A new class of anti-diabetic drugs has been shown to protectthe heart while reducing blood sugar! This is important because cardiovasculardisease is today the leading cause of death in India. The prevalence ofcardiovascular disease has increased dramatically to 5.45 crores in 2016, morethan double the 2.57 crores in 1990. Diabetes is a very common and causalassociation for it. We have 70 million diabetics in our country and theirpopulation is increasing exponentially.
The physical characteristics of Indians predispose us to'metabolic syndrome' which includes high blood pressure, high cholesterollevels and obesity which together increase the risk of heart disease andstroke. But independent of these factors, diabetes also adds to the risk ofheart disease. Most management of diabetes takes this into consideration.However, in the treatment of diabetes, it is also important to realise thatthere is another life threatening condition that occurs earlier in diabetes ascompared to others. This is heart failure which is more common than heartattack or stroke, and results from the effects of diabetes on the heart muscle.Recognising heart failure as an important condition is critical and must betaken into consideration in the management of diabetes.
The challenge that doctors face is that only a few studieshave been carried out in the past and even these focused on the effect ofanti-diabetic medication on heart attack and strokes. Several of theanti-diabetic medications in use are either neutral or theoretically increasethe risk of heart failure, but there was a lacuna in the data as there were nolarge scale clinical trials carried out regarding effect on heart failure toconfirm this hypothesis.
Data available on cardiovascular outcomes shows that somedrugs like metformin, which is the commonly prescribed first lineanti-diabetic, reduces the blood sugar but is neutral when it comes to theheart. Others, like sulfonylureas – glipizide and glimepiride were associatedwith adverse cardiac outcomes; and the thiazolidine derivatives – rosiglitazoneand pioglitazone while effective in lowering blood glucose, results in anincrease in heart failure risk. Insulin induces retention of sodium and fluidwhich may accelerate the incidence of failing heart. It is well known thatsulfonylureas, thiazolidinediones and insulin lead to weight gain and increasein blood pressure, which contributes to their adverse effect on the heart inthe long run. Another class of commonly used drugs, the gliptins, in additionto having inconsistent effects of blood pressure and weight, are at best,neutral when it comes to cutting the heart risks.
Clinicians were thus faced with a Hobson's choice with noconvincing data for anti-diabetic drugs with regard to effect on heart failure.But now, a new clinical trial has thrown positive light on a new class ofanti-diabetic drugs known as SGLT2 (sodium-glucose co-transporter 2)inhibitors. SGLT2 blockers are the only molecules that lead to removal ofexcess sugar from the body and this novel mechanism of action confersadditional benefits of weight loss and blood pressure reduction, not seen withany other class of anti-diabetics. Three agents are available from this group.Empagliflazone (Jardiance and Gibtulio), Canagliflazone ( Invokana, Sulisentand Prominad) and Dapagliflazone (Forxiga and Oxra) All three agents have positivedata in this regard.
However the largest clinical data with majority of thepatients having no underlying clinical atherosclerotic disease is withDapagliflazone. The trial DECLARE-TIMI 58 conducted across 33 countries, showedunprecedented benefit in form of significant reduction in heart failure andcardiac mortality while also reducing other major cardiac events in 17000patients with Type 2 diabetes, a large proportion of who did not have any overtheart disease.
The trial showed that the drug, known as Dapagliflozin,actually reduced heart risk through a positive effect on cardiac function,thereby protecting the heart along with controlling the blood sugar. Though themechanism for such impressive benefits remain unclear, removal of excess glucosealong with sodium and water, preventing fluid overload, that is, too much waterin the body and reducing the work the heart needs to do, may be a possiblemechanism.
The results are heartening for patients with diabetes aswell as the doctors treating them, as Dapagliflozin now gives them an option toreduce risk of heart failure along with controlling blood sugar. The trial alsoshows that the drug improves kidney function. Available evidence with largeclinical studies shows that SGLT2 inhibitors should be preferred as an add-ontherapy for all type 2 diabetes patients who fail to achieve targets onmetformin or who have uncontrolled diabetes at the time of diagnosis to reducefuture cardio-renal complications. Patients' hearts will be at an advantage ifSGLT2 inhibitors are started early, before disease advances and not just as a3rd or 4th line of treatment.
For the patient, the new SGLT2 inhibitors are just like thehero in the movies, giving a punch to the villain while saving the heroine,hitting the sugar levels while protecting the heart! So let's give a cheer tothe new hero!