Exp Clin Endocrinol Diabetes 2006; 114(9): 527-532
DOI: 10.1055/s-2006-949655
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG · Stuttgart · New York

Starting Insulin Therapy in Type 2 Diabetes: Twice-Daily Biphasic Insulin Aspart 30 Plus Metformin versus Once-Daily Insulin Glargine Plus Glimepiride

P. H. Kann 1 , T. Wascher 2 , V. Zackova 3 , J. Moeller 4 , J. Medding 4 , A. Szocs 5 , M. Mokan 6 , F. Mrevlje 7 , M. Regulski 8
  • 1Philipps-Universität Marburg, Zentrum für Innere Medizin, Bereich Endokrinologie & Diabetologie, Marburg, Germany
  • 2Diabetes und Stoffwechselambulanz, Medizinische Universitätsklinik, Graz, Austria
  • 3II. interní klinika - diabetologicke centrum, Pekarska, Brno, Czech Republic
  • 4Clinical Research Department, Novo Nordisk Pharma GmbH, Mainz, Germany
  • 5Károlyi Sándor Kórház, Budapest, Hungary
  • 6I. interná klinika, JKF UK, Martin, Slovakia
  • 7University Medical Center Ljubljana, Department of Endocrinology, Diabetes and Metabolic Diseases, Ljubljana, Slovenia
  • 8Municipal Hospital in Otwock, Department of Internal Diseases, Stefana Batorego Str, Otwock, Poland
Further Information

Publication History

Publication Date:
17 November 2006 (online)

Abstract

Aim: To compare the efficacy and safety of two analog insulins as starting regimens in insulin-naïve Type 2 diabetes patients. Methods: In this randomized, open-label parallel study, twice-daily biphasic insulin aspart 30 (30% soluble and 70% protaminated insulin aspart; BIAsp 30) plus metformin (met) was compared with once-daily insulin glargine (glarg) plus glimepiride (glim) in 255 insulin-naïve patients (131 male; mean±SD age, 61.2±9.1 years). Mean baseline HbA1c (±SD) was 9.2±1.4% and 8.9±1.3% for BIAsp 30 plus met (n=128) and glarg plus glim (n=127), respectively (P=0.0747). Primary endpoint was the difference in absolute change in HbA1c between groups after 26 weeks of treatment. Results: HbA1c change was significantly greater in the BIAsp 30 plus met group than the glarg plus glim group (between-group difference: -0.5% (95% CI: -0.8; -0.2); P=0.0002). Mean prandial plasma glucose increment was significantly lower for BIAsp 30 plus met compared with glarg plus glim: 1.4±1.4 mmol/l vs. 2.2±1.8 mmol/l; P=0.0002. During the maintenance phase (weeks 6-26), one major hypoglycemic episode occurred in each group; 20.3% and 9% of patients experienced minor hypoglycemic episodes in the BIAsp 30 plus met and glarg plus glim groups, respectively (P=0.0124). At end-of-trial, mean daily insulin doses were 0.40 U/kg BIAsp 30 and 0.39 U/kg glarg. Glarg plus glim-treated patients experienced significant weight gain of 1.5 kg (95% CI: 0.84; 2.19; P<0.0001). Weight change with BIAsp 30 plus met of +0.7 kg was not statistically significant (95% CI: -0.07; 1.42; P=0.0762). Conclusions: Starting insulin in Type 2 diabetes patients with twice-daily BIAsp 30 plus met can reduce HbA1c and mean prandial plasma glucose increment to a greater extent than once-daily glarg plus glim.

