Download PDF
Horm Metab Res 2010; 42(9): 663-669
DOI: 10.1055/s-0030-1255036
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Effects of One Year Treatment of Vildagliptin Added to Pioglitazone or Glimepiride in Poorly Controlled Type 2 Diabetic Patients

G. Derosa1 , P. Maffioli1 , I. Ferrari1 , R. Mereu1 , P. D. Ragonesi2 , F. Querci3 , I. G. Franzetti4 , G. Gadaleta5 , L. Ciccarelli6 , M. N. Piccinni7 , A. D’Angelo1 , S. A. T. Salvadeo1
  • 1Department of Internal Medicine and Therapeutics, University of Pavia,Pavia, Italy
  • 2Diabetes Care Unit, S. Carlo Hospital, Milano, Italy
  • 3Ospedale Pesenti Fenaroli, Alzano Lombardo, Bergamo, Italy
  • 4Metabolic Unit, Regional Hospital, Varese, Italy
  • 5Division of Medicine, Civic Hospital, Cittiglio, Varese, Italy
  • 6RSA Don Leone Porta, Milano, Italy
  • 7Fondazione Ospedale della Carità, Casalbuttano, Cremona, Italy
Further Information

Publication History

received 08.01.2010

accepted 03.05.2010

Publication Date:
17 June 2010 (online)

Also available at
    Permissions and Reprints

Abstract

The aim of the study was to compare the effects of vildagliptin added to pioglitazone or glimepiride on metabolic and insulin resistance related-indices in poorly controlled type 2 diabetic patients (T2DM). 168 patients with T2DM were randomized to take either pioglitazone 30 mg once a day plus vildagliptin 50 mg twice a day or glimepiride 2 mg 3 times a day plus vildagliptin 50 mg twice a day. We evaluated body weight, body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment β-cell function index (HOMA-β), fasting plasma proinsulin (FPPr), proinsulin/fasting plasma insulin ratio (Pr/FPI ratio), adiponectin (ADN), resistin (R), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (Hs-CRP) at their baseline values, and after 3, 6, 9, and 12 months of treatment. We observed a similar improvement of HbA1c, FPG, PPG, and Hs-CRP compared to baseline in the 2 groups. Fasting plasma insulin, FPPr, Pr/FPI ratio, R, and TNF-α were significantly decreased and ADN was significantly increased with pioglitazone plus vildagliptin, but not with glimepiride plus vildagliptin. HOMA-IR, and HOMA-β values obtained with pioglitazone plus vildagliptin were significantly better than the values obtained with glimepiride plus vildagliptin. Pioglitazone plus vildagliptin were found to be more effective in preserving β-cell function, and in reducing insulin resistance, and inflammatory state parameters.

Key words

vildagliptin - pioglitazone - glimepiride - insulin resistance - β-cell - inflammatory state

