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

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
• 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
• 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
• 4 Mathieu C. The scientific evidence: vildagliptin and the benefits of islet enhancement.  Diabetes Obes Metab. 2009;  11 9-17
• 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
• 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
• 7 Triplitt CL. New technologies and therapies in the management of diabetes.  Am J Manag Care. 2007;  13 547-554
• 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
• 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
• 10 Saltiel AR, Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type 2 diabetes.  Diabetes. 1996;  45 1661-1669
• 11 Rendell M. The role of sulphonylureas in the management of type 2 diabetes mellitus.  Drugs. 2004;  64 1339-1358
• 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
• 13 Summary of American Heart Association . Diet and Lifestyle Recommendations Revision 2006.  Arterioscler Thromb Vasc Biol. 2006;  26 2186-2191
• 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
• 15 Winer BJ. Statistical Principles in Experimental Design. 2nd ed., McGraw-Hill: New York; 1971
• 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
• 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
• 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
• 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
• 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
• 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
• 22 Ahren B, Foley JE. The islet enhancer vildagliptin: mechanisms of improved glucose metabolism.  Int J Clin Pract. 2008;  159 (Suppl) 8-14
• 23 Spiegelman BM. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor.  Diabetes. 1998;  47 507-514
• 24 Hansen PA, Corbett JA. Incretin hormones and insulin sensitivity.  Trends Endocrinol Metab. 2005;  16 135-136
• 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
• 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
• 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
• 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
• 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
• 30 Zwacka TP, Hornbach V, Torzewski J. C-reactive protein-mediated lipoprotein uptake by macrophages.  Circulation. 2001;  103 1194-1197
• 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

Correspondence