuticsEffective treatmentObesityHalf of AmericansFirst agentTreatmentTherapeuticsAgonistsAgents
2022
Tirzepatide Once Weekly for the Treatment of Obesity
Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal Of Medicine 2022, 387: 205-216. PMID: 35658024, DOI: 10.1056/nejmoa2206038.Peer-Reviewed Original ResearchConceptsBody weightTreatment discontinuationAdverse eventsGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsGlucose-dependent insulinotropic polypeptidePercentage changeDose escalation periodWeight-related complicationsCommon adverse eventsCoprimary end pointsBody mass indexSubstantial global morbidityTreatment of obesityMean percentage changePercentage of participantsMean body weightWeight reductionCardiometabolic measuresTreat populationPlacebo groupWeek 72Mean BMIWeekly dosesDose escalation
2020
O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity
Yang Y, Fu M, Li MD, Zhang K, Zhang B, Wang S, Liu Y, Ni W, Ong Q, Mi J, Yang X. O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity. Nature Communications 2020, 11: 181. PMID: 31924761, PMCID: PMC6954210, DOI: 10.1038/s41467-019-13914-8.Peer-Reviewed Original ResearchMeSH KeywordsAcetylglucosamineAnimalsCell Line, TumorDietFastingGene DeletionHEK293 CellsHeLa CellsHomeostasisHumansIntra-Abdominal FatLipolysisMaleMiceMice, Inbred C3HMice, Inbred C57BLMice, KnockoutN-AcetylglucosaminyltransferasesObesityPerilipin-1PhosphorylationProtein Processing, Post-TranslationalSignal TransductionConceptsDiet-induced obesityVisceral fatExcessive visceral fat accumulationPerilipin 1Visceral fat accumulationVisceral fat lossTreatment of obesityPrimary risk factorAdipose tissue homeostasisUnhealthy obesityRisk factorsEnhanced lipolysisInhibits lipolysisFat accumulationO-GlcNAcylationFat lossObesityFat lipolysisRelated diseasesLipolysisInducible deletionLipid dropletsHexosamine biosynthetic pathwayFatTissue homeostasis
2019
Cardiac Risk Factor Improvement Following Bariatric Surgery
Kitamura R, Morton J, Eisenberg D. Cardiac Risk Factor Improvement Following Bariatric Surgery. 2019, 519-526. DOI: 10.1007/978-3-030-27021-6_46.Peer-Reviewed Original ResearchCoronary artery diseaseCardiovascular diseaseBariatric surgeryObese populationWeight lossCholesterol-lowering medicationsIntentional weight lossWeight loss surgeryRisk factor improvementsTreatment of obesityCause of deathSignificant weight lossMarkers of diseaseArtery diseaseBlood pressureCAD riskAsymptomatic populationCessation effortsHeart diseaseRisk factorsPredictive valueAdult menStrong dataDiseaseSurgery
2018
Comorbidity Remission Following Intragastric Dual Balloon Placement
Garcia L, Vajanaphanich S, Morton JM. Comorbidity Remission Following Intragastric Dual Balloon Placement. Obesity Surgery 2018, 29: 353-355. PMID: 30382461, DOI: 10.1007/s11695-018-3564-6.Peer-Reviewed Original ResearchConceptsComorbidity remissionBalloon placementDual balloonWeight lossWeight loss 6Treatment of obesityEarly-stage obesityBalloon insertionBiochemical improvementBlood pressureSingle institutionLipid profileEfficacious interventionsDemographic dataPatientsRemissionObesityMonthsSignificant improvementBalloonBiochemical dataPlacementAcute physical exercise increases leptin‐induced hypothalamic extracellular signal‐regulated kinase1/2 phosphorylation and thermogenesis of obese mice
