GlaxoSmithKline has agreed in principle to settle its most significant disputes with the US government over the way it marketed and developed its drugs, at a cost of €2.2 billion, which is covered by existing provisions.

The settlement, over both civil and criminal claims, is expected to be finalised in 2012. It includes a department of justice investigation into the company's controversial diabetes drug Avandia, which has been linked to heart risks.

Britain's biggest drugmaker already took massive charges last year related to liability claims from patients who had been taking Avandia.

The company's current legal provisions are £2.9 billion pounds (€3.36 billion).

The deal to resolve the latest disputes follows a clampdown in the United States on unfair pharmaceutical industry practices that has forced major drugmakers to rethink the way they do business in the world's biggest market.

Since the late 1990s the number of industry settlements with U.S. states and the federal government has soared as authorities have taken an increasingly tough line on practices that may have put commercial goals above the interests of payers and patients, such as marketing drugs for unapproved uses.

Announcing the outline settlement today, GSK said it had implemented fundamental changes to US selling procedures in recent years and chief executive Andrew Witty said the cases "do not reflect the company that we are today".

Changes under Mr Witty's watch include a new bonus system for US sales representatives, who no longer work to individual sales targets. Mr Witty has also overhauled the group's top US management.