Efficacy of alogliptin in type 2 diabetes treatment: a meta-analysis of randomized double-blind controlled studies

BMC Endocrine Disorders

Yifru Berhan¹  Asres Berhan¹ 

[1] Hawassa University College of Medicine and Health Sciences, Hawassa University, P. O. Box: 1560, Hawassa, Ethiopia

关键词: Type 2 diabetes;    Meta-analysis;    HbA1c;    FPG;    DPP-4 inhibitors;    Body weight;    Alogliptin;   

Others  :  1085950
DOI  :  10.1186/1472-6823-13-9

 received in 2012-09-19, accepted in 2013-02-27,  发布年份 2013

【 摘 要 】

Background

Alogliptin is a new dipeptidyl peptidase (DPP-4) inhibitor, which is under investigation for treatment of type 2 diabetes either alone or in combination with other antidiabetic drugs. The aim of this meta-analysis was to assess the efficacy and tolerability of alogliptin in patients with type 2 diabetes.

Methods

Computer based search was performed in MEDLINE, Cochrane library, and HINARI (Health InterNetwork Access to Research Initiative) databases. Meta-analysis was carried out by incorporating double-blind randomized controlled studies done on the efficacy of alogliptin in patients with type 2 diabetes. The efficacy and tolerability of alogliptin was determined by standardized mean differences (SMDs) and Mantel-Haenszel odds ratio. Heterogeneity was assessed by the chi-squared test (Cochran Q test) and I² statistics.

Results

The pooled SMDs demonstrated a significant reduction in HbA1c in patients treated with alogliptin 12.5 mg (SMD = −0.81; 95% CI, -1.11 to −0.51) or alogliptin 25 mg (SMD= −0.98; 95%CI= −1.30 to −0.66) as compared with controls. The SMD for reduction in fasting plasma glucose level (FPG) from baseline was also statistically significant among alogliptin treated patients. However, the effect of alogliptin on body weight change was inconclusive. The proportion of patients who discontinued alogliptin due to adverse events was not different from controls. Similarly, the meta-analyses of specific adverse events did not demonstrate statistically significant differences.

Conclusions

Alogliptin alone or in combination with other antidiabetic drug has shown a significant reduction in HbA1c and FPG level in patients with type 2 diabetes. However, its consistent efficacy for longer duration of therapy needs further investigation.

