FDA Advisory Split on Sibutramine

As readers will recall, yesterday, I presented at an FDA Advisory on sibutramine.

In the end, the Advisory Committee was split over whether the weight loss drug sibutramine (Meridia) should be pulled from the market or not.

Eight members of the panel voted that sibutramine should remain on the market, with certain new restrictions, while eight members voted that patients on the drug don’t lose enough weight to make it worth the potential cardiovascular risk.

Although the adivisors were largely appreciative of the design of the SCOUT study, they did note that extrapolation of these data to the “real-world” use of this drug is difficult.

Thus, when the Advisors were specifically asked how they would relate the SCOUT data, including the post-hoc subgoup analyses, to the use of sibutramine in subjects without a history of cardiovascular disease, the advisors raised several issues including the lack of power, lack of statistical evidence for interaction and other issues that limit interpretation of the SCOUT data. However, concern was raised about the upper boundaries of the risk estimates, even in the diabetes only group – the group with the lowest CV risk and the group perhaps closest to the “on-label” population.

There was also concern about increased heart rate, especially as a sub-analyses presented at this meeting, suggested that a heart rate over 90 bpm was an important predictor of outcomes.

Regarding whether or not the risk of taking sibutramine can be mitigated by monitoring of blood pressure and pulse, the advisors were not convinced that monitoring these vital signs alone would fully address the issue of possible increased risk.

In addition, advisors challenged the notion that screening for occult cardiovascular disease would be practical or accurate enough to identify patients at risk. This would also hardly be a cost-effective approach to deciding for whom sibutramine would be safe and for whom not. Other advisors disagreed, and thought that monitoring of vital signs may well be a reasonable solution to address this issue.

Regarding whether the risk can be mitigated by monitoring body weight, i.e. not continuing sibutramine in subjects who do not lose at least 5% of their body weight during the first 3 months of treatment, several advisors felt that this was probably a better way to mitigate risk than just monitoring vital signs. However, the objection to this was that assessing weight-loss response, would of course require exposing patients to the drug for at least three months.

Regarding the potential risks and benefits of the use of sibutramine in overweight and obese individuals, many advisors did not think that a strong enough case was made for benefit.

One advisor pointed out that weight loss in itself has a value, particularly in terms of motivating patients to make lifestyle changes.

Nevertheless most advisors did not appear convinced of any real benefit and looked at weight loss more as a surrogate outcome.

As some advisors noted, it appears that although sibutramine may deliver on the weight loss, it is not clear that it actually delivers on benefits. Others disagreed and felt that weight loss itself was a meaningful and important benefit.

For me, the experience of presenting the case for obesity treatment at this FDA hearing was a welcome opportunity to present my own views on the importance of addressing this important health problem.

After all, there is no doubt that the future of our health care systems will eventually depend on whether or not we effectively manage to treat obesity in the millions of people who are already struggling with the devastating consequences of excess weight.

Given the limited pharmacological options for managing obesity, I do hope that the FDA will ultimately decide to continue making this drug available for those patients, who can potentially benefit.

Cambridge, UK

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Disclosure: I have received consulting and speaking honoraria from Abbott Laboratories, the makers of sibutramine.