Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy

Richard E. Pratley, M. S. Kipnes, P. R. Fleck, C. Wilson, Q. Mekki, P. Castano, J. Cuadrado, L. Maffei, F. Massari, G. Sposetti, M. Ulla, S. Colagiuri, M. dEmden, D. O'Neal, J. Prins, A. Roberts, M. Dinato, A. Forti, J. Gross, C. Hayashida & 96 others J. Neto, R. Rea, L. Aguirre, G. Gonzalo, F. Munizaga, F. Luna-Sevez, A. Granandos-Fuentes, L. Ramirez-Roca, F. Sanchez-Morales, K. Prasanna Kumar, N. Rais, V. Seshiah, N. Thomas, M. Viswanathan, V. Viswanathan, C. Dueñas-Garcia, G. Gonzalez-Galvez, C. Gonzalez-Villalpando, F. Mar-Arevalo, E. Morales-Villegas, F. Salinas-Gonzalez, A. Dees, A. Deijl, A. Dissanayake, J. Krebs, R. Scott, S. Young, H. Arbañil, S. Corigliano, L. Gonzales, A. Luna, G. Molina, L. More, J. Kuleta, J. Loba, P. Mader, A. Mikolajczyk-Swatko, J. Sawer-Szewczyk, A. Stankiewicz, Z. Stepien, W. Boyd, L. Burgess, G. Ellis, P. Joshi, L. De Teresa, T. Hall, C. McKinnon, J. Ryan, J. Barrera, G. Bonabi, C. Chappel, W. Cheatham, L. Cohen, C. Corder, S. Elliott, D. Fitz-Patrick, M. Hassman, P. Hollander, D. Hurley, C. Jones, M. Kipnes, W. Koppel, S. Landgarten, A. Lewin, M. Lindley, R. Lipetz, T. Littlejohn, J. Lucas, G. Mark, R. Marple, E. Mattson, S. Mayeda, M. McAdoo, D. Morin, J. Mullen, J. Neutel, P. Norwood, S. Oates, A. Odugbesan, R. Pratley, K. Pudi, M. Rendell, K. Rock, J. Rosenstock, K. Sall, D. Santram, M. Seidner, T. Smith, M. Soboeiro, J. Sparks, R. Stegemoller, L. Taber, H. Wadsworth, J. Wahle, R. Weinstein, J. Wilker

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

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, β-cell function (fasting proinsulin, insulin, proinsulin/insulin ratio, and C-peptide, and homeostasis model assessment β-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 ≤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 ≥0.5% from baseline compared with patients in the placebo group (26.3%; p <0.001). Minor improvements in individual markers of β-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 12.5mg 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.

Original languageEnglish
Pages (from-to)167-176
Number of pages10
JournalDiabetes, Obesity and Metabolism
Volume11
Issue number2
DOIs
StatePublished - 2009
Externally publishedYes

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Dipeptidyl-Peptidase IV Inhibitors
Glyburide
Type 2 Diabetes Mellitus
Safety
Placebos
Proinsulin
Least-Squares Analysis
Hypoglycemia
alogliptin
Fasting
Insulin
Body Weight Changes
Vital Signs
C-Peptide
Incidence
Glycosylated Hemoglobin A
Therapeutics
Plasma Cells

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy. / Pratley, Richard E.; Kipnes, M. S.; Fleck, P. R.; Wilson, C.; Mekki, Q.; Castano, P.; Cuadrado, J.; Maffei, L.; Massari, F.; Sposetti, G.; Ulla, M.; Colagiuri, S.; dEmden, M.; O'Neal, D.; Prins, J.; Roberts, A.; Dinato, M.; Forti, A.; Gross, J.; Hayashida, C.; Neto, J.; Rea, R.; Aguirre, L.; Gonzalo, G.; Munizaga, F.; Luna-Sevez, F.; Granandos-Fuentes, A.; Ramirez-Roca, L.; Sanchez-Morales, F.; Prasanna Kumar, K.; Rais, N.; Seshiah, V.; Thomas, N.; Viswanathan, M.; Viswanathan, V.; Dueñas-Garcia, C.; Gonzalez-Galvez, G.; Gonzalez-Villalpando, C.; Mar-Arevalo, F.; Morales-Villegas, E.; Salinas-Gonzalez, F.; Dees, A.; Deijl, A.; Dissanayake, A.; Krebs, J.; Scott, R.; Young, S.; Arbañil, H.; Corigliano, S.; Gonzales, L.; Luna, A.; Molina, G.; More, L.; Kuleta, J.; Loba, J.; Mader, P.; Mikolajczyk-Swatko, A.; Sawer-Szewczyk, J.; Stankiewicz, A.; Stepien, Z.; Boyd, W.; Burgess, L.; Ellis, G.; Joshi, P.; De Teresa, L.; Hall, T.; McKinnon, C.; Ryan, J.; Barrera, J.; Bonabi, G.; Chappel, C.; Cheatham, W.; Cohen, L.; Corder, C.; Elliott, S.; Fitz-Patrick, D.; Hassman, M.; Hollander, P.; Hurley, D.; Jones, C.; Kipnes, M.; Koppel, W.; Landgarten, S.; Lewin, A.; Lindley, M.; Lipetz, R.; Littlejohn, T.; Lucas, J.; Mark, G.; Marple, R.; Mattson, E.; Mayeda, S.; McAdoo, M.; Morin, D.; Mullen, J.; Neutel, J.; Norwood, P.; Oates, S.; Odugbesan, A.; Pratley, R.; Pudi, K.; Rendell, M.; Rock, K.; Rosenstock, J.; Sall, K.; Santram, D.; Seidner, M.; Smith, T.; Soboeiro, M.; Sparks, J.; Stegemoller, R.; Taber, L.; Wadsworth, H.; Wahle, J.; Weinstein, R.; Wilker, J.