Gaspar R, Muñoz V, Kuga G, Nakandakari S, Minuzzi L, Botezelli J, da Silva A, Cintra D, de Moura L, Ropelle E, Pauli J. Acute physical exercise increases leptin‐induced hypothalamic extracellular signal‐regulated kinase1/2 phosphorylation and thermogenesis of obese mice. Journal Of Cellular Biochemistry 2018, 120: 697-704. PMID: 30206970, DOI: 10.1002/jcb.27426.Peer-Reviewed Original ResearchConceptsAcute physical exerciseBrown adipose tissueObese micePhysical exerciseEnergy expenditureERK1/2 phosphorylationTreatment of obesityExtracellular signal-regulated kinase1/2 (ERK1/2) phosphorylationProtein 1 (UCP1) contentExtracellular signal-regulated kinase 1/2Signal-regulated kinase 1/2Sympathetic signalsSpontaneous activityAdipose tissueP-ERK1/2Main interventionThermoregulatory effectsMiceKey mediatorThermogenesisOxygen uptakeMolecular changesKinase 1/2ObeseObesityBariatric Surgery: Current State of Affairs
Blevins K, Azagury D, Morton J. Bariatric Surgery: Current State of Affairs. 2018, 17-20. DOI: 10.1007/978-3-319-93545-4_2.Peer-Reviewed Original ResearchWhy Weight? An Analytic Review of Obesity Management, Diabetes Prevention, and Cardiovascular Risk Reduction
Igel L, Saunders K, Fins J. Why Weight? An Analytic Review of Obesity Management, Diabetes Prevention, and Cardiovascular Risk Reduction. Current Atherosclerosis Reports 2018, 20: 39. PMID: 29785665, DOI: 10.1007/s11883-018-0740-z.Peer-Reviewed Original ResearchConceptsInsurance coveragePrevent Type 2 DiabetesExpanded insurance coverageEndoscopic bariatric therapiesAnti-obesity pharmacotherapyCardiovascular risk reductionEnd-stage sequelaeAnti-diabetic medicationsDiabetes preventionLifestyle interventionCare-thatComplications of T2DMWeight-loss devicesWeight managementTreatment of obesityObesity managementType 2 diabetesRisk reduction purposesDisease preventionT2DM managementBariatric therapiesDisease managementBariatric surgeryMortality benefitObesityFood Cues and Obesity: Overpowering Hormones and Energy Balance Regulation
Belfort-DeAguiar R, Seo D. Food Cues and Obesity: Overpowering Hormones and Energy Balance Regulation. Current Obesity Reports 2018, 7: 122-129. PMID: 29619632, PMCID: PMC5959777, DOI: 10.1007/s13679-018-0303-1.BooksConceptsEnergy balance regulationFood cuesObesity epidemicBalance regulationTreatment of obesityDevelopment of obesityPoor treatment outcomesFood cue exposureFood cue reactivityPurpose of ReviewInModern obesogenic environmentFood cue responsesObese individualsWeight managementTreatment outcomesFood intakeCue-elicited responsesPsychosocial interventionsObesityConventional treatmentObesogenic environmentCue exposurePhysiology of feedingCue reactivityHormone
2017
Inactivation of SPAK kinase reduces body weight gain in mice fed a high-fat diet by improving energy expenditure and insulin sensitivity
Torre-Villalvazo I, Cervantes-Pérez L, Noriega L, Jiménez J, Uribe N, Chávez-Canales M, Tovar-Palacio C, Marfil-Garza B, Torres N, Bobadilla N, Tovar A, Gamba G. Inactivation of SPAK kinase reduces body weight gain in mice fed a high-fat diet by improving energy expenditure and insulin sensitivity. AJP Endocrinology And Metabolism 2017, 314: e53-e65. PMID: 29066461, DOI: 10.1152/ajpendo.00108.2017.Peer-Reviewed Original ResearchConceptsSTE20/SPS1-related proline-alanine-rich protein kinaseInsulin sensitivityHigh-fat dietGlucose toleranceElectroneutral cation-chloride cotransportersEnergy expenditureResistant to HFD-induced obesityAssociated with decreased blood pressureTransepithelial salt transportRegulation of energy balanceCation-chloride cotransportersTreatment of obesityAdipose tissue hypertrophyReduced body weight gainWhole-body insulin sensitivityObesity susceptibility genesWhite adipose tissue hypertrophyWeight gainHFD-induced obesitySLC12 familySPAK kinaseMetabolic syndromeTissue hypertrophyEvaluate weight gainBlood pressure
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