Type 2 diabetes mellitus (formerly named non-insulin-dependent diabete
s mellitus or NIDDM) is a heterogeneous disease resulting from a dynam
ic interaction between defects in insulin secretion and insulin action
. Various pharmacological approaches can be used to improve glucose ho
meostasis via different modes of action: sulphonylureas essentially st
imulate insulin secretion, biguanides (metformin) act by promoting glu
cose utilisation and reducing hepatic glucose production, alpha-glucos
idase inhibitors (acarbose) slow down carbohydrate absorption from the
gut and thiazolidinediones (troglitazone) enhance cellular insulin ac
tion on glucose and lipid metabolism. These pharmacological treatments
may be used individually for certain types of patients, or may be com
bined in a stepwise fashion to provide more ideal glycaemic control fo
r most patients. Selection of oral antihyperglycaemic agents as first-
line drug or combined therapy should be based on both the pharmacologi
cal properties of the compounds (efficacy and safety profile) and the
clinical characteristics of the patient (stage of disease, bodyweight,
etc.). Mildly hyperglycaemic patients should preferably be treated wi
th metformin, acarbose or thiazolidinediones (which are not associated
with any hypoglycaemic risk), while more severely hyperglycaemic indi
viduals should receive a sulphonylurea. In moderately hyperglycaemic p
atients, sulphonylureas should be preferred in nonobese patients while
metformin, and probably also thiazolidinediones, should have priority
in obese insulin-resistant type 2 diabetic patients. Acarbose is main
ly indicated to reduce post-prandial glucose fluctuations and improve
glycaemic stability. Each antihyperglycaemic agent may also be combine
d with insulin therapy to improve glycaemic control and/or reduce the
insulin requirement of diabetic patients after secondary failure to or
al treatment. Finally, safety should be taken into account in elderly
patients and/or those with renal impairment, especially as far as the
use of sulphonylureas (higher risk of hypoglycaemia) and metformin (hi
gher risk of lactic acidosis) is concerned.