Sulfonylureas and cardiovascular effects: from experimental data to clinical use. Available data in humans and clinical applications.
OBJECTIVE
33 years after the UGDP study, the question of deleterious effects of the sulfoylurea (SU) is still raised. We have made a systematic review of the literature from experimental studies to clinical and epidemiological studies.


RESULTS
The main molecule studied is glibenclamide (GB). In vitro and in animal studies, GB is both deleterious for ischemic preconditionning (IPC) and protective for arrhythmia during acute ischemia. Glimepiride (GM) and gliclazide (GCZ) do not seem to have effect on IPC. These effects have been few studied in diabetic animals. In human, according to the investigations used, the GB seems nil or suppressing for IPC, it seems elsewhere decreases ventricular arrhythmias during periods of acute ischemia. It is possible that these two actions account for the non-appearance of concordant deleterious effects between short and long-term studies. With regards to other drugs, only the GM has been specifically studied in human and appears to be nil on IPC. The only prospective clinical study available, although not having for objective to answer to this question, is the UKPDS study. This trial demonstrates the absence of deleterious cardiac effects of GB compared to chlorpropamide and particularly compared to insulin.


CONCLUSIONS
In conclusion, in experimental studies the cardiac effects of SU differ: both deleterious and protective for GB, nil for GM and GCZ on IPC. In all cases the clinical consequences seems to be nil.
Riveline
J P
JP
Department of Diabetology, Sud-Francilien Hospital, Corbeil, France. jean-pierre.riveline@libertysurf.fr
Danchin
N
N
Ledru
F
F
Varroud-Vial
M
M
Charpentier
G
G
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D002320:Cardiovascular Physiological Phenomena; D003326:Coronary Circulation / Q000187:drug effects; D005905:Glyburide / Q000009:adverse effects / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D023421:Models, Animal; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000503:physiopathology; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D005905:Glyburide