PMID- 20380656 OWN - NLM STAT- MEDLINE DCOM- 20110328 LR - 20221207 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 12 IP - 4 DP - 2010 Apr TI - Dutogliptin, a selective DPP4 inhibitor, improves glycaemic control in patients with type 2 diabetes: a 12-week, double-blind, randomized, placebo-controlled, multicentre trial. PG - 348-55 LID - 10.1111/j.1463-1326.2010.01195.x [doi] AB - AIM: To determine efficacy and tolerability of dutogliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor, in patients with type 2 diabetes mellitus. METHODS: This was a 12-week, multicentre, randomized, double-blind, placebo-controlled trial in 423 patients with type 2 diabetes with suboptimal metabolic control. Following a 2-week single-blind placebo run-in, patients aged 18-75 years with a body mass index of 25-48 kg/m(2) and baseline HbA1c of 7.3-11.0% were randomized 2:2:1 to receive once-daily oral therapy with either dutogliptin (400 or 200 mg) or placebo on a background medication of either metformin alone, a thiazolidinedione (TZD) alone or a combination of metformin plus a TZD. RESULTS: Average HbA1c at baseline was 8.4%. Administration of dutogliptin 400 and 200 mg for 12 weeks decreased HbA1c by -0.52% (p < 0.001) and -0.35% (p = 0.006), respectively (placebo-corrected values), with absolute changes in HbA1c for the 400 mg, 200 mg and placebo groups of -0.82, -0.64 and -0.3%, respectively. The proportion of patients achieving an HbA1c < 7% was 27, 21 and 12% at dutogliptin doses of 400 and 200 mg or placebo, respectively (p = 0.008 for comparison of 400 mg vs. placebo). Fasting plasma glucose (FPG) levels were significantly reduced in both active treatment groups compared to placebo: the placebo-corrected difference was -1.00 mmol/l (p < 0.001) for the 400 mg group and -0.88 mmol/l (p = 0.003) for the 200 mg group. Dutogliptin caused significantly greater reductions in postprandial glucose AUC (0-2h) in both the 400 and 200 mg groups (placebo corrected values -2.58 mmol/l/h, p < 0.001 and -1.63 mmol/l/h, p = 0.032, respectively). In general, patients tolerated the study drug well. There were minor, not clinically meaningful differences in adverse events (AEs) between dutogliptin-treated patients and placebo controls, and 60% of all reported AEs were mild. Vital signs and body weight were stable, and routine safety laboratory parameters did not change compared with placebo. Trough ex vivo DPP4 inhibition at the end of the 12-week treatment period was 80 and 70%, at the 400 and 200 mg doses of dutogliptin, respectively. CONCLUSIONS: Dutogliptin treatment for 12 weeks improved glycaemic control in patients with type 2 diabetes who were on a background medication of metformin, a TZD or metformin plus a TZD. Tolerability was favourable for both doses tested. The 400 mg dose of dutogliptin resulted in larger changes of HbA1c and FPG and more subjects reached an HbA1c target of < 7% than the 200 mg dose. FAU - Pattzi, H M R AU - Pattzi HM AD - Instituto Mexicano de Investigaciones Clinicas, Mexico City, Mexico. FAU - Pitale, S AU - Pitale S FAU - Alpizar, M AU - Alpizar M FAU - Bennett, C AU - Bennett C FAU - O'Farrell, A M AU - O'Farrell AM FAU - Li, J AU - Li J FAU - Cherrington, J M AU - Cherrington JM FAU - Guler, H-P AU - Guler HP CN - PHX1149-PROT202 Study 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 (Boronic Acids) RN - 0 (Glycated Hemoglobin A) RN - 0 (Hypoglycemic Agents) RN - 0 (Placebos) RN - 38EAO245ZX (dutogliptin) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Boronic Acids/*administration & dosage MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Glycated Hemoglobin/*metabolism MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Male MH - Middle Aged MH - Placebos MH - Treatment Outcome MH - Young Adult FIR - Barreiro, Graciela IR - Barreiro G FIR - Comes, Ana Florencia IR - Comes AF FIR - Cuadrado, Jesus Abel IR - Cuadrado JA FIR - Cuneo, Carlos Alberto IR - Cuneo CA FIR - Diaz, Monica IR - Diaz M FIR - Hermida, Sonia IR - Hermida S FIR - Jure, Horacio IR - Jure H FIR - Lapertosa, Silvia IR - Lapertosa S FIR - Maffei, Laura Elena IR - Maffei LE FIR - Man, Zulema IR - Man Z FIR - Massari, Fabio IR - Massari F FIR - Zaidman, Cesar Javier IR - Zaidman CJ FIR - Akhras, Ronald IR - Akhras R FIR - Bailey, Gordon R IR - Bailey GR FIR - Chilvers, Martyn IR - Chilvers M FIR - Dzongowski, Peter IR - Dzongowski P FIR - Hart, Randy IR - Hart R FIR - Kanani, Subodh IR - Kanani S FIR - Lai, James IR - Lai J FIR - Lasko, Ben IR - Lasko B FIR - Malette, Paul IR - Malette P FIR - O'Keefe, Dennis L IR - O'Keefe DL FIR - Ross, Stuart A IR - Ross SA FIR - Stewart, David I IR - Stewart DI FIR - Tellier, Guy IR - Tellier G FIR - Mahadevan, Shriraam IR - Mahadevan S FIR - Mutha, Abhay IR - Mutha A FIR - Patni, Rajeev IR - Patni R FIR - Pitale, Shailesh IR - Pitale S FIR - Rao, P V IR - Rao PV FIR - Sethi, B K IR - Sethi BK FIR - Shah, Parag IR - Shah P FIR - Thacker, Hemant IR - Thacker H FIR - Viswanathan, Vijay IR - Viswanathan V FIR - Salinas, Carlos Aguilar IR - Salinas CA FIR - Alpizar, Melchor IR - Alpizar M FIR - Carmona-Furusho, Luis-Kenji IR - Carmona-Furusho LK FIR - Carranza, Jaime IR - Carranza J FIR - Fanghanel, Guillermo IR - Fanghanel G FIR - Lozano, Fernando Flores IR - Lozano FF FIR - Pattzi, Hiromi Monika Rodriguez IR - Pattzi HM FIR - Gonzalez-Gonzalez, Gerardo IR - Gonzalez-Gonzalez G FIR - Gonzalez-Ortiz, Manuel IR - Gonzalez-Ortiz M FIR - Rodriguez, Eduardo Marquez IR - Rodriguez EM FIR - Rios, Esteban IR - Rios E FIR - Sanchez-Mijangos, Hector IR - Sanchez-Mijangos H FIR - Acampora, Matthew IR - Acampora M FIR - Adams, Michael R IR - Adams MR FIR - Adkins, Steve IR - Adkins S FIR - Agaiby, John Mounir IR - Agaiby JM FIR - Anastasi, Lawrence J IR - Anastasi LJ FIR - Argoud, Georges M IR - Argoud GM FIR - Banarer, Salomon IR - Banarer S FIR - Buettner, Craig Martin IR - Buettner CM FIR - Buth, Dennis K IR - Buth DK FIR - Chappel, Christopher M IR - Chappel CM FIR - Cheung, Deanna G IR - Cheung DG FIR - Clower, James W 3rd IR - Clower JW 3rd FIR - Cohen, Lisa M IR - Cohen LM FIR - Corder, Clinton N IR - Corder CN FIR - Doris, James F IR - Doris JF FIR - Downey, H Jackson IR - Downey HJ FIR - Duckor, Steven IR - Duckor S FIR - Ellison, William Travis IR - Ellison WT FIR - Fidelholtz, James I IR - Fidelholtz JI FIR - First, Brian P IR - First BP FIR - Forker, Alan IR - Forker A FIR - Gilbert, John M Jr IR - Gilbert JM Jr FIR - Gottschlich, Gregory IR - Gottschlich G FIR - Greco, Susan N IR - Greco SN FIR - Hassman, Michael A IR - Hassman MA FIR - Herrod, Herrod IR - Herrod H FIR - Horowitz, Barry S IR - Horowitz BS FIR - Jones, Conigliaro IR - Jones C FIR - Jones, SpencerB IR - Jones S FIR - Kerwin, Edward M IR - Kerwin EM FIR - Khronusova, Yekaterina IR - Khronusova Y FIR - Koren, Michael J IR - Koren MJ FIR - Kotek, Larry W IR - Kotek LW FIR - Levinson, Lawrence S IR - Levinson LS FIR - Littlejohn, Thomas W 3rd IR - Littlejohn TW 3rd FIR - Long, William J Jr IR - Long WJ Jr FIR - Lubin, Barry C IR - Lubin BC FIR - Meli, James V IR - Meli JV FIR - Mohan, Madhu IR - Mohan M FIR - Moll, David C IR - Moll DC FIR - Neutel, Joel Michael IR - Neutel JM FIR - Palmer, Samuel E IR - Palmer SE FIR - Pipek, Ruben IR - Pipek R FIR - Popeil, Larry R IR - Popeil LR FIR - Reeves, Matthew S IR - Reeves MS FIR - Rohlf, Jane IR - Rohlf J FIR - Roth, Eli M IR - Roth EM FIR - Schwartz, Sherwyn L IR - Schwartz SL FIR - Shepard, Marc R IR - Shepard MR FIR - Topkis, Robert L IR - Topkis RL EDAT- 2010/04/13 06:00 MHDA- 2011/03/29 06:00 CRDT- 2010/04/13 06:00 PHST- 2010/04/13 06:00 [entrez] PHST- 2010/04/13 06:00 [pubmed] PHST- 2011/03/29 06:00 [medline] AID - DOM1195 [pii] AID - 10.1111/j.1463-1326.2010.01195.x [doi] PST - ppublish SO - Diabetes Obes Metab. 2010 Apr;12(4):348-55. doi: 10.1111/j.1463-1326.2010.01195.x.