References

  • 1 Alvarsson M, Sundkvist G, Lager I, Henriccson M, Berntorp K, Fernqvist-Forbes E, Steen L, Westermark G, Westermark P, Orn T, Grill V. Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients.  Diabetes Care. 2003;  26 2231-2237
  • 2 European Diabetes Policy Group . A desktop guide to type 2 diabetes mellitus.  Diabet Med. 1999;  16 716-730
  • 3 Fritsche A, Schweitzer MA, Haring HU. 4001 Study Group . Glimepiride combined with morning insulin glargine, bedtime neutral protamine hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes. A randomized, controlled trial.  Ann Intern Med. 2003;  138 952-959
  • 4 Howey DC, Bowsher RR, Brunelle RL, Wordsworth JR. [Lys(B28), Pro(B29)]-human insulin: a rapidly absorbed analogue of human insulin.  Diabetes. 1994;  43 396-402
  • 5 Makimattila S, Nikkila K, Yki-Jarvinen H. Causes of weight gain during insulin therapy with and without metformin in patients with Type II diabetes mellitus.  Diabetologia. 1999;  42 406-412
  • 6 Malone JK, Bai S, Campaigne BN, Reviriego J, Augendre-Ferrante B. Twice-daily pre-mixed insulin rather than basal insulin therapy alone results in better overall glycemic control in patients with type 2 diabetes.  Diabet Med. 2005;  22 374-381
  • 7 Malone JK, Kerr LF, Campaigne BN, Sachson RA, Holcombe JH. Lispro Mixture-Glargine Study Group . Combined therapy with insulin lispro Mix 75/25 plus metformin or insulin glargine plus metformin: a 16-week, randomized, open-label, crossover study in patients with type 2 diabetes beginning insulin therapy.  Clin Ther. 2004;  26 2034-2044
  • 8 Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients.  Diabetes Care. 2003;  26 881-885
  • 9 Mudaliar S, Lindberg FA, Joyce M, Beerdsen P, Strange P, Lin A, Henry RR. Insulin aspart (B28 Asp-insulin): a fast-acting analog of human insulin: absorption kinetics and action profile compared with regular human insulin in healthy nondiabetic subjects.  Diabetes Care. 1999;  22 1501-1506
  • 10 Polonsky KS, Given BD, Hirsch LJ, Tillil H, Shapiro ET, Beebe C, Frank BH, Galloway JA, Van Cauter E. Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus.  N Engl J Med. 1988;  318 1231-1239
  • 11 Raskin P, Allen E, Hollander P, Lewin A, Gabbay RA, Hu P, Bode B, Garber A. INITIATE Study Group . Initiating insulin therapy in type 2 diabetes: a comparison of biphasic and basal insulin analogs.  Diabetes Care. 2005;  28 260-265
  • 12 Riddle MC, Rosenstock J, Gerich J. Insulin Glargine 4002 Study Investigators . The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients.  Diabetes Care. 2003;  26 3080-3086
  • 13 Rosenstock J. Basal insulin supplementation in type 2 diabetes: refining the tactics.  Am J Med. 2004;  116 ((Suppl. 3A)) 10S-16S
  • 14 Turner RC, Cull CA, Frighi V, Holman RR. for the UK Prospective Diabetes Study (UKPDS) Group . Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus. Progressive requirement for multiple therapies (UKPDS 49).  JAMA. 1999;  281 2005-2015
  • 15 UK Prospective Diabetes Study Group . Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).  Lancet. 1998;  352 837-883
  • 16 UKPDS Group . UK Prospective Diabetes Study 16: overview of six years' therapy of type 2 diabetes-a progressive disease.  Diabetes. 1995;  44 1249-1258
  • 17 World Medical Association . Revising the declaration of Helsinki.  Bull Med Ethics. 2000;  158 9-11
  • 18 Wright A, Burden AC, Paisey RB, Cull CA, Holman RR. U.K. Prospective Diabetes Study Group . Sulfonylurea inadequacy: efficacy of addition of insulin over 6 years in patients with type 2 diabetes in the U.K. Prospective Diabetes Study (UKPDS 57).  Diabetes Care. 2002;  25 330-336

Correspondence

Peter H.Kann 

Philipps-Universität Marburg·Zentrum für Innere Medizin·Bereich Endokrinologie & Diabetologie

Baldingerstraße

35043 Marburg

Germany

Phone: +49/6421/28 63 13 5

Fax: +49/6421/28 62 73 3

Email: kannp@med.uni-marburg.de

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