Oral Antidiabetics

750 Pages·1996·17.041 MB·English

by  J. Kuhlmann (auth.), Professor Dr.med. Jochen Kuhlmann, Professor Dr.med. Walter Puls (eds.)

Handbook of
Experimental Pharmacology
Volume 119
Editorial Board
G.V.R.Born,London
P. Cuatrecasas, Ann Arbor, MI
D. Ganten, Berlin
H. Herken, Berlin
K.L. Melmon, Stanford, CA
Springer-Verlag Berlin Heidelberg GmbH
Oral Antidiabetics
Contributors
H.J. Ahr, S.L. Ali, J.M. Amatruda, E.M. Bardolph, H. Bischoff,
H.H. Blume, E.-M. Bomhard, E. Brendel, L. Groop, F. Hartig,
A. Hasselblatt, L.S. Hermann, B. Junge, J. Köbberling,
H.P. Krause, J. Kuhlmann, K.H. Langer, H.E. Lebovitz,
P.J. Lefebvre, M. Matzke, M.L. McCaleb, G. Neugebauer, M. Noel,
P. Ochlich, U. Panten, H.J. Ploschke, H. Plümpe, E. Prugnard,
W. Puls, W. Rebel, A.J. Scheen, H. Schlecker, F.H. Schmidt,
B.S. Schug, E. Schütz, C. Schwanstecher, M. Schwanstecher,
S. Seip, J. Stoltefuss, R.H. Taylor, N.F. Wiernsperger,
W. Wingender, C. Wünsche
Editors
Jochen Kuhlmann and Walter Puls
Springer
Professor Dr.med. JOCHEN KUHLMANN
Bayer AG
Institut für Klinische Pharmakologie
Aprather Weg
42096 Wuppertal
Germany
Professor Dr.med. WALTER PULS
Krummacher Straße 200
42115 Wuppertal
Germany
With 140 Figures and 85 Tables
ISBN 978-3-540-62456-1 ISBN 978-3-662-09127-2 (eBook)
DOI 10.1007/978-3-662-09127-2
Library of Congress Cataloging·in-Publieation Data. Oral antidiabetics/contrihutors. H.J. Ahr ... /et aLl:
editors, Jochen Kuhlmann and W. Puls. p. em. - (Handbook 01' experimental pharmacology: v. 119)
ISBN 3·540·58990·2 (hardcover: alk. paper) 1. Hypoglycemic agents. 2. Non·insulin·dependent diabetes -
Chemotherapy. I. Ahr. H.J. 11. Kuhlmann, J. (Jochen) III. Puls, Walter. IV. Series. [DNLM: 1.
Hypoglycemic Agents - pharmacology. 2. Hypoglycemic Agents - therapeutie usc. 3. Diahctes Mellitus.
Non·Insulin-Dependent - drug therapy. Wl HA51L v. 119 199h/WK 825 063 1996/ QP905.1I3 vol. 119
[RC661.Al] 615'.ls - dc20 [616.4'62061] DNLMIDLC for Library 01' Congress 96-23697
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Preface
The prevalence of diabetes continues to increase worldwide. Traditionally,
diabetes in its adult form has not been considered a serious life-threatening
disease. This attitude needs to be changed because the complications asso
ciated with the adult form of diabetes affect almost every organ system. The
high morbidity and mortality of non-insulin-dependent diabetes mellitus
(NIDDM) suggest that current treatment strategies are unsatisfactory. We
therefore face an urgent need for new therapeutic approaches.
When the first Handbook 0/ Oral Antidiabetics was edited by H. Maske
in 1971, the risks and benefits associated with the use of oral antidiabetics
were still under discussion. Nowadays, oral antidiabetics hold a strong posi
tion in the long-term treatment of diabetes. Roughly 30% -50% of the
patients with diabetes in Europe and the United States are treated with oral
antidiabetics, chiefly sulfonylureas. While acknowledging the value of the ß
cytotropic sulfonylureas, we also need to recognize important limitations of
their use, e.g., in the treatment of obese diabetic patients.
