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Patients prescribed phentermine (Lomaira) or topiramate (Topamax) after Roux-en-Y gastric bypass (RYGB) were less likely to regain the weight they lost from surgery, according to a retrospective study.

Using three different statistical models, Nawfal Istfan, MD, PhD, of Boston University Medical School, and colleagues reported that cumulative weight regain decreased by approximately 10% (P=0.012) in patients taking the weight-loss medications compared with those who weren't.

Additionally, as shown in the team's study online in , the drugs reduced the statistical odds of weight-regain. In a Cox regression analysis, patients on these medications were found to be 27% less likely to experience significant weight regain (HR 0.73, 95% CI 0.56-0.96, P=0.023) compared with those who weren't. In a binary logistic model, the odds were reduced by 42% (OR 0.58, 95% CI 0.37-0.88, P=0.01).

Weight regain after RYGB and other bariatric procedures has become a well-recognized concern, the study authors noted. Previous retrospective studies have reported substantial weight regain and the re-emergence of obesity-related comorbidities post-surgery. In the current study, which included more than 700 patients, 50% regained at least one-third of the weight they had lost over 7 years of follow-up, the researchers said.

"Bariatric surgery is the most effective treatment strategy to combat obesity and achieve long-term resolution and/or improvement of most cardiometabolic dysfunction associated with it. However, as a chronic disease, obesity is subject to relapse years after bariatric surgery and it could require further medical interventions," the study authors wrote.

"Our study provides evidence that medications can help, especially in situations where the weight gain is occurring at a rapid rate," Istfan said in a statement.

The researchers analyzed the electronic medical records of 760 patients who underwent RYGB from 2004 through 2015 at Boston Medical Center. Of these, 350 (46%) were documented users of weight-loss drugs. Phentermine was prescribed to 119 patients (34%), topiramate was prescribed to 74 patients (21%), and 154 patients (44%) were given both. Only three patients (0.9%) were prescribed lorcaserin, and none were given generic or brand-name bupropion/naltrexone (Contrave) or brand-name phentermine/topiramate (Qsymia). Liraglutide 3.0 was not available at the time of the study.

No specific clinical parameters guided prescription of the weight-loss medications, the researchers noted, explaining that in most cases, the decision to take or withhold the medications was effectively a random event. "Therefore, to overcome this limitation, we used three independent statistical models, which consistently demonstrated that AOMs [anti-obesity medications] decrease cumulative weight regain by about 10% relative to nadir weight and reduce the odds of rapid weight regain after RYGB," the team wrote.

Istfan and co-authors compared patients' nadir weight (the lowest after surgery) with weight measured at postoperative office visits. In all, seven time intervals were used in the analyses: before surgery and at 1-2 years, 2-3 years, 3-4 years, 4-5 years, 5-6 years, and more than 6 years after surgery. The study took into account that patients started medications at different times and used them over variable and intermittent periods, the researchers noted.

Patients were categorized into quartiles based on the amount of weight regain. The highest quartile, in which patients regained as much as 41% of lost weight, was significantly more likely to include patients with type 2 diabetes (OR 1.69, 95% CI: 1.11-2.57, P=0.013) and patients who were prescribed weight-loss drugs but were prescribed the drugs but were nonadherent (OR 1.68, 95% CI: 1.04-2.56, P=0.033).

In an accompanying , Ricardo Cohen, MD, PhD, of the Oswaldo Cruz Hospital in São Paulo, Brazil, and David Cummings, MD, of the University of Washington in Seattle, said that options for addressing weight regain after bariatric surgery are limited -- including repair of postoperative complications, conversion into another operation, endoscopic therapies with inconsistent outcomes, and reintroduction of lifestyle-management counseling.

"Revision and conversion surgeries have higher complication rates than primary operations," Cohen and Cummings wrote. "Thus, pharmacological approaches may provide safer, effective strategies to mitigate insufficient weight loss and/or weight regain after bariatric/metabolic surgery. Nevertheless, there is no standard pharmacological regimen for that indication."

The editorialists noted that the only randomized, controlled trial of bariatric surgery with or without postoperative medication was the trial, which examined the effects of liraglutide 1.8 mg/d versus placebo in patients with type 2 diabetes at least 1 year after RYGB or sleeve gastrectomy. The primary endpoint was glycemic control, which was significantly better with liraglutide. However, the secondary outcome of weight loss was also better in that group. Participants taking liraglutide lost progressively more weight than did those taking placebo, ending with approximately 6 kg more total weight loss (P=0.017).

Other than GRAVITAS, studies of weight-loss medications used after bariatric surgery are scarce and primarily retrospective, the editorialists continued. "There is a compelling need for robust studies designed to provide level 1 evidence that better defines the role of pharmacological approaches to weight regain after bariatric/metabolic surgery."

Study limitations, Istfan and colleagues said, included the retrospective nature and the lack of a consistent protocol for prescribing weight-loss medications.

"The full potential of these agents and newer AOMs to counter weight recidivism and prevent the recurrence of obesity-related comorbidities needs to be further explored in prospective clinical trials," the researchers concluded. "Guidelines for initiating and monitoring the potential long-term use of AOMs after bariatric surgery need to be established."

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