PharmaNews PARO #10. The use of antidiabetic drugs in heart failure

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THE USE OF ANTIDIABETIC DRUGS IN HEART FAILURE

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PHARMANEWS PARO #10

THE USE OF ANTIDIABETIC DRUGS IN HEART FAILURE Keywords: SGLT2 inhibitors, Antidiabetics, Pharmacology, Mellitus diabetes, mechanism of action.

Introduction Sodium-glucose co-transporter type 2 (SGLT2) inhibitor antidiabetic drugs have been shown in many clinical studies to be very effective in reducing the risk of hospitalizations for heart failure in diabetic patients. In different settings, the relative reduction in hospitalization has been approximately 30-35% compared to the groups that did not receive an SGLT2 inhibitor. Cardiovascular studies showed that the use of SGLT2 inhibitors is associated with a reduction in new atherothrombotic events in patients in secondary prevention, however, there was also a great improvement in the reduction of traditional cardiovascular risk factors, such as weight reduction, blood pressure, glycemia. As well as there were also short-term hemodynamic benefits.

Figure

1:

kidney, majority

Glucose

Normally of

reabsorption

SGLT2

glucose

by

the

reabsorbs

the

filtered

by

the

kidney, but SGLT2 inhibitors reduce the renal reabsorption of glucose, producing an

increase

in

glucose

excretion

decrease in plasma glucose.

and

a

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Mechanism of action SGLT2

inhibitors

reabsorption convoluted

in

reduce

the

tubule,

first

Among the most widely seen therapeutic targets is the sodium

and

segments

leading

to

of

glucose

the

glycosuria,

distal

osmotic

inhibition

exchanger

in

of the

the

sodium

heart,

and

producing

hydrogen a

ion

decrease

in

sodium cardiomyocyte concentrations, indirectly of calcium,

reducing

the

possible

toxic

effects

diuresis, and natriuresis. It was then postulated that

associated with the accumulation of cations. At the

diuresis

in

cardiac level, SGLT2 inhibitors have an inhibitory

intravascular volume, which would imply a decrease

effect on calmodulin-dependent protein kinase type

in myocardial work through a reduction in preload

II (CaMKII), which regulates calcium homeostasis

and afterload.

and can increase cell viability.

and

natriuresis

Renoprotection

decrease

have

kinase (AMPK) activity associated with the use of

mainly been in the reduction of proteinuria and in

SGLT2 inhibitors have decreased the activity of the

better preservation of the glomerular filtration rate.

multiprotein

Thus,

decreases

it

SGLT2

has

been

pathophysiological syndrome,

that

mechanism

a

a

In cardiac fibroblasts, the increase in AMP-activated

with

been

cause

in

studies

has

could

consistent

inhibitors.

postulated, complex

the

benefits

supported

called

renoprotection

for

The

finding

a

by

the

cardio-renal

may

be

improvement

of

an

the

inflammasome

complex,

inflammatory

response

which and

the

production of fibrous tissue.

indirect

ventricular

function.

Dosage and adverse effects

Also at the renal level, the increased supply of sodium to the distal segments of the nephron is a stimulus to

Dapagliflozin, 10 mg once daily, for the treatment of

cause vasoconstriction of the afferent arteriole, with

heart failure patients with reduced ejection fraction.

the consequent decrease in renal blood flow, which

The

could explain an increase in erythropoietin release. As

bacterial infections of the genito-urinary tract.

a consequence, a stimulus for erythropoiesis would occur with an increase in oxygen transport to the tissues.

Additionally,

erythropoietin

has

most

frequent

adverse

effect

is

fungal

and

Conclusion

been

associated with decreased inflammation and reduced

The discovery of its beneficial effects in heart failure

left ventricular mass.

has

allowed

an

important

change

in

its

pharmacological profile and in its clinical utility.

It has been shown that alterations in cardiac ATP

This characteristic is unique since no other type of

production occur in the pathophysiology of diabetes

hypoglycemic drugs has been shown to be effective

mellitus,

ketone

in reducing the serious events associated with heart

oxidation; In these cases, ATP is covered mainly by

failure. The clinical benefits demonstrated by these

fatty acid oxidation, all these alterations are increased

antidiabetics for the treatment of heart failure with

in

reduced ejection fraction are also achieved in both

heart

which

failure,

decrease

but

can

glycolysis

be

from

reversed

by

SGLT2

inhibitors and it has been seen that ATP production mechanisms

can

have

a

positive

impact

on

diabetics and non-diabetics.

the

ventricular contractile function.

All credits of scientific information are for the authors of the scientific article creation!

Scientific information reference: Quesada, D. J. (2020). El uso de los inhibidores de SGLT2 en falla cardiaca. Revista MĂŠdica PeriĂłdica, 1-4.

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