PMID- 22210563 OWN - NLM STAT- MEDLINE DCOM- 20120612 LR - 20220409 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 35 IP - 2 DP - 2012 Feb TI - Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4): a 26-week double-blind study. PG - 252-8 LID - 10.2337/dc11-1107 [doi] AB - OBJECTIVE: To test the safety and efficacy of exenatide once weekly (EQW) compared with metformin (MET), pioglitazone (PIO), and sitagliptin (SITA) over 26 weeks, in suboptimally treated (diet and exercise) drug-naive patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients were randomized to subcutaneous (SC) EQW 2.0 mg + oral placebo (n = 248), MET 2,000 mg/day + SC placebo (n = 246), PIO 45 mg/day + SC placebo (n = 163), or SITA 100 mg/day + SC placebo (n = 163) for 26 weeks. MET and PIO therapies were increased to maximum-tolerated dosages. Injections with EQW or placebo were administered weekly, while oral medication or placebo was administered daily. RESULTS: Baseline characteristics were as follows: 59% men, 67% Caucasian, mean age 54 years, HbA(1c) 8.5%, fasting serum glucose 9.9 mmol/L, body weight 87.0 kg, and diabetes duration 2.7 years. HbA(1c) reductions (%) at 26 weeks (least-squares means) with EQW versus MET, PIO, and SITA were -1.53 vs. -1.48 (P = 0.620), -1.63 (P = 0.328), and -1.15 (P < 0.001), respectively. Weight changes (kg) were -2.0 vs. -2.0 (P = 0.892), +1.5 (P < 0.001), and -0.8 (P < 0.001), respectively. Common adverse events were as follows: EQW, nausea (11.3%) and diarrhea (10.9%); MET, diarrhea (12.6%) and headache (12.2%); PIO, nasopharyngitis (8.6%) and headache (8.0%); and SIT, nasopharyngitis (9.8%) and headache (9.2%). Minor (confirmed) hypoglycemia was rarely reported. No major hypoglycemia occurred. CONCLUSIONS: EQW was noninferior to MET but not PIO and superior to SITA with regard to HbA(1c) reduction at 26 weeks. Of the agents studied, EQW and MET provided similar improvements in glycemic control along with the benefit of weight reduction and no increased risk of hypoglycemia. FAU - Russell-Jones, David AU - Russell-Jones D AD - Department of Diabetes and Endocrinology, Royal Surrey County Hospital, University of Surrey, Guildford, UK. FAU - Cuddihy, Robert M AU - Cuddihy RM FAU - Hanefeld, Markolf AU - Hanefeld M FAU - Kumar, Ajay AU - Kumar A FAU - Gonzalez, Jose G AU - Gonzalez JG FAU - Chan, Melanie AU - Chan M FAU - Wolka, Anne M AU - Wolka AM FAU - Boardman, Marilyn K AU - Boardman MK CN - DURATION-4 Study Group LA - eng SI - ClinicalTrials.gov/NCT00676338 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20111230 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Hypoglycemic Agents) RN - 0 (Peptides) RN - 0 (Pyrazines) RN - 0 (Thiazolidinediones) RN - 0 (Triazoles) RN - 0 (Venoms) RN - 9100L32L2N (Metformin) RN - 9P1872D4OL (Exenatide) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - X4OV71U42S (Pioglitazone) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy MH - Double-Blind Method MH - Drug Administration Schedule MH - Exenatide MH - Female MH - Humans MH - Hypoglycemic Agents/administration & dosage/*therapeutic use MH - Male MH - Metformin/administration & dosage/*therapeutic use MH - Middle Aged MH - Peptides/administration & dosage/*therapeutic use MH - Pioglitazone MH - Pyrazines/administration & dosage/*therapeutic use MH - Sitagliptin Phosphate MH - Thiazolidinediones/administration & dosage/*therapeutic use MH - Treatment Outcome MH - Triazoles/administration & dosage/*therapeutic use MH - Venoms/administration & dosage/*therapeutic use PMC - PMC3263915 FIR - Massari, Fabio IR - Massari F FIR - Sposetti, Georgina IR - Sposetti G FIR - Maffei, Laura IR - Maffei L FIR - Starosiliz, David IR - Starosiliz D FIR - Goycoa, Claudia IR - Goycoa C FIR - Perez Mangui, Federico IR - Perez Mangui F FIR - Chertkoff, Alejandro IR - Chertkoff A FIR - Salzberg, Susana IR - Salzberg S FIR - Mathieu, Chantal IR - Mathieu C FIR - Timmermans, Bruno IR - Timmermans B FIR - Quintens, Theo IR - Quintens T FIR - Reynders, Paul IR - Reynders P FIR - Canani, Luis Henrique IR - Canani LH FIR - Forti, Adriana IR - Forti A FIR - Chacra, Antonio IR - Chacra A FIR - Geloneze, Bruno IR - Geloneze B FIR - 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Nowakowski A FIR - Jarosz-skokowska, Ewa IR - Jarosz-skokowska E FIR - Stasinska, Teresa IR - Stasinska T FIR - Gromniak, Elwira IR - Gromniak E FIR - Popa, Amorin IR - Popa A FIR - Ciomos, Daniela IR - Ciomos D FIR - Mistodie, Cristina IR - Mistodie C FIR - Vorobiev, Sergey IR - Vorobiev S FIR - Arefieva, Elena IR - Arefieva E FIR - Pronin, Vyatcheslav IR - Pronin V FIR - Miroshnichenko, Olga IR - Miroshnichenko O FIR - Ivanova, Svetlana IR - Ivanova S FIR - Dvoryashina, Irina IR - Dvoryashina I FIR - Zhavoronkova, Natalia IR - Zhavoronkova N FIR - Slavitskaya, Elena IR - Slavitskaya E FIR - Alpenidze, Diana IR - Alpenidze D FIR - Ilavska, Adriana IR - Ilavska A FIR - Duda, Jozef IR - Duda J FIR - Coetzer, Thomas IR - Coetzer T FIR - Wing, Jeffrey IR - Wing J FIR - Bhana, Sindeep IR - Bhana S FIR - Jacovides, Andrew IR - Jacovides A FIR - Duran Garcia, Santiago IR - Duran Garcia S FIR - Vazquez Martinez, Clotilde IR - Vazquez Martinez C FIR - Gonzalbez Morgaez, Jose IR - Gonzalbez Morgaez J FIR - De Teresa, Luis IR - De Teresa L FIR - Ma, Wen-ya IR - Ma WY FIR - Huang, Chien-ning IR - Huang CN FIR - Wang, Tzu-yuan IR - Wang TY FIR - Hsieh, An-tsz IR - Hsieh AT FIR - Altuntas, Yuksel IR - Altuntas Y FIR - Stephens, Jeffrey IR - Stephens J FIR - Russell-Jones, David IR - Russell-Jones D FIR - Atkin, Stephen IR - Atkin S FIR - Barnett, Anthony IR - Barnett A FIR - Cahill, Thomas IR - Cahill T FIR - Frier, Brian IR - Frier B FIR - Adelizzi, Angela IR - Adelizzi A FIR - Miller, Jeffrey IR - Miller J FIR - Blevins, Thomas IR - Blevins T FIR - Greco, Susan IR - Greco S FIR - Brown, Morris IR - Brown M FIR - Butuk, David IR - Butuk D FIR - Comulada Rivera, Angel IR - Comulada Rivera A FIR - Cuddihy, Robert IR - Cuddihy R FIR - Guice, Michael IR - Guice M FIR - Harris, Ronald IR - Harris R FIR - Herring, Charles IR - Herring C FIR - Jacks, Randal IR - Jacks R FIR - Kennedy, John IR - Kennedy J FIR - Severa, Larry IR - Severa L FIR - Ortiz-Carrasquillo, Ramon IR - Ortiz-Carrasquillo R FIR - Pin, Michael IR - Pin M FIR - Rovner, Sergio IR - Rovner S FIR - Samson, Mercedes IR - Samson M FIR - Bhargava, Anuj IR - Bhargava A EDAT- 2012/01/03 06:00 MHDA- 2012/06/13 06:00 PMCR- 2013/02/01 CRDT- 2012/01/03 06:00 PHST- 2012/01/03 06:00 [entrez] PHST- 2012/01/03 06:00 [pubmed] PHST- 2012/06/13 06:00 [medline] PHST- 2013/02/01 00:00 [pmc-release] AID - dc11-1107 [pii] AID - 1107 [pii] AID - 10.2337/dc11-1107 [doi] PST - ppublish SO - Diabetes Care. 2012 Feb;35(2):252-8. doi: 10.2337/dc11-1107. Epub 2011 Dec 30.