Cardiovascular Risk Profile Of Oral Anti Diabetic Drugs

Oral anti diabetic drugs currently approved for treatment of type 2 diabetes mellitus(DM) consist of
five main groups; biguanides, sulfonylureas, meglitinides, glitazones, alpha glucosidase inhibitors.
Newer compounds like incretinmimetic drugs - glucagon like peptide 1 (GLP 1) analogues,
dipeptidyl peptidase 4 inhibitors, dual peroxisome proliferator activated receptor (PPAR) agonists
(glitazars), amylin mimetic analogues and Sodium glucose transporter 2 inhibitors are also being used
nowadays as anti diabetic drugs.
We have attempted to consider the cardiovascular effects of commonly used oral anti diabetic drugs.
Though tight glycemic control is known to decrease cardiovascular morbidity and mortality, the
review of literature states the increased cardiovascular risks mainly with sulfonylureas, biguanides
and glitazones either alone or in combination. Sulfonylureas exert their action by closing ATP
dependent K+ channels on pancreatic beta cells, which are also known to affect cardiac ATP
dependent K+ channels and thus prevent the protective hyperpolarization of the myocardial cells
during myocardial ischemia.
Biguanides like metformin hamper gastrointestinal absorption of vitamin B group and folic acid and
increase blood homocysteine levels which accelerate atherosclerosis. Hence it is not surprising that
long term use of sulfonylurea and metformin combination may prove detrimental. Effects of
meglitinides are similar to sulfonylureas. Glitazones due to their action of sodium and water retention
and weight gain are unsafe in NYHA class III and IV. Long term adverse effects of alpha glucosidase
inhibitors on morbidity and mortality are not unequivocally recorded.
The newer class of drugs need to have close follow up for early detection of their adverse effects on
cardiovascular system. SGLT 2 inhibitors are likely to produce hypotension or postural hypotension
in diabetics with autonomic involvement or with concurrent use of diuretics. To summarize, the first
four groups of anti diabetic drugs though are very potent, indispensable and effective they still
warrant a word of caution regarding their use, due to their possible cardiac adverse effects.