Doctors get good and bad safety news on diabetes drugs

By Ben Hirschler

AMSTERDAM (Reuters) - Diabetes pills known as DPP-4 therapies got a mixed safety report on Monday as studies showed they did not raise the risk of heart attacks but might be linked to heart failure, where the heart fails to pump blood adequately.

Reassuringly, the medicines were not associated with increased rates of either inflammation of the pancreas or cancer - something that has been a worry in the past.

However, in the case of AstraZeneca and Bristol-Myers Squibb's approved drug Onglyza, there was a small increase in hospitalisations for heart failure.

"It is a little bit concerning," said Dr. Christopher Grainger of Duke University Medical Center, who was not involved in the research. "I'm sure the FDA (U.S. Food and Drug Administration) will want to know more about it."

Citigroup analyst Andrew Baum, who forecasts Onglyza sales of $2.47 billion in 2018, said the latest data would not ameliorate growing pressures on the DPP-4 drug class in terms of winning reimbursement and achieving wider use.

Doctors and regulators are wary of the cardiovascular safety profile of diabetes drugs following past problems, including with GlaxoSmithKline's Avandia pill, since patients with diabetes are at increased risk of heart troubles.

Researchers from Brigham and Women's Hospital in Boston, who studied Onglyza over two years in 16,492 patients, said the heart failure finding was unexpected and deserved further investigation.

AstraZeneca and Bristol had already given headline results from the study in June, showing Onglyza did not increase heart attack risk - although it did not reduce it either, as the companies had initially hoped.

To date, researchers have been unable to identify any diabetes drug that is not only safe but actually beneficial to the heart.

Some doctors were disappointed that Onglyza and Takeda's <4502.T> rival drug Nesina did not reduce heart risks. However, Dr. Heinz Drexel, a heart specialist at Feldkirch Hospital in Austria and a spokesman for the European Society of Cardiology (ESC), said the idea of such a benefit from taking the medicines was "not logical".

Drexel said DPP-4s still offered several advantages, including a lack of weight gain seen with some other antidiabetics, which would offset the heart failure worries.

NO OVERALL INCREASE

Detailed results of the Onglyza study were presented at the ESC annual congress in Amsterdam, alongside a 5,380-patient study of Nesina. Both studies showing no overall increase in cardiovascular risks were published simultaneously in the New England Journal of Medicine.

The co-principal investigator on the Onglyza study, Dr. Deepak Bhatt, said he believed the heart failure issue seen with Onglyza was very likely a class effect common to all DPP-4s, adding it had probably not shown up in the Nesina trial because it was far smaller.

Still, he said the increase in heart-failure hospitalisations with Onglyza was small, affecting 3.5 percent of those taking the drug compared with 2.8 percent for the control group.

Dr. Anthony DeMaria, editor-in-chief of the Journal of the American College of Cardiology, said the absence of severe adverse events was reassuring but it might be that DPP-4s were best avoided for certain patients at high risk of heart failure.

Drugs like Onglyza and Nesina work by inhibiting dipeptidyl peptidase-4, or DPP-4, to enhance the body's ability to lower elevated levels of blood sugar.

DDP-4s are not the most powerful agents for lowering blood sugar levels but they are well tolerated and have proved an attractive option for doctors looking for new oral drugs.

The DPP-4 market is dominated by Merck's Januvia, which has annual sales of around $5 billion, including a related combination treatment called Janumet. But growth of the class has slowed this year, partly on concerns over pancreatic safety.

Onglyza, which had sales of $709 million in 2012, is a crucial product for AstraZeneca, which is banking on diabetes to help revive falling group sales due to patent expiries on several of its biggest-selling drugs.

Briggs Morrison, AstraZeneca's head of global medicines development, said the overall results of the latest trial were reassuring and the small increase in heart failure hospitalisations did not change the risk profile of the drug.

