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560 Cardio Diabetes Medicine 2017

Glucose Lowering Strategies and

Cardiovascular Outcomes

Dr. Rakesh Sahay

Prof. & Head Department of Endocrinology
Osmania Medical College and Hospital, Hyderabad
Dr. Ella Reddy Chintala

Senior Resident, Department of Endocrinology

Introduction come studies, including the seminalDiabetes Control
Cardiovascular disease is the leading cause of mor- and ComplicationsTrial (DCCT) and UK Prospective
bidityand death in people with diabetes mellitus. DiabetesStudy (UKPDS), HbA1c was establishedas a
While worseninghyperglycemia is directly associat- surrogate biomarker of glycaemiccontrol and thera-
ed with pooreroutcomes, studies aiming at euglyce- peutic goals were set accordingly (6).
mia have failed toshow an advantage over modest
glucose lowering strategies. Several diabetes drugs Cv Outcome Studies And Antidiabetic Drugs
that were approved solely onthe basis of their glu- CV safety trials of all new antihyperglycemic thera-
cose-lowering potential were latershown to increase pies have been mandated by the USFood and Drug
cardiovascular risk. Administration (FDA) since 2008. However, at least
three CV outcomestudies predated that mandate.
Background The UGDP trial [7] suggested that treatment with
Since the 2008 FDA Guidance for industry “Diabetes theshort-acting sulfonylurea tolbutamide was associ-
Mellitus Evaluating Cardiovascular Risk in New Anti- ated with an increase in CV death.However, concern
diabeticTherapies in Type 2 Diabetes” [1] sponsors of about methodology limited the impact of this study.
allnew antihyperglycemic drugs should demonstrate Although not designed to test the CV safety of met-
that the therapy will not result in an unacceptable formin, a secondary analysis of overweight patientsin
increase in CV risk. Among the evaluated endpoints the UKPDS sub study showed that treatment with
stand cardiovascular mortality, myocardial infarction metformin was associated with a 39%reduction in MI,
and stroke, but also can include hospitalization for compared with diet and exercise [8]. The PRO-AC-
acute coronary syndrome, urgent revascularization TIVE study failed to showbenefit of pioglitazone
procedures, and possibly other endpoints. Moreover, in the primary endpoint (a composite of death, MI,
the FDA favours the enrolment of high-risk patients, stroke, acute coronary syndrome, leg revasculariza-
such as those with relatively advanced disease, el- tion or amputation, percutaneous coronaryinterven-
derly patients, or under some degree of renal im- tion, or coronary artery bypass graft) [9], but did show
pairment. Along the lines of the FDA, the European a significant 16% reductionin the 3-point major ad-
Medicines Agency (EMA) [2] also requires an overall verse CV event (MACE) endpoint (CV death, non fatal
assessment of safety to exclude that a new drug MI and non fatal stroke), which has been a more typ-
increases the risk of macro vascular complications ical endpoint for CV trials [10]. The ORIGIN study was
such as CVD. designed to test the hypothesis that treatment with
glargine insulin might reducesecondary CVD events
The goals of antidiabetic treatment are to avert the in patients with CVD and prediabetes or recent onset
untoward metabolic effects of high glucose concen- diabetes. Theresults showed no difference between
trations and prevent microvascular and macrovascu- glargine and placebo in the occurrence of the 3-point
lar complications. Compelling data in type 2diabetic MACE endpoint [11].
patients support the conclusionthat improved long-
term glycaemic controlreduces the risk of microvas-
cular complications (3-5). Based on several largeout-

GCDC 2017