A re-assessment of the association of biguanides, especially of metformin
treatment, with lactic acidosis by investigators in Sweden has brought a
revival in the use of biguanides. Today, metformin is the only biguanide
recommended for the treatment of NIDDM, and it is included in the large
United Kingdom Prospective Diabetes Study (UKPDS) concerning long
term benefits. Metformin has recently undergone extensive investigations in
the United States and received marketing approval from the Food and Drug
Administration (FDA) at the end of 1994. There is also an increasing
interest in the effect of metformin on insulin resistance, hyperinsulinemia
and other components of the recently recognized "metabolie syndrome" or
"syndrome X."
A brand-new approach to managing IDDM and NIDDM was offered in
the early 1990s by the introduction of a pseudo tetrasaccharide of microbial
origin, which reduces diet-induced hyperglycemia and endogenous insulin
secretion by inhibiting intestinal a-glucosidases. It may be of particular
interest that repeated administration of a glucosidase inhibitor ameliorated
or prevented diabetes-related neuropathy and microvascular complications
in preclinical studies.
We are most grateful to the authors for the high quality of their contri
butions and (in most cases) for their prompt submission of manuscripts. We
VI Preface
believe that the weaIth of knowledge of oral antidiabetics presented he re
offers the clinician the widest possible selection for the optimal treatment of
this widespread disease. We hope this information will stimulate scientists to
improve therapeutic standards by developing agents that may prevent
dangerous late complications or the manifestation of NIDDM.
We would like to thank Mrs. Doris Walker from Springer-Verlag for her
efficient management and editorial ass ist an ce through the entire project. We
would also like to thank Mrs. G. Lion for secretarial and administrative help
of exceptional quality.
JOCHEN KUHLMANN
WALTER PULS
List of Contributors
AHR, H.J., Bayer AG, PH-PD Toxicology, Geb. 514, 42096 Wuppertal,
Germany
ALl, S.L., Zentrallaboratorium Deutscher Apotheker, Ginnheimerstr. 20
65760 Eschborn, Germany
AMATRuDA, J .M., Miles Inc., Pharmaceutical Division, Institute for
Metabolic Disorders, 400 Morgan Lane, West Haven, CT 06516-4175,
USA
BARDoLPH, E.M., Department of Medicine, Royal Naval Hospital, Haslar,
Gosport, Hampshire P012 2AA, United Kingdom
BISCHOFF, H., Bayer AG, Institut für Herz/Kreislauf- und Arteriosklero
seforschung, Geb. 500, 42096 Wuppertal, Germany
BLUME, H.H., Zentrallaboratorium Deutscher Apotheker, Ginnheimerstr.
20, 65760 Eschborn, Germany
BOMHARD, E.M., Bayer AG, Fachbereich Toxikologie, Aprather Weg,
42096 Wuppertal, Germany
BRENDEL, E., Bayer AG, Institut für Klinische Pharmakologie, Geb. 405,
42096 Wuppertal, Germany
GROOP, L., Malmö General Hospital, Department of Endocrinology, Södra
Förstadsg 101,21401 Malmö, Sweden
HARTIG, F., Boehringer Mannheim GmbH, Sandhofer Str. 116, 68305
Mannheim, Germany
HASSELBLATr, A., Institut für Pharmakologie und Toxikologie der Univer
sität, Robert-Koch-Str. 40, 37075 Göttingen, Germany
HERMANN, L.S., Meda Sverige AB, P.O. Box 138, 40122 Göteborg, Sweden
JUNGE, B., Bayer AG, Central Research, Geb. Q 18, 51368 Leverkusen,
Germany