References

  • 1 Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial.  Diabetes Obes Metab. 2007;  9 194-205
    Google Scholar
  • 2 Saydah SH, Fradkin J, Cowie CC. Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes.  JAMA. 2004;  291 335-342
    Google Scholar
  • 3 Canadian Diabetes Association, Clinical Practice Guidelines Expert Committee: Canadian Diabetes Association . Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada.  Can J Diabetes. 2003;  27 S1-S152
    Google Scholar
  • 4 Mathieu C. The scientific evidence: vildagliptin and the benefits of islet enhancement.  Diabetes Obes Metab. 2009;  11 9-17
    Google Scholar
  • 5 Tourrel C, Bailbé D, Meile MJ, Kergoat M, Portha B. Glucagon-like peptide-1 and exendin-4 stimulate beta-cell neogenesis in streptozotocin-treated newborn rats resulting in persistently improved glucose homeostasis at adult age.  Diabetes. 2001;  50 1562-1570
    Google Scholar
  • 6 Perfetti R, Zhou J, Doyle ME, Egan JM. Glucagon-like peptide-1 induces cell proliferation and pancreatic-duodenum homeobox-1 expression and increases endocrine cell mass in the pancreas of old, glucose-intolerant rats.  Endocrinology. 2000;  141 4600-4605
    Google Scholar
  • 7 Triplitt CL. New technologies and therapies in the management of diabetes.  Am J Manag Care. 2007;  13 547-554
    Google Scholar
  • 8 Bosi E, Camisasca RP, Collober C, Rochotte E, Garber AJ. Effects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin.  Diabetes Care. 2007;  30 890-895
    Google Scholar
  • 9 Triplitt C, McGill JB, Porte Jr D, Conner CS. The changing landscape of type 2 diabetes: the role of incretin-based therapies in managed care outcomes.  J Manag Care Pharm. 2007;  13 S2-S16
    Google Scholar
  • 10 Saltiel AR, Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type 2 diabetes.  Diabetes. 1996;  45 1661-1669
    Google Scholar
  • 11 Rendell M. The role of sulphonylureas in the management of type 2 diabetes mellitus.  Drugs. 2004;  64 1339-1358
    Google Scholar
  • 12 European Association for the Study of Diabetes (EASD) . Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD).  Eur Heart J. 2007;  28 88-136
    Google Scholar
  • 13 Summary of American Heart Association . Diet and Lifestyle Recommendations Revision 2006.  Arterioscler Thromb Vasc Biol. 2006;  26 2186-2191
    Google Scholar
  • 14 Derosa G, Maffioli P, Salvadeo SA, Ferrari I, Ragonesi PD, Querci F, Franzetti IG, Gadaleta G, Ciccarelli L, Piccinni MN, D’Angelo A, Cicero AF. Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients.  Metabolism. 2010;  59 887-895
    Google Scholar
  • 15 Winer BJ. Statistical Principles in Experimental Design. 2nd ed., McGraw-Hill: New York; 1971
    Google Scholar
  • 16 Göke B, Hershon K, Kerr D, Calle Pascual A, Schweizer A, Foley J, Shao Q, Dejager S. Efficacy and safety of vildagliptin monotherapy during 2-year treatment of drug-naïve patients with type 2 diabetes: comparison with metformin.  Horm Metab Res. 2008;  40 892-895
    Google Scholar
  • 17 Foley JE, Sreenan S. Efficacy and safety comparison between the DPP-4 inhibitor vildagliptin and the sulfonylurea gliclazide after two years of monotherapy in drug-naïve patients with type 2 diabetes.  Horm Metab Res. 2009;  41 905-909
    Google Scholar
  • 18 Goodman M, Thurston H, Penman J. Efficacy and tolerability of vildagliptin in patients with type 2 diabetes inadequately controlled with metformin monotherapy.  Horm Metab Res. 2009;  41 368-373
    Google Scholar
  • 19 Garber AJ, Foley JE, Banerji MA, Ebeling P, Gudbjörnsdottir S, Camisasca RP, Couturier A, Baron MA. Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea.  Diabetes Obes Metab. 2008;  10 1047-1056
    Google Scholar
  • 20 Rosenstock J, Baron MA, Camisasca RP, Cressier F, Couturier A, Dejager S. Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes.  Diabetes Obes Metab. 2007;  9 175-185
    Google Scholar
  • 21 Fonseca V, Schweizer A, Albrecht D, Baron MA, Chang I, Dejager S. Addition of vildagliptin to insulin improves glycaemic control in type 2 diabetes.  Diabetologia. 2007;  50 1148-1155
    Google Scholar
  • 22 Ahren B, Foley JE. The islet enhancer vildagliptin: mechanisms of improved glucose metabolism.  Int J Clin Pract. 2008;  159 (Suppl) 8-14
    Google Scholar
  • 23 Spiegelman BM. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor.  Diabetes. 1998;  47 507-514
    Google Scholar
  • 24 Hansen PA, Corbett JA. Incretin hormones and insulin sensitivity.  Trends Endocrinol Metab. 2005;  16 135-136
    Google Scholar
  • 25 Pfützner A, Pfützner AH, Larbig M, Forst T. Role of Intact Proinsulin in Diagnosis and Treatment of Type 2 Diabetes Mellitus.  Diabetes Technol Ther. 2004;  6 405-412
    Google Scholar
  • 26 Bouskila M, Pajvani UB, Scherer PE. Adiponectin: a relevant player in PPARγ -agonist mediated improvements in hepatic insulin sensitivity?.  Int J Obes Relat Metab Disord. 2005;  29 S17-S23
    Google Scholar
  • 27 Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity.  Nat Med. 2001;  7 941-946
    Google Scholar
  • 28 Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes.  Nature (London). 2001;  409 307-312
    Google Scholar
  • 29 Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.  Science. 1993;  259 87-91
    Google Scholar
  • 30 Zwacka TP, Hornbach V, Torzewski J. C-reactive protein-mediated lipoprotein uptake by macrophages.  Circulation. 2001;  103 1194-1197
    Google Scholar
  • 31 Mori Y, Itoh Y, Obata T, Tajima N. Effects of pioglitazone vs glibenclamide on postprandial increases in glucose and triglyceride levels and on oxidative stress in Japanese patients with type 2 diabetes.  Endocrine. 2006;  29 143-148
    Google Scholar

Correspondence

G. DerosaMD, PhD 

Department of Internal Medicine

and Therapeutics

University of Pavia, Fondazione

IRCCS Policlinico S. Matteo

P. le C. Golgi 2

27100 Pavia

Italy

Phone: +39/0382/52 6217

Fax: +39/0382/52 6259

Email: giuseppe.derosa@unipv.it

      >