FDA Warns of Heart Failure Risk With Two Di... - Diabetes India

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FDA Warns of Heart Failure Risk With Two Diabetes Drugs

The US Food and Drug Administration (FDA) has issued a new alert about the potential for increased risk for heart failure in patients taking the type 2 diabetes drugs saxagliptin (Onglyza, AstraZeneca Pharmaceuticals LP) and alogliptin (Nesina, Takeda Pharmaceuticals).

The FDA announced that new warnings will be added to the labels of the two dipeptidyl peptidase–4 (DPP-4) inhibitor drugs, cautioning that they may increase the risk for heart failure, particularly in patients who already have cardiovascular or kidney disease.

"Health care professionals should consider discontinuing medications containing saxagliptin and alogliptin in patients who develop heart failure and monitor their diabetes control," an FDA statement notes. "If a patient's blood sugar level is not well-controlled with their current treatment, other diabetes medicines may be required."

Combination products containing the two agents are also affected, including saxagliptin and metformin extended release (Kombiglyze XR, AstraZeneca Pharmaceuticals LP), alogliptin and metformin (Kazano, Takeda Pharmaceuticals), and alogliptin and pioglitazone (Oseni, Takeda Pharmaceuticals).

The move follows an FDA internal safety review of two large cardiovascular outcomes trials of patients with cardiovascular disease and a recommendation for the label revision by the FDA's Endocrinologic and Metabolic Drugs Advisory Committee during an April 2015 hearing.

At that meeting, the panel expressed greater concern about heart failure for saxagliptin than for alogliptin, but because the mechanism is not clear and the two belong to the same class, the majority opted to recommend the warning on both labels.

Results of the two studies — Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) and Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) — were first presented at the European Society of Cardiology meeting in 2013 and later published in the New England Journal of Medicine.

In the saxagliptin trial, which included 16,492 patients with type 2 diabetes and established cardiovascular disease or who were at high risk for cardiovascular disease, there was no overall risk for cardiovascular events, but there was a 27% increase (3.5% vs. 2.8%) in the rate of the first event of hospitalization for heart failure and a potential increased risk for all-cause mortality. Risk factors included a history of heart failure or kidney impairment.

In EXAMINE, which included a total of 5380 patients, 3.9% of patients receiving drug were hospitalized for heart failure vs 3.3% of patients receiving placebo. Although the difference was not statistically significant (hazard ratio, 1.19), heart failure was not an endpoint of the study.

11 Replies
cure profile image

What is exact pathway??? if merck paid more??? or AstraZeneca failed to pay???

in reply to cure

No idea 

cure profile image
cureAdministrator in reply to

sure we will never know...and we can always say.....'Mechanism is not clear and the two belong to the same class'.......

And we will show our great concern......LOL

patliputra profile image
patliputra in reply to cure

Good point.

cure profile image

Thanx sir.....after the news of Januvia missed sales targets....Things are getting more and more interesting now.....

This is same like after expiry of patent period of statin...all bad things about statin started pouring in.....

in reply to cure


Missing sales targets is an indication of: 1) Irrational targets set it. 2) more new patients being put on other DPP4 

It in no way indicates that the drug usage has come down 

Anyway that's how it is 

Newer molecules comes with some advantages and newer patients are put on it 

But this risk of HF lies with all the molecules of this class

So we need to control thru diet rather than meds

Unfortunately many pts wants to enjoy food and life and want to continue the existing harmful diet and willing to pop few pills 

So in this scenario all are happy and the pts pays it later in life with adverse effects with cost burden 

cure profile image
cureAdministrator in reply to

Very true.....all drugs are for 'LIFE STYLE IMPROVEMENT' this means with popping pills you can enjoy what you were doing earlier....

Mr Mike always say...stop doing what you were doing and you won't get what you have got...

But ppl still wants to pop pills and keep doing same thing....and at last pay for they do to the body...

Human body is very very complex ... there are many complex chemical reactions taking place in body...with minimum intervention one must try to balance his body.

Drugs are of course beneficial....but as last resort....not as first line of action.

Yes. And who pays? 

The patients 

With health and money 

And many goes laughing to the bank

The misery continues... 

So the risk lies with all the DPP4 irrespective of what's said or proved 

cure profile image

Further.....missing sales targets means raise of competition...new entrants in market....losing 'MARKET SHARE'

In marketing  increase in sales or decrease in numbers does not hurt the company.....but what it hurts more is losing the market share...

New entrants  eat in to market share of established company...

And then established company makes move to kill competitor....

Many thanks for the information. Metformin included!! We must go for drug-free diabetic control (or cure).

in reply to RSNGR


But metformin has been here for donkeys years 

So relatively safer than these newer drugs 

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