A similar heart study of Merck's Januvia in more than 14,000 patients is being conducted with results expected next year. (Editing by Jason Neely and David Holmes)

Matches

MORE TOP STORIES TODAY

Pietersen may play against Hyderabad

Pietersen may play against Hyderabad

As much as Pietersen's availability is a boost, the loss of a potent death bowler might sting Delhi badly. More »

Bangalore lose nerve, lose game

Bangalore lose nerve, lose game

IPL 7, GAME 11—Vinay's over, Lynn's catch turns last-over finish in KKR's favour. More »

Struggling Mumbai need batting fuel

Struggling Mumbai need batting fuel

Mumbai have explosive hitters down the order in the form of Corey Anderson and Kieron Pollard, but the lack of contributions from them has compounded their… More »

Boycotting IPL will not save cricket

Boycotting IPL will not save cricket

Boycotting the IPL as a means of protest against the grime in the game may not yield the desired results. More »

Srinivasan's ICC presence to be challenged

Srinivasan's ICC presence to be challenged

Srinivasan, who has been replaced by the court as board president, was named the BCCI's representative to the ICC last September. However, that position… More »

Atapattu tipped to coach Sri Lanka in England

Atapattu tipped to coach Sri Lanka in England

Sri Lanka's chief selector Sanath Jayasuriya issued the strongest indication yet that Marvan Atapattu would be appointed coach for the tour of Ireland… More »

Couldn't turn down ECB offer: Farbrace

Couldn't turn down ECB offer: Farbrace

England's new assistant coach Paul Farbrace admitted that it was impossible turn down the job even though he will have mixed feelings when he faces… More »

Cleaning up the game starts with fans

Cleaning up the game starts with fans

... because, as recent events reveal, the BCCI has little intention of doing it. More »

'BCCI should have picked panel with care'

'BCCI should have picked panel with care'

Dalmiya said that it was the first time that the BCCI had been faced with a situation where the apex court had hauled up the Board and it should have acted… More »

Jadeja spins out Rajasthan in close chase

Jadeja spins out Rajasthan in close chase

IPL 7, GAME 10—Chennai beat Rajasthan by 7 runs after last-over scare. More »

Is Srini group delaying BCCI meeting?

Is Srini group delaying BCCI meeting?

The group opposed to Srinivasan alleged that since BCCI secretary Sanjay Patel belongs to the president’s group, he was intentionally delaying the SGM… More »

Vithanage, Priyanjan get T20 call-ups

Vithanage, Priyanjan get T20 call-ups

Herath has been rested, while the team will be without the veteran pair of Mahela Jayawardene and Kumar Sangakkara, who retired from T20 internationals… More »

'Gambhir will strike form soon'

'Gambhir will strike form soon'

Gautam made an eight-ball duck in the opening game against Mumbai and in the second game against Delhi, he lasted only half those balls. More »

SL in 'difficult place' after Farbrace exit

SL in 'difficult place' after Farbrace exit

Sri Lanka depart for assignments in Ireland and England in two weeks, and Sanath Jayasuriya suggested Marvan Atapattu would be interim head coach for those… More »

Chandimal axed as T20 captain

Chandimal axed as T20 captain

Sri Lanka's cricket selectors on Wednesday sacked Dinesh Chandimal as Twenty20 captain and replaced him with Lasith Malinga, while Angelo Mathews was… More »

Farbrace is England's assistant coach

Farbrace is England's assistant coach

The ECB continued the restructuring of the England coaching set-up on Wednesday by announcing the appointment of Paul Farbrace as assistant coach. More »

SC asks Mudgal committee to continue

SC asks Mudgal committee to continue

Mukul Mudgal has communicated to the court his willingness to take up the investigation and has been asked to specify the terms and modalities on April… More »

Sri Lanka players resolve pay dispute

Sri Lanka players resolve pay dispute

The pay dispute between Sri Lanka Cricket and its 13 contracted players ended on Wednesday when the latter agreed to accept 10 percent of the participation… More »

Hope to be fit for next game - Pietersen

Hope to be fit for next game - Pietersen

With two heavy defeats at the hands of Bangalore and Chennai, Daredevils currently languish near the bottom of the table. More »

'SC decision could hurt BCCI's status'

'SC decision could hurt BCCI's status'

The Supreme Court prefers that the Justice Mudgal panel further investigate the IPL corruption scandal. More »

Mudgal panel drops bombshell in court

Mudgal panel drops bombshell in court

The Mukul Mudgal probe committee dropped a bombshell in the Supreme Court on Tuesday by making a sensational claim that it was forced to stop audio recording… More »

Perfect Punjab trounce Hyderabad

Perfect Punjab trounce Hyderabad

IPL7, GAME 9—Maxwell (95, 43b), Balaji (4-13) set up 72-run win. More »

Have the ECB played an unfair game?

Have the ECB played an unfair game?

Money talks, but it is in light of this ICC shakeup that the ECB's act of soliciting of another team's coach deteriorates from free-market aggression to… More »

Farbrace quits for England post

Farbrace quits for England post

He will assist Peter Moores who was unveiled as the new England coach on Saturday. More »