Zusammenfassung
Aus Furcht vor Laktazidosen schließen die gegenwärtigen Metformin-Kontraindikationen
eine Vielzahl von Typ-2-Diabetikern von einer effektiven antihyperglykämischen und
kardiovaskulär protektiven Therapie aus. Jüngste Daten stellen jedoch die traditionellen
Kontraindikationen für Metformin infrage. Da die Inzidenz von Laktazidosen bei Typ-2-Diabetikern
mit und ohne Metformin-Therapie mit jeweils ca. 9 pro 100 000 Patientenjahren identisch
ist, besteht keine Evidenz, dass eine Metformin-Therapie mit einem erhöhten Risiko
für Laktazidosen assoziiert ist. Ebenso wurde trotz häufiger Missachtung gravierender
Metformin-Kontraindikationen keine korrespondierende Steigerung der Inzidenz von Laktazidosen
registriert. Die Metformin-Therapie bei älteren multimorbiden Diabetikern mit expliziten
Kontraindikationen führte zu signifikant günstigeren klinischen Parametern als bei
der Kontrollgruppe ohne Metformin. Laktazidosen fanden sich nicht, bezüglich der Progression
einer Niereninsuffizienz, patientenorientierter Endpunkte und der Gesamtmortalität
ergaben sich keine Unterschiede.
Gegenüber seinen Vorgängersubstanzen Phenformin und Buformin hat Metformin eine erheblich
geringere Lipophilie und kürzere Plasmahalbwertszeit, es wird in unveränderter Form
renal eliminiert. Bei Metformin-therapierten Typ-2-Diabetikern - selbst bei über 70-jährigen
und Niereninsuffizienten im Stadium der kompensierten Retention - konnten keine relevanten
Erhöhungen der Laktatspiegel nachgewiesen werden. Bei Laktazidosen wiesen Metformin-
und Laktatspiegel keine Korrelationen auf, für die Prognose sind weder die Höhe der
Metformin- noch Laktat-Serumkonzentration als vielmehr die ursächliche hypoxische
Grunderkrankung und Komorbidität entscheidend. Diese Befunde lassen an der pathogenetischen
Bedeutung von Metformin bei Laktazidosen Zweifel aufkommen. Aufgrund der aktuellen
Datenlage sind zumindest höheres Lebensalter sowie die kompensierte Nieren- und Myokardinsuffizienz
als Kontraindikationen für Metformin nicht mehr aufrechtzuerhalten. Das Absetzen von
Metformin bereits zwei Tage vor Anwendung von i. v.-Kontrastmitteln bzw. Operationen
mit Allgemeinanästhesie ist unnötig, die letzte Applikation kann am Vorabend des Eingriffs
erfolgen.
Summary
For fear of lactic acidosis the currently listed contraindications to the use of metformin
exclude a large number of people with type 2 diabetes from efficacious antihyperglycaemic
and cardioprotective treatment. Yet recent data call the traditional contraindications
to metformin into question. As the incidence of lactic acidosis in patients with type
2 diabetes is the same with or without metformin therapy (about 9 per 100000 patient
years) there is no evidence that metformin therapy is associated with an increased
risk of lactic acidosis. Similarly, despite disregard internationally of major metformin
contraindications, there has been no corresponding increase in the incidence of lactic
acidosis. Metformin treatment of elderly diabetics with multiple comorbidities and
explicit contraindications has led to significantly better clinical parameters in
them than in the control group without metformin; and there were no cases of lactic
acidosis. The two groups did not differ with regard to progression of renal failure,
patient-oriented endpoints or overall mortality.
Compared with its predecessors phenformin and buformin, metformin is considerably
less lipophilic and has a shorter plasma half-life; it is eliminated renally in unchanged
form. In type 2 diabetics treated with metformin - even those over 70 years of age
and those in mild renal failure - no relevant increases in lactate levels were found.
In patients with lactic acidosis there was no correlation between the levels of metformin
and lactate. The prognosis of lactic acidosis is determined less by the serum concentrations
of metformin and lactate than by the hypoxia caused by the underlying disease and
comorbidities. These findings raise doubts about the significance of metformin in
the pathogenesis of lactic acidosis.
On the basis of the current data, advanced age per se, mild renal impairment and stable
heart failure can no longer be upheld as contraindications to the use of metformin.
It should be safe to withdraw metformin the evening before radiological examinations
with intravenous contrast media or surgical procedures under general anaesthesia in
diabetics with normal renal function.
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1 Teile dieser Arbeit wurden bereits in Diabetologia 2005 Nov 11;1-6 PMID: 16283245
veröffentlicht.
Dr. med. Andreas Holstein
Medizinische Klinik I
Klinikum Lippe-Detmold
Röntgenstraße 18
32756 Detmold
Phone: +49/5231/721171
Fax: +49/5231/721035
Email: Andreas.Holstein@t-online.de