In: Diabetes, Obesity and Metabolism, Vol. 11, No. 2, 2009, p. 167-176.

Research output: Contribution to journalArticle

Pratley, RE, Kipnes, MS, Fleck, PR, Wilson, C, Mekki, Q, Castano, P, Cuadrado, J, Maffei, L, Massari, F, Sposetti, G, Ulla, M, Colagiuri, S, dEmden, M, O'Neal, D, Prins, J, Roberts, A, Dinato, M, Forti, A, Gross, J, Hayashida, C, Neto, J, Rea, R, Aguirre, L, Gonzalo, G, Munizaga, F, Luna-Sevez, F, Granandos-Fuentes, A, Ramirez-Roca, L, Sanchez-Morales, F, Prasanna Kumar, K, Rais, N, Seshiah, V, Thomas, N, Viswanathan, M, Viswanathan, V, Dueñas-Garcia, C, Gonzalez-Galvez, G, Gonzalez-Villalpando, C, Mar-Arevalo, F, Morales-Villegas, E, Salinas-Gonzalez, F, Dees, A, Deijl, A, Dissanayake, A, Krebs, J, Scott, R, Young, S, Arbañil, H, Corigliano, S, Gonzales, L, Luna, A, Molina, G, More, L, Kuleta, J, Loba, J, Mader, P, Mikolajczyk-Swatko, A, Sawer-Szewczyk, J, Stankiewicz, A, Stepien, Z, Boyd, W, Burgess, L, Ellis, G, Joshi, P, De Teresa, L, Hall, T, McKinnon, C, Ryan, J, Barrera, J, Bonabi, G, Chappel, C, Cheatham, W, Cohen, L, Corder, C, Elliott, S, Fitz-Patrick, D, Hassman, M, Hollander, P, Hurley, D, Jones, C, Kipnes, M, Koppel, W, Landgarten, S, Lewin, A, Lindley, M, Lipetz, R, Littlejohn, T, Lucas, J, Mark, G, Marple, R, Mattson, E, Mayeda, S, McAdoo, M, Morin, D, Mullen, J, Neutel, J, Norwood, P, Oates, S, Odugbesan, A, Pratley, R, Pudi, K, Rendell, M, Rock, K, Rosenstock, J, Sall, K, Santram, D, Seidner, M, Smith, T, Soboeiro, M, Sparks, J, Stegemoller, R, Taber, L, Wadsworth, H, Wahle, J, Weinstein, R & Wilker, J 2009, 'Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy', Diabetes, Obesity and Metabolism, vol. 11, no. 2, pp. 167-176. https://doi.org/10.1111/j.1463-1326.2008.01016.x
Pratley, Richard E. ; Kipnes, M. S. ; Fleck, P. R. ; Wilson, C. ; Mekki, Q. ; Castano, P. ; Cuadrado, J. ; Maffei, L. ; Massari, F. ; Sposetti, G. ; Ulla, M. ; Colagiuri, S. ; dEmden, M. ; O'Neal, D. ; Prins, J. ; Roberts, A. ; Dinato, M. ; Forti, A. ; Gross, J. ; Hayashida, C. ; Neto, J. ; Rea, R. ; Aguirre, L. ; Gonzalo, G. ; Munizaga, F. ; Luna-Sevez, F. ; Granandos-Fuentes, A. ; Ramirez-Roca, L. ; Sanchez-Morales, F. ; Prasanna Kumar, K. ; Rais, N. ; Seshiah, V. ; Thomas, N. ; Viswanathan, M. ; Viswanathan, V. ; Dueñas-Garcia, C. ; Gonzalez-Galvez, G. ; Gonzalez-Villalpando, C. ; Mar-Arevalo, F. ; Morales-Villegas, E. ; Salinas-Gonzalez, F. ; Dees, A. ; Deijl, A. ; Dissanayake, A. ; Krebs, J. ; Scott, R. ; Young, S. ; Arbañil, H. ; Corigliano, S. ; Gonzales, L. ; Luna, A. ; Molina, G. ; More, L. ; Kuleta, J. ; Loba, J. ; Mader, P. ; Mikolajczyk-Swatko, A. ; Sawer-Szewczyk, J. ; Stankiewicz, A. ; Stepien, Z. ; Boyd, W. ; Burgess, L. ; Ellis, G. ; Joshi, P. ; De Teresa, L. ; Hall, T. ; McKinnon, C. ; Ryan, J. ; Barrera, J. ; Bonabi, G. ; Chappel, C. ; Cheatham, W. ; Cohen, L. ; Corder, C. ; Elliott, S. ; Fitz-Patrick, D. ; Hassman, M. ; Hollander, P. ; Hurley, D. ; Jones, C. ; Kipnes, M. ; Koppel, W. ; Landgarten, S. ; Lewin, A. ; Lindley, M. ; Lipetz, R. ; Littlejohn, T. ; Lucas, J. ; Mark, G. ; Marple, R. ; Mattson, E. ; Mayeda, S. ; McAdoo, M. ; Morin, D. ; Mullen, J. ; Neutel, J. ; Norwood, P. ; Oates, S. ; Odugbesan, A. ; Pratley, R. ; Pudi, K. ; Rendell, M. ; Rock, K. ; Rosenstock, J. ; Sall, K. ; Santram, D. ; Seidner, M. ; Smith, T. ; Soboeiro, M. ; Sparks, J. ; Stegemoller, R. ; Taber, L. ; Wadsworth, H. ; Wahle, J. ; Weinstein, R. ; Wilker, J. / Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy. In: Diabetes, Obesity and Metabolism. 2009 ; Vol. 11, No. 2. pp. 167-176.
