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Cardio Diabetes Medicine 2017 439

metformin, repaglinide was less effective in reducing but not diastolic BP (DBP); Monotherapy with GLP-
similar CVD biomarkers of inflammation and endo- 1 RA does not increase the risk of hypoglycemia, It
thelial dysfunction in nonobese patients with type has also been reported that β-cell function was im-
2 diabetes mellitus despite similar glycemic control, proved with GLP-1 RA (HOMA-B, proinsulin-to-insulin
The Nateglinide and Valsartan in Impaired Glucose ratio). The cardioprotective effects of GLP-1 agonists
Tolerance Outcomes Research (NAVIGATOR) trial have been well documented in pre-clinical studies.
did not find nateglinide to improve CV outcomes in Indeed, experimental models of ischemia and reper-
patients with impaired glucose tolerance and CVD fusion have shown improved post-ischemic myocar-
or CV risk factors compared to placebo or valsartan dial contractile dysfunction and reduced infarct size
treatment. While valsartan at least decreased the in- with constant infusions of GLP-1demonstrated car-
cidence of type 2 diabetes mellitus by 14% in these diovascular benefits including reduced arrhythmias,
patients, nateglinide had no effect on delaying the improved left ventricle function, and improved endo-
development of diabetes. thelial function, in patients with or without diabetes
and with coronary artery disease and chronic heart
Alpha –Glucosidase Inhibitors failure. Ongoing randomized large-scale trials will
be important to consolidate the results obtained so
Alpha Glucosiase inhibitors is a group of rugs which
can delay release of glucose from complex carbohy- far. Indeed, several GLP-1 RA are undergoing long-
drate and thus leads to a reduction of post prandial term randomized trials to assess their CV safety –
blood glucose levels.. Three drugs in this class are ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN
Acarbose, Voglibose and Miglitol. STOP-NIDDM tri- 6 (semaglutide), REWIND (dulaglutide), and EXSCEL
al has already revealed its efficacy in delaying the (exenatide extended release). The Evaluation of Lix-
development of type 2 diabetes in patients with IGT, isenatide in Acute Coronary Syndrome (ELIXA) trial
It reduces HbA1c and improves Post prandial insulin randomized 6068 patients with T2DM and an acute
levels and insulin sensitivity. STOP-NIDDM trial was coronary event within the last 180 days to receive
the first study to report a significant reduction in lixisenatide or placebo on top of standard of care.(19)
post prandial blood glucose and development of CV After a median follow-up of 25 months, there was no
events of any type MI and new cases of hyperten- difference in the primary composite endpoint of car-
sion. Meta-analysis of seven long term studies shows diovascular death, non-fatal MI, non-fatal stroke, or
highly significant relative risk reduction of 64% for hospitalization for unstable angina between groups
CAD in Acarbose group more in the IGT group. and no difference in heart failure hospitalizations. In
the Liraglutide Effect And Action In Diabetes: Evalu-
ation Of Cardiovascular Outcome Results (LEADER)
Glucagon-Like Peptide 1 Agonists trial, (20) which randomized 9340 T2DM patients
Incretins are enteroendocrine peptides that augment with high cardiovascular risk, liraglutide reduced the
insulin response in a glucose-dependent manner, primary composite endpoint of cardiovascular death,
regulate postprandial glucagon secretion, slow gas- non-fatal MI or non-fatal stroke compared to place-
tric emptying, and increase satiety by central mech- bo after a median follow-up of 3.8 years Although
anisms. Glucagon-like peptide 1 (GLP-1) and glu- not currently FDA-approved, semaglutide, (21) a
cose-dependent insulinotropic polypeptide (GIP) are once-weekly GLP-1 agonist, was non-inferior to pla-
2 of these incretins whose secretions are known to cebo after 26 months follow-up among 3297 patients
be impaired in type 2 diabetes mellitus; GLP-1–based with T2DM in the Trial to Evaluate Cardiovascular and
therapy is meant to address this deficiency. Current- Other Long-term Outcomes with Semaglutide in Sub-
ly, the GLP-1R agonists (GLP-1 RA) approved for the jects with Type 2 Diabetes (SUSTAIN-6) with regards
treatment of T2DM are Albuglutide, Dulaglutide, Ex- to the primary composite endpoint of cardiovascular
enatide and extended release Exenatide, Liraglutide , death, nonfatal MI and non-fatal stroke
Lixisenatide and Semeglutide they have been shown
to provide effective HgA1c reduction of 1%-1.6% Dipeptidyl Peptidase 4 Inhibitors
GLP-1 RA treatment seems to be associated with a Dipeptidyl peptidase 4 (DPP-4) is a ubiquitous en-
favorable impact on several CV risk factors, name- zyme that degrades many targets such as GLP-1;
ly BP, lipid profile and weight. In fact, several meta the pharmacologic inhibition of DPP-4 prolongs the
analyses have demonstrated that GLP-1 RA treatment bioavailability of endogenous GLP-1. Currently, 4
is associated with significant weight loss and bene- DPP-4 inhibitors––sitagliptin, saxagliptin,Vildagliptin,
ficial effects on lipid profile, decreasing LDL-c and linagliptin, alogliptin and Teneligliptin. In addition
TG. These drugs are able to reduce systolic BP (SBP), to their glucose-lowering effects, DPP-4 inhibitors

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