U.S. advisers neared a vote on whether a GlaxoSmithKline Plc diabetes drug carries too much heart risk to stay on the market, hearing final conflicting pleas Wednesday from a patient and a public health advocate.

The high-stakes recommendation by a panel of outside experts is designed to help the Food and Drug Administration settle a three-year safety dispute over Avandia.

Views on Avandia's risks are mixed within the FDA. Opinions also could be split within the 33-member panel of scientific experts after two days of hearing sharply conflicting opinions and reviewing hundreds of pages of data on whether Avandia causes heart attacks.

Avandia's U.S. sales were just 1.5 percent of Glaxo's 2009 revenues, but investors fear the company could face more lawsuits if the drug is pulled from the market.

Glaxo shares were up o.1 percent in London on Wednesday ahead of the vote, and were trading 1.1 percent higher in New York.

A 67-year-old diabetes patient, Chuck Keyserling, said he had taken Avandia for a decade with good results and argued that diabetics need the drug as an option to prevent serious complications, including heart disease, the leading killer of people with diabetes.

Please think about those of us who have flourished on Avandia and cannot take rival drug Actos, he told the advisers gathered in a hotel ballroom packed with spectators, journalists and several television cameras. For those people, a negative decision on Avandia may be a death sentence,

On the other side, the head of a research and advocacy group said enough evidence had stacked up against Avandia.

The data is so consistent that it's time to act, said Diana Zuckerman, president of the National Research Center for Women & Families.

On Tuesday, Glaxo agreed to pay $460 million to settle thousands of lawsuits over Avandia, Bloomberg reported, citing people familiar with the settlements.

Glaxo will settle about 10,000 suits for an average of $46,000 each, Bloomberg said. A Glaxo spokeswoman declined to comment. Plaintiffs' lawyers reached by Reuters also could not confirm a settlement.

The advisory panel is due to vote Wednesday afternoon on recommendations ranging from keeping the drug on the market with no warnings, to urging a withdrawal. Restrictions on use or beefing up warnings are among other choices.

Because the FDA asked panelists to select only one of the five options, there may be no clear majority. However, any vote short of withdrawal would back continued Avandia sales in some form.

In 2007, an advisory panel voted 20-3 that Avandia may increase the chances of a heart attack for some patients, but by 22-1 recommended that the drug stay on the market.

The agency will make the final call in the coming months but usually follows the advice of its panels.

On Wednesday morning, the committee also heard a plea from a Canadian researcher to continue a study aimed at providing a clearer answer on Avandia's heart risks. The trial called Tide is comparing the Glaxo drug to Takeda Pharmaceutical Co's Actos, which some FDA staff see as clearly safer.

Dr. Hertzel Gerstein, the study's lead researcher, said the panel could take the easy way by relying on less-reliable data of harm or insist on high quality evidence from large long-term trials such as Tide.

Critics say the Tide study is unethical because there is enough information now to conclude Avandia is dangerous rather than waiting years for results from Tide. The committee will consider later Wednesday if Tide should continue.

DIVIDED FDA

The debate on Avandia's safety has raged since warnings were placed on the drug in 2007 saying some research linked the drug to a higher heart attack risk but the data is inconclusive.

FDA staff are deeply divided over the safety of Avandia, also known as rosiglitazone, and the agency has thrown the issue to the expert panel to untangle.

Dr. David Graham, an FDA reviewer who has pushed for Avandia's withdrawal for years, said the agency applies different standards when deciding whether to approve a drug versus determining risk after a medicine is on the market.

Graham told the panel on Tuesday the Record study, relied on by Glaxo to show no increased heart attack risk from Avandia compared to older diabetes drugs, would not pass muster for an approval. You wouldn't even hear about it because it's garbage, he said.

Dr. Ellis Unger, a deputy director of drug evaluation, said he found Record's results pretty reassuring on heart safety.

But he added it was up to the expert panel to decide if Record was legitimate.

Glaxo officials defended Avandia before the advisers saying that, when used appropriately, the drug has a positive benefit/risk profile and should remain a treatment option.

For the FDA, the Avandia case is seen as a test of how the agency will handle major controversies under Democratic President Barack Obama. Officials are facing heavy pressure from consumer groups and some lawmakers who say the FDA fumbled decisions in past administrations and failed to protect the public.

(Reporting by Lisa Richwine; Editing by Tim Dobbyn)