【 授权许可】

   
2013 Berhan and Berhan; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Rosenstock J, Riddle MC: Insulin therapy in type 2 diabetes. In The CADRE handbook of diabetes management. Edited by Cefalu WT, Gerich JE, Leroith D. New York: Medical Information Press; 2004:145-168.
• [2]Chacra AR, Davidson JA, Diaz J, Escalante-Pulido M, Litwak LE, Mestman JH, More L, Violante RM: An algorithm for the treatment of type 2 diabetes in Latin America. Diabetes Obes Metab 2005, 7:148-160.
• [3]Holst JJ, Knop FK, Vilsbøll T, Krarup T, Madsbad S: Loss of incretin effect is a specific, important, and early characteristic of type 2 diabetes. Diabetes Care 2011, 34(Suppl2):S251-S257.
• [4]Drucker DJ: The role of gut hormones in glucose homeostasis. J Clin Invest 2007, 117:24-32.
• [5]Covington P, Christopher R, Davenport M, Fleck P, Mekki QA, Wann ER, Karim A: Pharmacokinetic, pharmacodynamic, and tolerability profiles of the dipeptidyl peptidase–4 inhibitor alogliptin: a randomized, double-blind, placebo-controlled, multiple-dose study in adult patients with type 2 diabetes. Clin Ther 2008, 30(3):499-512.
• [6]Christopher R, Covington P, Davenport M, Fleck P, Mekki QA, Wann ER, Karim A: Pharmacokinetics, pharmacodynamics, and tolerability of single increasing doses of the dipeptidyl peptidase–4 inhibitor alogliptin in healthy male subjects. Clin Ther 2008, 30(3):513-527.
• [7]Wilmington N.C. PPD, Inc. (Nasdaq: PPDI): PPD confirms Takeda receives NDA approval of NESINA® (alogliptin) from Japanese ministry of health, labour and welfare. Available from: http://files.shareholder.com/downloads/PPDI/ebec798d14b9/PPDI.pdf webcite
• [8]Insight Pharma reports: executive summary. Accessed in 2012. Available from: http://www.insightpharmareports.com/uploadedFiles/ExecutiveSummary webcite
• [9]Viereck C, Boudes P: An analysis of the impact of FDA's guidelines for addressing cardiovascular risk of drugs for type 2 diabetes on clinical development. Contemp Clin Trials 2011, 32(3):324-332.
• [10]Choe C, Edelman S: New therapeutic options for treating type-2 diabetes: a review of insulin analogs and premixed insulin analogs. J Natl Med Assoc 2007, 99(4):357-367.
• [11]GooBen K, Gra¨ber S: Longer term safety of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus: systematic review and meta-analysis. Diabetes Obes Metab 2012, 14(12):1061-1072.
• [12]Conversion of units of glucose plasmatic level. Accessed in 2012. Available from: http://en.mte.cz/conversion.php webcite
• [13]Rosenstock R, Rendell MS, Gross JL, Fleck PR, Wilson CA, Mekki Q: Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA1c without causing weight gain or increased hypoglycemia. Diabetes Obes Metab 2009, 11:1145-1152. Study 1
• [14]Sterne JAC, Sutton AJ, Ioannidis JPA, Terrin N, Jones DR, Lau J, Carpenter J, Rücker G, Harbord RM, Schmid CH, Tetzlaff J, Deeks JJ, Peters J, Macaskill P, Schwarzer G, Duva S, Altman DG, Moher D, Higgins JP: Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 2011, 342:d4002.
• [15]Moher D, Liberati A, Tetzlaff J, Altman DG, and the PRISMA Group: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009, 6(7):e1000097. Available from: http://medicine.plosjournals.org/ webcite
• [16]Review manager (RevMan) [computer program]. version 5.1. Copenhagen: the Nordic Cochrane centre, the Cochrane collaboration, 2011. Available from http://ims.cochrane.org/revman webcite
• [17]Borenstein M, Hedges L, Higgins J, Rothstein H: Comprehensive meta-analysis version 2. Englewood NJ: Biostat; 2005.
• [18]Bosi E, Ellis GC, Wilson CA, Fleck PR: Alogliptin as a third oral antidiabetic drug in patients with type 2 diabetes and inadequate glycaemic control on metformin and pioglitazone: a 52 week, randomized, double-blind, active-controlled, parallel-group study. Diabetes Obes Metab 2011, 13:1088-1096.
• [19]Nauck MA, Ellis GC, Fleck PR, Wilson CA, Mekki Q, and for the alogliptin Study 008 Group: Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomized, double-blind, placebo-controlled study. Int J Clin Pract 2009, 63(1):46-55.
• [20]Pratley RE, Reusch JEB, RWilson CA FP, Mekki Q: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Curr Med Res Opin 2009, 25(10):2361-2371. Study 1
• [21]Pratley RE, Kipnes MS, Fleck PR, Wilson C, Mekki Q: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapy. Diabetes Obes Metab 2009, 11:167-176. Study 2
• [22]Defronzo RA, Fleck PR, Wilson CA, Mekki Q: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes and inadequate glycemic control. Diabetes Care 2008, 31:2315-2317.
