Page 323 - fbkCardioDiabetes_2017

Double Trouble - Diabetes and Heart Disease (CAD) 299

Pioglitazone is also a member of the thiazolidinedi- has potential benefits on cardiovascular outcomes
one group which is extensively used in clinical prac- in patients with diabetes. However the potential
tice. In the Prospective Pioglitazone Clinical Trial in for precipitating lactic acidosis in patients receiv-
Macrovascular Events (PRO-active) , treatment with ing Metformin and having concomitant heart or re-
pioglitazone produced a non-significant reduced risk nal dysfunction is well recognised. Metformin must
of coronary and peripheral vascular events (hazard therefore be avoided in patients with acute coronary
ratio [HR], 0.90; 95% CI, 0.80 to 1.02; P=0.10). In ad- syndromes and patients with unstable or acute heart
dition, a meta-analysis of CV outcome from 19 ran- failure which pose risk of hypoperfusion and hypox-
domized clinical trials, with a total of 16,390 diabetic emia. Stable compensated heart failure is however,
patients, showed that pioglitazone was associated not considered a contraindication to the use of met-
with a significantly lower risk of the composite of formin. It may also be prudent to avoid the use of
death, myocardial infarction, and stroke (HR, 0.82; metformin prior to and immediately after the admin-
95% CI, 0.72 to 0.94; P=0.005). (10) However there is istration of contrast agents in the setting of coronary
a concern on serious risk of worsening heart failure angiography, though the evidence for this recom-
that was demonstrated in both the PROactive trial mendation is not strong.
and the meta-analysis on use of pioglitazone. How- Insulin: Glycemic control with insulin has shown car-
ever this did not translate into increased mortality in diovascular benefit in type 1 diabetics ( DCCT/EDIC
these studies. Caution is advised in using pioglita- trials).The true effect in type 2 diabetics is unclear.
zone in patients with heart failure.
However Insulin promotes weight gain that may ac-
DPP-4 Inhibitors: The SAVOR-TIMI 53, EXAMINE & centuate the disordered body habitus in type 2 di-
TECOS trials have examined dipeptidyl peptidase 4 abetics and this may be counterproductive to the
(DPP-4) inhibitors and their effect on cardiovascular development of cardiovascular disease. Thus pa-
outcomes. Though none of these trials demonstrated tients must be advised to have sufficient dietary and
adverse or beneficial cardiovascular outcomes, they lifestyle modifications to maintain optimum weight
raised concerns over the use of DPP 4 Inhibitors and when on therapy with insulin.
associated heart failure. The FDA recommends dis- Diabetic agents and weight gain: Obesity and abdom-
continuation specifically of saxagliptin and alogliptin inal adiposity are risk factors for diabetes and also
in patients who develop heart failure (10) (11). Further, pose an adverse cardiovascular risk as well. Agents
large scale studies on the safety of these drugs is used in the management of diabetes may influence
underway.
this and be weight neutral or can promote weight
SGLT 2 Inhibitors: SGLT 2 Inhibitors like Empagifloz- loss or weight gain.
in and Canagliflozin are novel oral hypoglycaemic
agents. Multiple trials examining their association Drug Effect Drug name Weight effects
with cardiovascular disease, have been performed (Kg)
in patients with high risk of coronary artery disease. Insulin + 4-5
In a trial examining the effects of empagiflozin, at Sulfonylureas +1.6-2.6
three years of taking the drug, the primary outcome Weight gain Meglitinides +0.7-1.7
(a composite of death from cardiovascular causes, Thiazolidinediones +4.1-4.8
nonfatal myocardial infarction, or nonfatal stroke)
occurred in fewer patients assigned to empagiflozin DPP inhibitors +0.00 to 0.4
than to placebo (10.5 versus 12.1 percent; hazard ra- Weight neutral Alpha glucosidase + 0.0 to 0.2
tio [HR] pooled analysis 0.86, 95% CI 0.74-0.99). The inhibitor
findings were driven by a significant reduction in risk Metformin -4.58 to +0.4
of death from cardiovascular causes (3.7 versus 5.9 GLP 1 analogues -2.7 to -3
percent with placebo; HR 0.62, 95% CI 0.49-0.77). The Weight loss SGLT 2 Inhibitors 2 to 3
rate of heart failure related hospitalisations were also
lower in this group. However despite this benefit, Amylin analogues -3.1
canagliflozin increased the rates of toe and mid foot Role of aspirin for risk reduction: Despite the estab-
amputations. Further studies regarding the same are lished role of aspirin in diabetic patients for second-
ongoing and data that emerges may consolidate the ary prevention of cardiovascular disease, the role in
position of SGLT inhibitors as potential cardio-protec- primary prevention is less clear. In a meta-analysis of
tive agents. 10 trials evaluating aspirin for the primary prevention
Metformin: Based on the UKPDS study, Metformin of CVD in patients with diabetes, aspirin modestly

Cardio Diabetes Medicine