Day one of the US Food and Drug Administration’s review on GlaxoSmithKline’s Avandia has seen the firm provide a staunch defence of the diabetes drug, reject accusations of withholding data and remain tight-lipped over reports that it is paying $460 million to settle a pile of lawsuits concerning the controversial treatment.

The FDA’s Endocrinologic and Metabolic Drugs and the Drug Safety and Risk Management advisory committee is halfway through its review of Avandia (rosiglitazone) focusing primarily on the cardiovascular safety of the drug. The agency’s commissioner, Margaret Hamburg, opened the proceedings and told the panel to “follow the science, wherever it leads, and the rest will fall into place” but the first day highlighted the difficulties the FDA is having in interpreting that science.

GSK then began its defence of Avandia and vice president for clinical development Murray Stewart insisted that when used appropriately, it has “a positive benefit/risk profile and should remain a treatment for type 2 diabetes”. After that critics of the treatment addressed the panel, notably Steven Nissen of the Cleveland Clinic who authored the 2007 meta0analysis which has led to this review.

Dr Nissen was particularly critical of the 4,427-patient RECORD trial, saying it was “unacceptable in quality”, a view echoed by Thomas Marciniak, medical team leader for the Division of Cardiovascular and Renal Products at the Center for Drug Evaluation and Research. However, Ellis Unger, deputy director at the Office of Drug Evaluation-I at the CDER’s Office of New Drugs, said that he found the RECORD data “pretty reassuring”.

Before the meeting began, however, attention was focused on claims by a former FDA official, Rosemary Johann-Liang, that GSK withheld from regulators a study showing Avandia may cause heart attacks. However, the company says the trial, referred to as Study 175, did not contribute any significant new information and related prinicipally to Takeda’s rival product Actos (pioglitazone) and was not about Avandia and heart attack.

Dr Johann-Liang’s claims were included in a letter sent by the US Senate Finance Committee to the FDA just as the review started and GSK said that “cherry-picking a handful of documents from more than 14 million pages of documents distorts the record and is misleading”.

Then, as day one drew to a close, Bloomberg reported that GSK had agreed to settle about 10,000 out of 13,000 Avandia lawsuits for $460 million. The company said it does not comment on ongoing litigation but the news agency quoted Gbola Amusa, an analyst at UBS, saying this is “exceptionally good news”.He said that “we had outlined an absolute worst-case scenario where $500,000 per case would have to be paid”.

The FDA advisory panel is due to vote later today on recommendations ranging from keeping Avandia on the market with no warnings, adding further warnings or urging a withdrawal.