@article{7dc0e5702ece486c8d5523431ff8fa31,
title = "Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy",
abstract = "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, β-cell function (fasting proinsulin, insulin, proinsulin/insulin ratio, and C-peptide, and homeostasis model assessment β-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 ≤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 ≥0.5{\%} from baseline compared with patients in the placebo group (26.3{\%}; p <0.001). Minor improvements in individual markers of β-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 12.5mg 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.",
author = "Pratley, {Richard E.} and Kipnes, {M. S.} and Fleck, {P. R.} and C. Wilson and Q. Mekki and P. Castano and J. Cuadrado and L. Maffei and F. Massari and G. Sposetti and M. Ulla and S. Colagiuri and M. dEmden and D. O'Neal and J. Prins and A. Roberts and M. Dinato and A. Forti and J. Gross and C. Hayashida and J. Neto and R. Rea and L. Aguirre and G. Gonzalo and F. Munizaga and F. Luna-Sevez and A. Granandos-Fuentes and L. Ramirez-Roca and F. Sanchez-Morales and {Prasanna Kumar}, K. and N. Rais and V. Seshiah and N. Thomas and M. Viswanathan and V. Viswanathan and C. Due{\~n}as-Garcia and G. Gonzalez-Galvez and C. Gonzalez-Villalpando and F. Mar-Arevalo and E. Morales-Villegas and F. Salinas-Gonzalez and A. Dees and A. Deijl and A. Dissanayake and J. Krebs and R. Scott and S. Young and H. Arba{\~n}il and S. Corigliano and L. Gonzales and A. Luna and G. Molina and L. More and J. Kuleta and J. Loba and P. Mader and A. Mikolajczyk-Swatko and J. Sawer-Szewczyk and A. Stankiewicz and Z. Stepien and W. Boyd and L. Burgess and G. Ellis and P. Joshi and {De Teresa}, L. and T. Hall and C. McKinnon and J. Ryan and J. Barrera and G. Bonabi and C. Chappel and W. Cheatham and L. Cohen and C. Corder and S. Elliott and D. Fitz-Patrick and M. Hassman and P. Hollander and D. Hurley and C. Jones and M. Kipnes and W. Koppel and S. Landgarten and A. Lewin and M. Lindley and R. Lipetz and T. Littlejohn and J. Lucas and G. Mark and R. Marple and E. Mattson and S. Mayeda and M. McAdoo and D. Morin and J. Mullen and J. Neutel and P. Norwood and S. Oates and A. Odugbesan and R. Pratley and K. Pudi and M. Rendell and K. Rock and J. Rosenstock and K. Sall and D. Santram and M. Seidner and T. Smith and M. Soboeiro and J. Sparks and R. Stegemoller and L. Taber and H. Wadsworth and J. Wahle and R. Weinstein and J. Wilker",
year = "2009",
doi = "10.1111/j.1463-1326.2008.01016.x",
language = "English",
volume = "11",
pages = "167--176",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy

AU - Pratley, Richard E.