KÖBBERLlNG, J., Ferdinand-Sauerbruch-Klinikum Wuppertal, Akademisches
Lehrkrankenhaus der Heinrich-Heine-Universität Düsseldorf,
Arrenberger Str. 20, 42117 Wuppertal, Germany
VIII List of Contributors
KRAUSE, H.P., Bayer AG, PH-PD Predinical Development, Geb. 402,
42096 Wuppertal, Germany
KUHLMANN, l., Bayer AG, Institut für Klinische Pharmakologie, Geschäfts
bereich Pharma, Aprather Weg, 42096 Wuppertal, Germany
LANGER, K.H., Hoechst AG, Pharma Entwicklung Pathologie H 811,65926
Frankfurt, Germany
LEBOVITZ, H.E., Endocrinology and Metabolism/Diabetes, State University
of New York, 450 Clarkson Avenue, Box 1205, Brooklyn, NY 11203,
USA
LEFEBVRE, P.l., Centre Hospitalier de Liege, Departement de Medecine,
Service de Diabetologie, Nutrition et Maladies metaboliques, CH. U. -
Domaine Universitaire du Sart Tilman, B. 35, 4000 Liege 1, Belgium
MATZKE, M., Bayer AG, Central Research, Geb. Q 18,51368 Leverkusen,
Germany
MCCALEB, M.L., Miles Inc., Pharmaceutical Division, Institute for Metabolie
Disorders, 400 Morgan Lane, West Haven, CT 06516-4175, USA
NEUGEBAUER, G., Boehringer Mannheim Gmbh, Abt. Klinische Phar
makologie, Sandhofer Str. 116, 68305 Mannheim, Germany
NOEL, M., Groupe LIPHA, Centre de Recherche Chilly-Mazarin, 4, rue de
la Division Ledere, 91380 Chilly Mazarin, France
OCHLICH, P., Boehringer Mannheim GmbH, Sandhofer Str. 116, 68305
Mannheim, Germany
PANTEN, U., Institut für Pharmakologie und Toxikologie der Technischen
Universität, Mendelssohnstr. 1, 38106 Braunschweig, Germany
PLOSCHKE, H.l., Bayer AG, PH-R Structural Research, 42096 Wuppertal,
Germany
PLÜMPE, H., Kirschbaum Str. 9,42115 Wuppertal, Germany
PRUGNARD, E., Groupe LIPHA, Centre de Recherche Chilly-Mazarin, 4,
rue de la Division Ledere, 91384 Chilly-Mazarin, France
PULS, W., Krummacher Str. 200, 42115 Wuppertal, Germany
REBEL, W., Boehringer Mannheim GmbH, Sandhofer Str. 116, 68305
Mannheim, Germany
SCHEEN, A.l., Centre Hospitalier de Liege, Departement de Medecine,
Service de Diabetologie, Nutrition et Maladies metaboliques, CH.U. -
Domaine Universitaire du Sart Tilman, B. 35, 4000 Liege 1, Belgium
SCHLECKER, H., Bayer AG, PH-R Structural Research, 42096 Wuppertal,
Germany
List of Contributors IX
SCHMIDT, F.H., Stockacher Str. 1,68239 Mannheim, Germany
SCHUG, B.S., Zentrallaboratorium Deutscher Apotheker, Ginnheimerstr.
20, 65760 Eschborn, Germany
SCHÜTZ, E., Am Bräunling 12,65719 Hofheim-Diedenbergen, Germany
SCHWANSTECHER, c., Institut für Pharmakologie und Toxikologie der
Technischen Universität, Mendelssohnstr. 1, 38106 Braunschweig,
Germany
SCHWANSTECHER, M., Institut für Pharmakologie und Toxikologie der
Technischen Universität, Mendelssohnstr. 1, 38106 Braunschweig,
Germany
SEIP, S., Bayer AG, PH-R Structural Research, 42096 Wuppertal, Germany
STOLTEFUSS, J., Bayer AG, PH-R-CR Medical Chemistry III, Geb. 460,
42096 Wuppertal, Germany
TAYLOR, R.H., Department of Medicine, Royal Naval Hospital, Haslar,
Gosport, Hampshire P012 2AA, United Kingdom
WIERNSPERGER, N.F., Groupe LIPHA, Strategie Development Division,
International Pharmacological Development Department, 34, rue Saint
Romain, 69379 Lyon, Cedex 08, France
WINGENDER, W., Bayer AG, Institut für Klinische Pharmakologie, Geb.
429, 42096 Wuppertal, Germany
WÜNSCHE, C., Bayer AG, PH-R Structural Research, 42096 Wuppertal,
Germany