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472 Cardio Vascular Safety of Antidiabetic
Drugs Do We Know Enough?

did not find a difference in the primary outcome of Thiazolidinediones:
cardiovascular death, non fatal myocardial infarction, Early clinical trials requested possible reductions in
and non fatal stroke, there was a significantly higher cardiovascular events . In 2007, however evidence
rate of all - cause mortality in the intervention group emerged linking rosiglitazone to an increased risk of
compared with controls. Other studies examining myocardial infarction and death. This observation was

intensive glycemic control strategies did not find a soon replicated by others and extended to include an
significant effect on cardiovascular risk. However, association with heart failure risk.
extended follow- up of these trials suggest, that
intensive treatment may have a legacy effect which is As these retrospective analyses were hypothesis
associated with a lower risk of major cardiovascular generating, a cardiovascular outcome trial was
events. conducted to compare addition of rosiglitazone
with metformin or sulfonylurea monotherapy with
Metformin combination of metformin and sulfonylurea. This
study demonstrated that the risk of cardiovascular
Two clinical trials have randomly allocated patients to death or hospitalization for myocardial infarction
Metformin or a comparator and evaluated the risk of or stroke was similar between treatment groups.
cardiovascular outcomes. In both studies, patients However hospitalization or death attributable to heart
allocated to Metformin use experienced significantly failure was significantly higher in patients allocated
lower rates of cardiovascular events. Metformin has to rosiglitazone use.3
also been shown significantly reduce lipid levels.
Although Pioglitazone doesn’t appear to have the
More recenlty, interest in Metformin has same level of cardiovascular risk as rosiglitazone,
shifted to on examination of its safety in patients there appear to be a higher risk of fractures and
with heart failure. Renal dysfunction and heart cancer.
failure have been longstanding contraindications
for metformin use because of the perceived risk
of lactic acidosis moreover observational studies Alpha-Glucosidase Inhibitors
have demonstrated that metformin use in patients Initial reviews of the placebo controlled studies
with heart failure in associated with a lower risk of suggested that acarbose use was associated with
cardiovascular morbidity and mortality. None of the a significantly lower risk of myocardial infarction
patients allocated to metformin use in the UKPDS and other cardiovascular events. This reduction
study developed Lactic acidosis. These observations in cardiovascular risk was thought to be linked
may be influencing requests to regulatory agencies to reduction in blood pressure, post prandial
to revisit previous restrictions on metformin use in hyperglycemia and lipid levels as well as a neutral
patients with heart failure & reduced renal function.1 effect on weight. However, as more comprehensive
reviews of the literature was unable to find a
Sulfonyl Ureas: difference in cardiovascular risk associated with any
Interestingly, sulfonylureas are frequently used even alpha-glucosidase inhibitors, including acarbose.
though question of cardiovascular safety were raised
over 40 yrs ago concern began when the university Dpp4 - Inhibitors : Evidence From Studies :
group Diabetes program (UGDP) investigators SAVOR-TIMI study showed that the use of saxagliptin
reported a significantly higher rate of cardiovascular did not alter the rate of ischemic events. However the
deaths in patients using tolbutamide compared with rate of hospitalization for heart failure was increased.
placebo. 4

When information from both direct and indirect The TECOS trial showed that adding sitagliptin to
comparisons among sulfonylureas is combined, therapy did not
gliclazide appears to have the lowest risk of increase the risk of MACE hospitalization for heart
cardiovascular morbidity and mortality, followed by failure or other adverse events. 5
glymepride, glipizide, and glyburide.2 Based on these
observation, it is important to consider sulfonylureas Linagliptin is not associated with increased
as individual agents when examining the adverse cardiovascular risk. In April 2016 the FDA warned
cardiovascular effects of these drugs. that the DPP-4 inhibitor saxagliptin, alogliptin may
increase the risk of heart failure, especially in patients
with pre existing heart failure or renal impairment.

GCDC 2017