New data has suggested that long-term usage of phentermine to lose weight appears to be safe and effective.
Findings from an analysis of the electronic records of around 14,000 adult phentermine users were presented in a late-breaking session on November 14, 2018 as part of Obesity Week. The information was presented by Kristina H. Lewis, MD, of the Wake Forest University Health Sciences in North Carolina.
Phentermine is a generic appetite suppressant that received approval by the United States Food and Drug Administration (FDA) in 1959. It is considered to be a short-term adjunct – intended to be used for a few weeks – for weight loss. There are some concerns about the long-term use of phentermine, including the potential for addiction and cardiovascular problems.
Phentermine is among the most used weight loss medications in the United States, but it is currently intended for short-term use. This isn’t in keeping with the idea that obesity is a long-term chronic condition that requires long-term solutions. As a generic drug, there wasn’t much incentive to undertake long-term studies on phentermine.
In 2012, a combination drug of phentermine and topiramate (Qysmia, Vivus) was approved based on data that showed it could be used safely and effectively for up to two years. This prompted Lewis and her team to attempt to collect similar data on phentermine by itself. Lewis talked to Medscape Medical News, explaining that no one had taken the time to look at phentermine by itself so she attempted to do it with her team.
There is some value to this research, as many insurers will only cover phentermine by itself and won’t cover the branded combination, which is understandably more expensive. When considering the epidemiology of obesity and who it is affecting, it becomes clear that there is a need for affordable drugs to be made available to low-income patients.
While Lewis’ data shows that long-term use of phentermine presented significantly more weight loss compared to short-term use, and without a noticeable increase in cardiovascular disease or death, she took the time warn that her analysis is by no means complete. Lewis explains that there is still a need for clinical trials that take a deeper look.
When asked to comment, Stephen R. Smith, MD, Chief Scientific Officer at Florida Hospital Research Services said that the study made for a good preliminary study. He said it should give physicians more confidence as there is extra data out there now. He was quick to add that while the study was large, it was also under-powered. It was unable to detect a safety signal. He did at least note that there were enough people involved in the study to suggest there is nothing there to worry about.
His conclusion was that the population needs to be sick enough to get clear results. The participants in the study were predominately healthy female middle-aged adults; a representation of the people likely to take phentermine. The study is a nice start, despite being inconclusive for the general population.
Using Phentermine for Longer Associated with More Weight Lost
Lewis and her colleagues used the electronic health records from eight systems that are part of the Patient Outcomes Research for Advanced Learning cohort. This includes Kaiser sites in 7 regions in the US as well as Denver Health and Health Partners. The study took place between January 2010 and September 2015.
The participants in the study included 13,972 adults with a body mass index of greater than 27kg/m2 (the average was 37.2 kg/m2) and a first phentermine prescription fill during the time of the study. 84% of participants were women, 45% of them were white, and they had a mean average age of 43.5 years. The rates of comorbidities were relatively low and the study included people with hypertension (21%) and diabetes (12%), and 34% of participants were smokers or former smokers.
The participants in the study were separated into five groups based on their exposure to phentermine;
- Per label-short term users (referent) that had used phentermine once for less than three months (6,764 participants)
- Short-term intermittent users that had used phentermine several times, each time less than three months (2,938 participants)
- Medium-term continuous users that had used phentermine several times, with at least one episode lasting longer than 3 months but less than 12 (1,703 participants)
- Medium-term intermittent users who used phentermine several times, including at least one episode that lasted between 3 and 12 months (2,423 participants)
- Long-term continuous users that had used phentermine for longer than 12 months at least once (144 participants)
When adjusting for race/ethnicity, sex, age group, BMI, comorbidities, and other variations between participants, the estimated weight loss for six months use was already significantly greater for those who would continue to use phtermine.
After 12 months, some of the referent group had begun to put weight back on, the medium-term group regained less weight, and the long-term continuous group maintained a weight loss of around 7%.
By 24 months, the long-term group had managed to regain most of the weight they had lost, while the other groups had maintained a significantly higher weight loss by comparison; 0.4%, 1.9%, 3.6%, and 7.5% for the short-term intermittent, medium-term continuous, medium-term intermittent, and long-term continuous groups respectively.
To account for the idea that those who continued to use phentermine were likely to be the people that it worked best for from the beginning, the investigators also performed a sensitivity analysis that looked at just those who showed an initial reaction to the drug. The results for this were similar, but stronger; ranging from a 6.3% weight loss for the referent group to 8.5% weight loss for long-term continuous users after six months.
By 24 months, the referent group regained around half of their weight loss, but the long-term continuous group continued to lose more, averaging a weight loss of 10.7%.
No Cardiovascular Risk After 2 Years of Phentermine Use
The overall composite safety outcome of incidents of myocardial infraction, cardiovascular intervention, stroke, or death was rare. Only 0.3% of the 13,972 participants (41) were affected by these issues.
Compared to the short-term group, the hazard ratio was 0.72 for both short-term and medium-term intermittent groups. It was 1.54 for the combined medium-and-long-term continuous groups. These two groups were combined as there were no events for the long-term continuous group. None of these differences proved to be significant.
The 0.3% event rate for the phentermine study was lower than the average 1-1.5% seen with the majority of big cardiovascular outcomes studies. It should be noted that the sample size for the trial was possibly under-powered to determine small increases in risk though, but the study is a great starting point for something larger.
While it’s true that there isn’t much incentive for those in the industry to fund a larger study on a generic drug like phentermine, government entities such as the Centers for Medicare and Medical Services or the National Institutes of Health should put down the money. There is a gap in knowledge about phentermine and, given how many people are using phentermine, there is definitely a public interest in knowing about the long-term effects.
This particular study was funded by the Patient-Centered Outcomes Research Institute and Lewis has reported receiving research funding from Nestle, but says it was unrelated to this study.
Original article can be found here.