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RESEARCH PRODUCT

Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial

Hw RodbardJ RosenstockLh CananiC DeerochanawongJ5 GumprechtSø LindbergI LingvayAl SøndergaardMb TreppendahlE MontanyaP CruzL LoredoC LuquezM MoiselloGa AugustoM CastroL CananiBranko AkrapTomislav BulumDario RahelićIvana ŠUnić-grčićSrećko TušekI AvramidisM BenroubiT DidangelosG KarousosE PagkalosC SampanisM SomaliZ DomboróczkiP FaludiZ GaálP Kis- GombosG KocsisZ MartonZ SudárS BuscemiA Di CarloF DottaA GambineriD LauroM MaranghiM ArciszewskaJ GumprechtK MatuszewskaE SkokowskaT StasinskaS FeofanovaE FilippovaG GalstyanL GaysinaM KunitsynaL SuplotovaS AnticA DjukicM MitrovicM PesicE StokicE JodarE MartínezPm RayaE MontanyaCm PortilloMp VeraMr FernándezP San JoseMt RieraA BoonyavarakulC DeerochanawongA SriwijitkamolD AjaniE ArmasK Barbel- JohnsonD BartilucciG BonabiR BuschD ButukK CannonC ChaseL ChaykinV CheekatiT DavisB DelgadoN FarrisM GravesC HaL HarperS HerringM HewittD HsiaR JacksonM JardulaM JoyceM JuarezA KapoorD KarounosD KayneA LacourG LedesmaI LingvayR LipetzJ LomboyS LyndE MorawskiR MorinR MurphyJs OvercashJ PullmanHw RodbardJ RosenstockG RuoffD SteenkampH ToroD TrachtenbargB TullochA WeisbrotA. Wright

subject

MaleSettore MED/09 - Medicina InternaEndocrinology Diabetes and MetabolismGlucagon-Like PeptidesAdministration OralType 2 diabeteslaw.inventionSettore MED/13 - Endocrinologia0302 clinical medicineGlucosidesRandomized controlled triallaw030212 general & internal medicineSettore MED/49 - Scienze Tecniche Dietetiche ApplicateBenzhydryl CompoundMiddle AgedMetforminMetforminTreatment Outcomediabetes mellitusDrug Therapy CombinationFemalemedicine.drugHumanAdultmedicine.medical_specialtyGlucagon-Like PeptideGlucosideUrology030209 endocrinology & metabolism03 medical and health sciencesPharmacotherapyDouble-Blind MethodWeight Loss.Diabetes mellitusWeight LossInternal MedicinemedicineEmpagliflozinHumansHypoglycemic AgentsBenzhydryl CompoundsGlycated HemoglobinAdvanced and Specialized NursingHypoglycemic Agentbusiness.industrySemaglutidemedicine.diseaseDiscontinuationDiabetes Mellitus Type 2business

description

OBJECTIVE Efficacy and safety of the glucagon-like peptide 1 (GLP-1) analog oral semaglutide and the sodium–glucose cotransporter 2 inhibitor empagliflozin were compared in patients with type 2 diabetes uncontrolled on metformin. RESEARCH DESIGN AND METHODS Patients were randomized to once-daily open-label treatment with oral semaglutide 14 mg (n = 412) or empagliflozin 25 mg (n = 410) in a 52-week trial. Key end points were change from baseline to week 26 in HbA1c (primary) and body weight (confirmatory secondary). Two estimands addressed efficacy-related questions: treatment policy (regardless of trial product discontinuation or rescue medication) and trial product (on trial product without rescue medication) in all randomized patients. RESULTS Four hundred (97.1%) patients in the oral semaglutide group and 387 (94.4%) in the empagliflozin group completed the trial. Oral semaglutide provided superior reductions in HbA1c versus empagliflozin at week 26 (treatment policy –1.3% vs. –0.9% [–14 vs. –9 mmol/mol], estimated treatment difference [ETD] –0.4% [95% CI –0.6, –0.3] [–5 mmol/mol (–6, –3)]; P < 0.0001). The treatment difference in HbA1c significantly favored oral semaglutide at week 26 for the trial product estimand (–1.4% vs. –0.9% [–15 vs. –9 mmol/mol], ETD –0.5% [95% CI –0.7, –0.4] [–6 mmol/mol (–7, –5)]; P < 0.0001) and at week 52 for both estimands (P < 0.0001). Superior weight loss was not confirmed at week 26 (treatment policy), but oral semaglutide was significantly better than empagliflozin at week 52 (trial product −4.7 vs. −3.8 kg; P = 0.0114). Gastrointestinal adverse events were more common with oral semaglutide. CONCLUSIONS Oral semaglutide was superior to empagliflozin in reducing HbA1c but not body weight at 26 weeks in patients with type 2 diabetes uncontrolled on metformin. At week 52, HbA1c and body weight (trial product estimand) were significantly reduced versus empagliflozin. Oral semaglutide was well tolerated within the established safety profile of GLP-1 receptor agonists.

yearjournalcountryeditionlanguage
2019-01-01
10.2337/dc19-0883https://doi.org/10.2337/dc19-0883