PMID- 19125778 OWN - NLM STAT- MEDLINE DCOM- 20090805 LR - 20221207 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 11 IP - 2 DP - 2009 Feb TI - Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy. PG - 167-76 LID - 10.1111/j.1463-1326.2008.01016.x [doi] AB - AIM: To evaluate the efficacy and safety of alogliptin, a potent and highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, in combination with glyburide in patients with type 2 diabetes inadequately controlled by sulphonylurea monotherapy. METHODS: After a 2-week screening period, adult patients 18-80 years of age entered a 4-week run-in/stabilization period in which they were switched from their own sulphonylurea medication to an equivalent dose of glyburide (open label) plus placebo (single blind). After the run-in period, patients were randomly assigned to double-blind treatment with alogliptin 12.5 mg (n = 203), alogliptin 25 mg (n = 198), or placebo (n = 99) for 26 weeks. The primary end-point was change from baseline to week 26 in glycosylated haemoglobin (HbA1c). Secondary end-points included clinical response rates and changes in fasting plasma glucose, beta-cell function (fasting proinsulin, insulin, proinsulin/insulin ratio, and C-peptide, and homeostasis model assessment beta-cell function), body weight, and safety end-points [adverse events (AEs), clinical laboratory tests, vital signs and electrocardiographic readings]. RESULTS: The study population had a mean age of 57 years and a mean disease duration of 8 years; it was well balanced for gender (52% women) and was mainly white (71%). The mean baseline HbA1c was approximately 8.1% in each group. Significantly greater least squares (LS) mean reductions in HbA1c were seen at week 26 with alogliptin 12.5 mg (-0.38%) and 25 mg (-0.52%) vs. placebo (+0.01%; p < 0.001), and more patients in the alogliptin 25-mg group had HbA1c levels < or =7.0% at week 26 (34.8%, p = 0.002) vs. placebo (18.2%). Proportionately more patients in the alogliptin 12.5 mg (47.3%) and 25 mg (50.5%) groups had an HbA1c reduction > or =0.5% from baseline compared with patients in the placebo group (26.3%; p < 0.001). Minor improvements in individual markers of beta-cell function were seen with alogliptin, but no significant treatment group differences were noted relative to placebo. Minor LS mean changes in body weight were noted across groups (placebo, -0.20 kg; alogliptin 12.5 mg, +0.60 kg; alogliptin 25 mg, +0.68 kg). AEs were reported for 63-64% of patients receiving alogliptin and 54% of patients receiving placebo. Few AEs were treatment limiting (2.0-2.5% across groups), and serious AEs (2.0-5.6%) were infrequent, similar across groups, and generally considered not related to treatment. The incidences of hypoglycaemia for placebo, alogliptin 12.5 mg and alogliptin 25 mg groups were 11.1, 15.8 and 9.6% respectively. CONCLUSIONS: In patients with type 2 diabetes inadequately controlled by glyburide monotherapy, the addition of alogliptin resulted in clinically significant reductions in HbA1c without increased incidence of hypoglycaemia. FAU - Pratley, R E AU - Pratley RE AD - Diabetes and Metabolism Translational Medicine Unit, University of Vermont College of Medicine, Burlington, VT 05446, USA. richard.pratley@uvm.edu FAU - Kipnes, M S AU - Kipnes MS FAU - Fleck, P R AU - Fleck PR FAU - Wilson, C AU - Wilson C FAU - Mekki, Q AU - Mekki Q CN - Alogliptin Study 007 Group LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin A) RN - 0 (Hypoglycemic Agents) RN - 0 (Piperidines) RN - 0 (Sulfonylurea Compounds) RN - 56HH86ZVCT (Uracil) RN - JHC049LO86 (alogliptin) RN - SX6K58TVWC (Glyburide) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - Glyburide/adverse effects/therapeutic use MH - Glycated Hemoglobin/metabolism MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Male MH - Middle Aged MH - Piperidines/adverse effects/*therapeutic use MH - Sulfonylurea Compounds/therapeutic use MH - Uracil/adverse effects/*analogs & derivatives/therapeutic use MH - Young Adult FIR - Castano, P IR - Castano P FIR - Cuadrado, J IR - Cuadrado J FIR - Maffei, L IR - Maffei L FIR - Massari, F IR - Massari F FIR - Sposetti, G IR - Sposetti G FIR - Ulla, M IR - Ulla M FIR - Colagiuri, S IR - Colagiuri S FIR - dEmden, M IR - dEmden M FIR - O'Neal, D IR - O'Neal D FIR - Prins, J IR - Prins J FIR - Roberts, A IR - Roberts A FIR - Dinato, M IR - Dinato M FIR - Forti, A IR - Forti A FIR - Gross, J IR - Gross J FIR - Hayashida, C IR - Hayashida C FIR - Neto, J IR - Neto J FIR - Rea, R IR - Rea R FIR - Aguirre, L IR - Aguirre L FIR - Gonzalo, G IR - Gonzalo G FIR - Munizaga, F IR - Munizaga F FIR - Luna-Sevez, F IR - Luna-Sevez F FIR - Granandos-Fuentes, A IR - Granandos-Fuentes A FIR - Ramirez-Roca, L IR - Ramirez-Roca L FIR - Sanchez-Morales, F IR - Sanchez-Morales F FIR - Prasanna Kumar, K IR - Prasanna Kumar K FIR - Rais, N IR - Rais N FIR - Seshiah, V IR - Seshiah V FIR - Thomas, N IR - Thomas N FIR - Viswanathan, M IR - Viswanathan M FIR - Viswanathan, V IR - Viswanathan V FIR - Duenas-Garcia, C IR - Duenas-Garcia C FIR - Gonzalez-Galvez, G IR - Gonzalez-Galvez G FIR - Gonzalez-Villalpando, C IR - Gonzalez-Villalpando C FIR - Mar-Arevalo, F IR - Mar-Arevalo F FIR - Morales-Villegas, E IR - Morales-Villegas E FIR - Salinas-Gonzalez, F IR - Salinas-Gonzalez F FIR - Dees, A IR - Dees A FIR - Deijl, A IR - Deijl A FIR - Dissanayake, A IR - Dissanayake A FIR - Krebs, J IR - Krebs J FIR - Scott, R IR - Scott R FIR - Young, S IR - Young S FIR - Arbanil, H IR - Arbanil H FIR - Corigliano, S IR - Corigliano S FIR - Gonzales, L IR - Gonzales L FIR - Luna, A IR - Luna A FIR - Molina, G IR - Molina G FIR - More, L IR - More L FIR - Kuleta, J IR - Kuleta J FIR - Loba, J IR - Loba J FIR - Mader, P IR - Mader P FIR - Mikolajczyk-Swatko, A IR - Mikolajczyk-Swatko A FIR - Sawer-Szewczyk, J IR - Sawer-Szewczyk J FIR - Stankiewicz, A IR - Stankiewicz A FIR - Stepien, A IR - Stepien A FIR - Boyd, W IR - Boyd W FIR - Burgess, L IR - Burgess L FIR - Ellis, G IR - Ellis G FIR - Joshi, P IR - Joshi P FIR - De Teresa, L IR - De Teresa L FIR - Hall, T IR - Hall T FIR - McKinnon, C IR - McKinnon C FIR - Ryan, J IR - Ryan J FIR - Barrera, J IR - Barrera J FIR - Bonabi, G IR - Bonabi G FIR - Chappel, C IR - Chappel C FIR - Cheatham, W IR - Cheatham W FIR - Cohen, L IR - Cohen L FIR - Corder, C IR - Corder C FIR - Elliott, S IR - Elliott S FIR - Fitz-Patrick, D IR - Fitz-Patrick D FIR - Hassman, M IR - Hassman M FIR - Hollander, P IR - Hollander P FIR - Hurley, D IR - Hurley D FIR - Jones, C IR - Jones C FIR - Kipnes, M IR - Kipnes M FIR - Koppel, W IR - Koppel W FIR - Landgarten, S IR - Landgarten S FIR - Lewin, A IR - Lewin A FIR - Lindley, M IR - Lindley M FIR - Lipetz, R IR - Lipetz R FIR - Littlejohn, T IR - Littlejohn T FIR - Lucas, J IR - Lucas J FIR - Mark, G IR - Mark G FIR - Marple, R IR - Marple R FIR - Mattson, E IR - Mattson E FIR - Mayeda, S IR - Mayeda S FIR - McAdoo, M IR - McAdoo M FIR - Morin, D IR - Morin D FIR - Mullen, J IR - Mullen J FIR - Neutel, J IR - Neutel J FIR - Norwood, P IR - Norwood P FIR - Oates, S IR - Oates S FIR - Odugbesan, A IR - Odugbesan A FIR - Phillips, F IR - Phillips F FIR - Pratley, R IR - Pratley R FIR - Pudi, K IR - Pudi K FIR - Rendell, M IR - Rendell M FIR - Rock, K IR - Rock K FIR - Rosenstock, J IR - Rosenstock J FIR - Sall, K IR - Sall K FIR - Santram, D IR - Santram D FIR - Seidner, M IR - Seidner M FIR - Smith, T IR - Smith T FIR - Soboeiro, M IR - Soboeiro M FIR - Sparks, J IR - Sparks J FIR - Stegemoller, R IR - Stegemoller R FIR - Taber, L IR - Taber L FIR - Wadsworth, H IR - Wadsworth H FIR - Wahle, J IR - Wahle J FIR - Weinstein, R IR - Weinstein R FIR - Wilker, J IR - Wilker J EDAT- 2009/01/08 09:00 MHDA- 2009/08/06 09:00 CRDT- 2009/01/08 09:00 PHST- 2009/01/08 09:00 [entrez] PHST- 2009/01/08 09:00 [pubmed] PHST- 2009/08/06 09:00 [medline] AID - DOM1016 [pii] AID - 10.1111/j.1463-1326.2008.01016.x [doi] PST - ppublish SO - Diabetes Obes Metab. 2009 Feb;11(2):167-76. doi: 10.1111/j.1463-1326.2008.01016.x.