Adverse Cardiovascular Effects of Sulphonylurea Drugs

Abstract

Sulphonylureas are widely used in the treatment of diabetes mellitus. Since the publication of the University Groups Diabetes Program (UGDP) results the discussion on their possible cardiovascular side effects has been lively and sometimes even passionate. The initial UGDP findings about the adverse effects of tolbutamide on the cardiovascular system have been criticised, particularly for shortcomings in the study design. The results of other epidemiological studies of the sulphonylurea effects on cardiovascular morbidity and mortality published this far have been contradictory. This is understandable because the factors involved are very complex. Most of these studies have used tolbutamide only, and the findings cannot necessarily be directly extrapolated to other sulphonylureas. Only properly performed prospective studies may provide further information on this issue. High concentrations of several sulphonylureas may have inotropic effects on heart muscle in in vitro animal models, but human studies performed in vivo do not support the view of clinically significant inotropy for sulphonylureas. High concentrations of tolbutamide or glibenclamide (glyburide) may affect the myocardial metabolism in isolated organs, but the possible clinical significance of these findings remains unknown. Some epidemiological and experimental studies have associated oral antidiabetic treatment with the occurrence of cardiac arrhythmias or increased digitalis toxicity. Only a few results are available, and there may be differences between the sulphonylureas in this respect. Antiaggregatory properties have been postulated for some sulphonylureas. Gliclazide, in particular, has been studied, but some other compounds of this class have also been effective in short term studies. If confirmed, these effects on haemostasis would be noteworthy. The sulphonylurea effects on serum lipids, especially on HDL-cholesterol, have been discussed widely during the last few years. Decreases in HDL-cholesterol concentrations were suggested to be associated with sulphonylurea therapy. However, these findings were not confirmed in recent cross-sectional and longitudinal studies performed with different sulphonylureas. Chlorpropamide, and to a lesser extent tolbutamide, may cause dilutional hyponatraemia and aggravate existing heart failure. Glibenclamide may increase the clearance of water in the kidney.

Association of high-sensitive C-reactive protein with advanced stage β-cell dysfunction and insulin resistance in patients with type 2 diabetes mellitus

“…In this analysis the highest hsCRP levels were also observed in patients receiving sulfonylurea therapy. These results support the hypothesis that cardiovascular disease risk may be associated with sulfonylurea treatment, as suspected decades ago (25,26) and reported again recently (27). Unfortunately, contradicting reports from studies such as the UK Prospective Diabetes Study (UKPDS) did not involve well enough characterized patient populations to allow direct comparison of the results (28).…”

Antidiabetic activity of Boerhaavia diffusa L.: effect on hepatic key enzymes in experimental diabetes

“…It can be managed by exercise, diet and chemotherapy. However, the pharmaceutical drugs are either too expensive or have undesirable side effects or contraindications (Berger, 1985;Huupponen, 1978). Therefore, the search for more effective and safer hypoglycemic agents has continued to an area of active research (Pari and Uma, 1999;Pari and Venkateswaran, 2002).…”

Effect of chronic administration of <i>Boerhaavia diffusa</i> Linn. leaf extract on experimental diabetes in rats

“…In modern medicine, no satisfactory effective therapy is still available to cure diabetes mellitus 2 . Currently available therapeutic options such as dietary modification, oral hypoglycemics and insulin have limitations of their own in treating noninsulin dependent diabetes mellitus (NIDDM) [3][4] . Therefore, the search for more effective and safer hypoglycemic agents has continued to be an area of active research.…”