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 PMID: 39495965, 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 imagingObesity
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 receptorWeeksNew 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
2016
Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO
Gaiser EC, Gallezot JD, Worhunsky PD, Jastreboff AM, Pittman B, Kantrovitz L, Angarita GA, Cosgrove KP, Potenza MN, Malison RT, Carson RE, Matuskey D. Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO. Neuropsychopharmacology 2016, 41: 3042-3050. PMID: 27374277, PMCID: PMC5101552, DOI: 10.1038/npp.2016.115.Peer-Reviewed Original ResearchConceptsBody mass indexVentral striatumObese individualsD2/3R availabilityOB individualsReward regionsSubstantia nigra/ventral tegmental areaDopamine D2/3 receptor availabilityNormal-weight individualsTreatment of obesityVentral tegmental areaNovel pharmacologic targetsD2/3 receptor availabilitySN/VTAAgonist tracersOverweight cohortMass indexWeight individualsTegmental areaBrain reward regionsAntagonist tracersPharmacologic targetReceptor availabilitySecondary analysisNW individuals