AU - Kipnes, M. S.

AU - Fleck, P. R.

AU - Wilson, C.

AU - Mekki, Q.

AU - Castano, P.

AU - Cuadrado, J.

AU - Maffei, L.

AU - Massari, F.

AU - Sposetti, G.

AU - Ulla, M.

AU - Colagiuri, S.

AU - dEmden, M.

AU - O'Neal, D.

AU - Prins, J.

AU - Roberts, A.

AU - Dinato, M.

AU - Forti, A.

AU - Gross, J.

AU - Hayashida, C.

AU - Neto, J.

AU - Rea, R.

AU - Aguirre, L.

AU - Gonzalo, G.

AU - Munizaga, F.

AU - Luna-Sevez, F.

AU - Granandos-Fuentes, A.

AU - Ramirez-Roca, L.

AU - Sanchez-Morales, F.

AU - Prasanna Kumar, K.

AU - Rais, N.

AU - Seshiah, V.

AU - Thomas, N.

AU - Viswanathan, M.

AU - Viswanathan, V.

AU - Dueñas-Garcia, C.

AU - Gonzalez-Galvez, G.

AU - Gonzalez-Villalpando, C.

AU - Mar-Arevalo, F.

AU - Morales-Villegas, E.

AU - Salinas-Gonzalez, F.

AU - Dees, A.

AU - Deijl, A.

AU - Dissanayake, A.

AU - Krebs, J.

AU - Scott, R.

AU - Young, S.

AU - Arbañil, H.

AU - Corigliano, S.

AU - Gonzales, L.

AU - Luna, A.

AU - Molina, G.

AU - More, L.

AU - Kuleta, J.

AU - Loba, J.

AU - Mader, P.

AU - Mikolajczyk-Swatko, A.

AU - Sawer-Szewczyk, J.

AU - Stankiewicz, A.

AU - Stepien, Z.

AU - Boyd, W.

AU - Burgess, L.

AU - Ellis, G.

AU - Joshi, P.

AU - De Teresa, L.

AU - Hall, T.

AU - McKinnon, C.

AU - Ryan, J.

AU - Barrera, J.

AU - Bonabi, G.

AU - Chappel, C.

AU - Cheatham, W.

AU - Cohen, L.

AU - Corder, C.

AU - Elliott, S.

AU - Fitz-Patrick, D.

AU - Hassman, M.

AU - Hollander, P.

AU - Hurley, D.

AU - Jones, C.

AU - Kipnes, M.

AU - Koppel, W.

AU - Landgarten, S.

AU - Lewin, A.

AU - Lindley, M.

AU - Lipetz, R.

AU - Littlejohn, T.

AU - Lucas, J.

AU - Mark, G.

AU - Marple, R.

AU - Mattson, E.

AU - Mayeda, S.

AU - McAdoo, M.

AU - Morin, D.

AU - Mullen, J.

AU - Neutel, J.

AU - Norwood, P.

AU - Oates, S.

AU - Odugbesan, A.

AU - Pratley, R.

AU - Pudi, K.

AU - Rendell, M.

AU - Rock, K.

AU - Rosenstock, J.

AU - Sall, K.

AU - Santram, D.

AU - Seidner, M.

AU - Smith, T.

AU - Soboeiro, M.

AU - Sparks, J.

AU - Stegemoller, R.

AU - Taber, L.

AU - Wadsworth, H.

AU - Wahle, J.

AU - Weinstein, R.

AU - Wilker, J.

PY - 2009

Y1 - 2009

N2 - 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, β-cell function (fasting proinsulin, insulin, proinsulin/insulin ratio, and C-peptide, and homeostasis model assessment β-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 ≤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 ≥0.5% from baseline compared with patients in the placebo group (26.3%; p <0.001). Minor improvements in individual markers of β-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 12.5mg 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.

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, β-cell function (fasting proinsulin, insulin, proinsulin/insulin ratio, and C-peptide, and homeostasis model assessment β-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 ≤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 ≥0.5% from baseline compared with patients in the placebo group (26.3%; p <0.001). Minor improvements in individual markers of β-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 12.5mg 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.

UR - http://www.scopus.com/inward/record.url?scp=58149335320&partnerID=8YFLogxK

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U2 - 10.1111/j.1463-1326.2008.01016.x

DO - 10.1111/j.1463-1326.2008.01016.x

M3 - Article

VL - 11

SP - 167

EP - 176

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 2

ER -