May 21, 2021—A primer on the use of pharmacotherapy and the emerging role of endoscopic interventions for the management of obesity was provided in a session given at Digestive Diseases Week, which took place online between May 21 and 23.
“There are several steps for obesity pharmacotherapy,” said presenter Shelby A. Sullivan, MD, of the University of Colorado School of Medicine and Anschutz Health and Wellness Center in Aurora, during her presentation. “Stop medications that can cause weight gain, identify patients who will benefit from weight loss medication, choose a weight loss medication that fits the patient, and determine if you should continue the weight loss medication.”
Classes of medication that are known to cause weight gain include several cardiovascular medications (beta-blockers and calcium channel blockers), anti-diabetes medications (insulin, thiazolidinediones, and sulfonylureas), steroids (prednisone and methylprednisolone), anticonvulsants, and the estrogen modulator tamoxifen. Psychiatric medications such as antidepressants (paroxetine, venlafaxine), almost all atypical antipsychotic drugs, and the mood stabilizer lithium are also among medications that can lead to weight gain.
Next, Dr. Sullivan outlined several characteristics of patients who can benefit most from weight loss medications. These include those who have a body mass index (BMI) ³ 30 kg/m2 or ³ 27 kg/m2 and at least one comorbidity associated with obesity who have not achieved weight loss with lifestyle therapy alone. Other patients who can benefit from pharmacotherapy include those who were unable to achieve targeted weight loss with endoscopic bariatric therapies or bariatric surgery, or those who have regained weight after losing weight following such interventions. “We have data to support the use of [medications] for all of these categories [of patients],” said Dr. Sullivan.
Research is available to help with treatment selection, although most pharmacotherapy is used off-label in obesity. A randomized study compared the combination of off-label phentermine/topiramate extended-release, phentermine alone, or topiramate alone for weight loss among obese adults. Both medications on their own led to significant weight loss, with ³ 5% total body weight loss occurring in 46.2% of patients in the phentermine arm and 48.6% of those in the topiramate arm. Similarly, 22.0% of patients in the phentermine arm and 25.0% of patients in the topiramate arm achieved ³ 10% total body weight loss. However, the results were most pronounced with the combination treatment: 66.0% of patients had ³ 5% total body weight loss, and 40.8% had ³ 10% total body weight loss.
Medications that successfully promote weight loss generally require a long-term approach. If side effects are absent or tolerable and weight loss is ³ 5% total body weight in 3 months, dose escalation is an option. If weight loss goals are not achieved with one medication, other medications can be considered.
In a retrospective study of nearly 14,000 patients, off-label use of phentermine showed the most significant reductions in total body weight loss with medium- and long-term use of 12- and 24-months’ duration, compared with 3 months. “This study also highlighted the importance of continuing the medications in only the responders because patients who responded to the medication had significantly more weight loss, on average, at 12 and 24 months, compared with patients who were not responders,” said Dr. Sullivan.
In a single-blind study that investigated long-term use of orlistat, patients regained almost all of the weight they had lost when they stopped taking it. Meanwhile, patients who were initially assigned to placebo lost significant weight after they started taking orlistat, once again highlighting the need to continue medication.
Across two different studies that investigated initiation of liraglutide or placebo following laparoscopic sleeve gastrectomy or endoscopic sleeve gastroplasty, significantly greater weight loss was observed in groups receiving liraglutide at 6 and 12 months.
The above studies also highlight the emerging role of surgical interventions, with or without concomitant medication, in weight loss. Currently, pharmacotherapy is a more common treatment than surgery, due to factors such as risk tolerance and balancing potential complications, despite prospective randomized trials showing the value of metabolic bariatric surgery. Shanu Kothari, MD, of Prisma Health in Greenville, emphasized the criticisms these trials have received, including lack of long-term follow-up or prospective design. “The takeaway is that metabolic bariatric surgery works four times more powerfully in the long term than pharmaceutical does in the potentially short term,” he said. “Pharmacotherapy clearly has a role, [but] endoscopic interventions are emerging, and they will have a place as well.”
Dr. Sullivan noted that, in the future, personalized medicine can help physicians determine which approaches will be effective for individual patients. Successful management of weight loss with pharmacotherapy is possible when the medication fits patients’ needs. One study demonstrated higher rates of weight loss at 12 months in patients who were assigned to treatment guided by their phenotype (ie, abnormal satiation, hedonic eating, abnormal satiety, or decreased metabolic rate), compared with those who received traditional treatment.
“If you can, you want to use a medication that can treat both obesity and another disease,” she said. “You also want to make sure there are no contraindications to the medication [and] that the patient is willing to stay on the medication in the long term. The cost of medications may not be covered by insurance, [so] patients need to be able to pay for them. Off-label medications may be less expensive out-of-pocket and should be considered.”