Response to anti-diabetic medications is not always predictable or favourable even in phenotypically similar type-2 diabetes
(T2D) cases. This is not only due to patient’s compliance and access to care but is also considered to be an effect of idiosyncratic differences
among individuals, stemming from the combination of their unique genetic background and environmental exposures. In this systematic
review, we aimed to summarise the available evidence on pharmacogenetic and pharmacogenomic studies of oral agents for T2D
that are currently in the market and describe the agents studied, the targeted loci in regards to the efficacy and the toxicity profile of the
agents included. We included 53 studies published between 2003-2012, which examined the following anti-diabetic classes: sulphonylureas,
metformin, metiglinides and thiazolidenediones. There were no published studies on newer agents (e.g. incretin based treatments).
Forty-nine studies (92.5%) examined the therapeutic response to oral antiglycaemic agents. Outcomes assessed included changes in
metabolic markers (fasting or postprandial blood glucose, fasting or postprandial insulin, HbA1c), Homeostasis Assessment Model
(HOMA)-Insulin Resistance (IR) or HOMA-B-cell function (HOMA-B), and time to monotherapy failure. Regarding side effects, hypoglycaemia
and TZD-related oedema were the most commonly assessed. In the vast majority of the studies included (n=38, 71.7%), more
than one outcomes (n=27, 50.9%) and/or more than one SNPs (n=21, 39.6%) were evaluated in the same publication, but most studies
examined one drug (n=50, 94.3%). A considerable number of the proposed genes seem to be related to beta-cell development and function,
but there are several genes whose underlying pathway linked to diabetes pharmacotherapy remains poorly understood. Pharmacogenomics
are still not in pace with the wealth of information provided by GWAS in the genetics of T2D and related traits and the proposed
associations need further validation in well-characterized large studies of varying ancestral origins.