• [23]Rosenstock J, Inzucchi SE, Seufert J, Fleck PR, Wilson CA, Mekki Q: Initial combination therapy with alogliptin and pioglitazone in drug-naı¨ve patients with type 2 diabetes. Diabetes Care 2010, 33:2406-2408. Study 2
• [24]Kaku K, Itayasu T, Hiroi S, Hirayama M, Seino Y: Efficacy and safety of alogliptin added to pioglitazone in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial with an open-label long-term extension study. Diabetes Obes Metab 2011, 13:1028-1035.
• [25]Seino Y, Fujita T, Hiroi S, Hirayama M, Kaku K: Efficacy and safety of alogliptin in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, dose-ranging comparison with placebo, followed by a long-term extension study. Curr Med Res Opin 2011, 9:1781-1792. Study 1
• [26]Seino Y, Fujita T, Hiroi S, Hirayama M, Kaku K: Alogliptin plus voglibose in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial with an open-label, long-term extension. Curr Med Res Opin 2011, 27(S3):21-29. Study 2
• [27]Esposito R, Cozzolino D, Bellastella G, Maiorino MI, Chiodini P, Ceriello A, Giugliano D: Dipeptidyl peptidase-4 inhibitors and HbA1c target of < 7% in type 2 diabetes: Meta-analysis of randomized controlled trials. Diabetes Obes Metab 2011, 13:594-603.
• [28]Triplitt CL, Reasner CA, Isley WL: Diabetes mellitus. In Pharmacotherapy, a pathophysiologic approach. 6th edition. Edited by Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. New York: McGraw-Hill; 2005:1333-63.
• [29]Nathan DM, Singer DE, Hurxthal K, Goodson JD: The clinical information value of the glycosylated hemoglobin assay. N Engl J Med 1984, 310:341-346.
• [30]Fanelli D: How many scientists fabricate and falsify research? a systematic review and meta-analysis of survey data. PLoS One 2009, 4(5):e5738.
• [31]Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE: Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care 2007, 30:1979-1987.
• [32]Ioannidis JPA: Why most published research findings are false. PLoS Med 2005, 2(8):e124. http://www.plosmedicine.org/article/info:doi/10.1371/ webcite
• [33]de Visser SJ, Uchida N, van Vliet-Daskalopoulou E, Fukazawa I, van Doorn MBA, van den Heuvel MW, Machielsen CSM, Uchida E, Cohen AF: Pharmacokinetic differences between Caucasian and Japanese subjects after single and multiple doses of a potential combined oral contraceptive (Org 30659 and EE). Contraception 2003, 68:195-202.
• [34]Lee E, Ryan S, Birmingham B, Zalikowski J, March R, Ambrose H, Moore R, Lee C, Chen Y, Schneck D: Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment. Clin Pharmacol Ther 2005, 78:330-41.
• [35]Peppa M, Vlassara H: Advanced glycation end products and diabetic complications: a general overview. Hormones 2005, 4(1):28-37.
• [36]American Diabetes Association Treatment Algorithm for Type 2 Diabetes Pharmacist’s Letter/Prescriber’s letter 2006, 22(11):221103. http://faculty.ksu.edu.sa/mahaalrasheed/course/453_454/ADA_Diabetes_Treatment_Algorithm%202006.pdf webcite
• [37]Consumer reports health best buy drugs. The oral diabetes drugs: treating type 2 diabetes. Available from: http://www.consumerreports.org/health/pdf/ webcite
• [38]Daousi C, Casson IF, Gill GV, MacFarlane IA, Wilding JPH, Pinkney JH: Prevalence of obesity in type 2 diabetes in secondary care: association with cardiovascular risk factors. Postgrad Med J 2006, 82:280-284.
• [39]Mitri J, Hamdy O: Diabetes medications and body weight. Expert Opin Drug Saf 2009, 8(5):573-584.
• [40]Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR: Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Diabetes Care 2012, 35:1364-1379.
• [41]Monami M, Iacomelli I, Marchionni N, Mannucci E: Dipeptydil peptidase-4 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials. Nutr Metab Cardiovas 2010, 20:224-235.
• [42]Rendell M, Drincic A, Andukuri R: Alogliptin benzoate for the treatment of type 2 diabetes. Expert Opin Pharmacother 2012, 13(4):553-563.
• [43]Andukuri R, Drincic A, Rendell M: Alogliptin: a new addition to the class of DPP-4 inhibitors. Diabetes Metab Syndr Obes 2009, 2:117-126.
• [44]Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC: Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1–based therapies. Gastroenterology 2011, 141(1):150-156.
• [45]Olansky L: Do incretin-based therapies cause acute pancreatitis? J Diabetes Sci Technol 2010, 4(1):228-229.
• [46]Chopra SS: Industry funding of clinical trials: benefit or bias? JAMA 2003, 290(1):113-114.
• [47]Doucet M, Sismondo S: Evaluating solutions to sponsorship bias. J Med Ethics 2008, 34:627-630.
• [48]Walker E, Hernandez AV, Kattan MW: Meta-analysis: its strengths and limitations. Clev Clin J med 2008, 75(6):431-439.