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Weight loss medications may have a role after bariatric surgery



Is there a role for weight loss medications to help manage weight regain after bariatric surgery? Perhaps, according to a recent analysis of single-center clinical data.

Dr. Nawfal W. Istfan, Boston University

Dr. Nawfal W. Istfan

Phentermine and topiramate were each prescribed to between 10% and 12.5% of bariatric surgery patients at Boston Medical Center in recent years. That figure had been steadily increasing since 2004, when data collection began, Nawfal W. Istfan, MD, PhD, said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

However, the center didn’t know how patients who had received medication fared for long-term maintenance of weight loss, compared with those who had surgery alone; also, there were no clinical guidelines for prescribing weight loss medications (WLMs). “Have we done those patients any benefit by prescribing weight loss medications after gastric bypass surgery?” asked Dr. Istfan. The answer from the Boston Medical Center data is a qualified “yes;” patients with the highest rates of weight regain who were adherent to their medication did see lower rates of regain, and fewer rapid weight regain events.

Comparing patients who received prescriptions with those who did not, patients with less weight loss at nadir were more likely to receive a prescription. “This could very well be the reason they were prescribed a medication: They did not lose as much weight, and they are more likely to ask us” for WLMs, said Dr. Istfan, an endocrinologist at Boston University. However, for those who were prescribed WLMs, the slope of regain was flatter than for those who didn’t receive medication. Of the 626 patients included in the study, 91 received phentermine alone, 54 topiramate alone, and 113 were prescribed both phentermine and topiramate. Three received lorcaserin.

Those receiving medication were similar to the total bariatric surgery population in terms of age, sex, comorbidities, socioeconomic status, and preoperative body mass index, said Dr. Istfan, the senior author in the study. However, Hispanic individuals were more likely to receive WLMs, he said.

Recognizing that “the ratio of weight regain to nadir weight is more indicative of overfeeding than other parameters,” Dr. Istfan said that he and his colleagues divided patients into quartiles of regain, based on this ratio. The quartiles fell out so that those who had the least regain either lost weight or regained less than 1.4%, to make up the first quartile. The second quartile included those who regained from 1.5% to 6.26%, while the third quartile ranged up to 14.29% regain. Those who regained 14.3% or more were in the highest quartile of weight regain.

In comparing characteristics of the quartiles, there were more African Americans in the two higher quartiles (P = .017). More patients had achieved maximal weight loss in the highest quartile of regain (P less than .0001), though preoperative BMI had also been higher in this group (P = .0008).

After statistical adjustment, the investigators found that for individuals who had the highest quartile of regain, patients who were adherent to their WLMs had significantly less weight regain than those who took no medication (P = .014). However, patients considered nonadherent saw no medication effect on weight regain. The differences were small overall, with adherent patients regaining about 27% of weight relative to their nadir and those who didn’t take WLMs regaining about 30%. These significant results were seen long after bariatric surgery, at about 7 years post surgery.

In another analysis that looked just at the quartile of patients with the highest regain rate, weight regain was significantly delayed among those who were prescribed – and were adherent to – WLMs (P = .023). The analysis used a threshold weight regain rate of 1.22% per month; levels lower than that did not see a significant drug effect, and the effect was not seen for those not adherent to their WLMs.

Finally, an adjusted statistical analysis compared those taking and not taking WLMs to see whether WLMs were effective at preventing weight regain in rolling 90-day intervals throughout the study period. Again, in the highest quartile, those who were adherent to WLMs had a lower odds ratio of hitting the 1.22%/month regain rate, compared with those not taking medication (OR, 0.570; 95% confidence interval, 0.371-0.877; P = .01). The effect was not significant for the nonadherent group (OR, 0.872; 95% CI, 0.593-1.284; P = .489).

As more bariatric procedures are being done, and as more patients are living with their surgeries, physicians are seeing more weight regain, said Dr. Istfan, noting that it’s important to assess efficacy of WLMs in the postsurgical population. “Recent work showed that by 5 years after gastric bypass, half of patients had regained more than 15% of their nadir weight, and two-thirds of patients had regained more than 20% of their total maximum weight loss, said Dr. Istfan (King WC et al. JAMA.2018;320:1560).

Typically, patients will see about a 35% weight loss at their nadir, with a gradual increase in weight gain beginning about 2 years after surgery. Though it’s true that a net weight loss of 25% is still good, it can be a misleading way to look at the data, “because it does not focus on the process of weight regain itself,” said Dr. Istfan.

“Despite the maintenance of substantial weight loss, weight regain is concerning: It’s the present and future, not the past,” he said.

Regaining weight necessarily means that patients are having excess nutrient intake and a net-positive energy balance; this state can be associated with oxidative stress, inflammation, and insulin resistance – all potential contributors to the recurrence of comorbidities.

What’s to be done about weight regain, if it’s a point of concern? One option, said Dr. Istfan, is to consider more surgery. Patients might want a “re-do;” techniques that have been tried include reshaping the pouch and doing an anastomosis plication. If a gastro-gastric fistula’s developed, that can be corrected, he said.

Some factors influencing regain can be targeted by behavioral therapy. These include addressing alcohol consumption, discouraging grazing, encouraging exercise, and assessing and modifying diet quality in general.

“There is a general reluctance on the part of physicians to use weight loss medications after bariatric surgery,” said Dr. Istfan. Reasons can include concern about further nutritional compromise, especially when thinking about long-term use of appetite-suppressing medications. Importantly, there aren’t clinical guidelines for prescribing WLMs after bariatric surgery, nor is there a strong body of prospective studies in this area.

Dr. Istfan noted that the medical and surgical bariatric teams collaborate closely at Boston Medical Center to provide pre- and postoperative assessment and management.

The long observational interval and ethnic and socioeconomic diversity of the study population are strengths, said Dr. Istfan. Also, the three different multivariable models converged to similar findings.

However, the study was retrospective, with some confounding likely, and each prescriber involved in the study may have varying prescribing practices. Also, adherence was assessed by follow-up medication appointments, a measure that likely introduced some inaccuracy.

“Weight loss medications are potentially effective tools to counter weight regain after bariatric surgery; prospective studies are needed to optimize the use of weight loss medications after bariatric surgery,” said Dr. Istfan.

Dr. Istfan reported no outside sources of funding, and no conflicts of interest.

SOURCE: Anderson W et al. Obesity Week 2018, Abstract T-OR-2016.

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