Patient Presentation for Inadequate Weight Loss or Weight Recurrence and Anti-obesity Medications

| May 1, 2023

by Marina Kurian, MD, FACS, FASMBS, DABOM, DABS

Dr. Kurian is Director, New York Minimally Invasive Surgery, PLLC, and Clinical Professor of Surgery, NYU Langone Health in New York, New York.

Funding: This supplement was sponsored by Medtronic.

Disclosures: Dr. Kurian is a speaker for Vivus.

Bariatric Times. 2023;20(5–6 Suppl):S10–S11.

Key Points

  • Anti-obesity medications (AOMs) are an adjunct to surgery.
  • AOMs can be used in patients with inadequate weight loss or in patients with weight recurrence.
  • Patient history and health insurance coverage can direct to an appropriate AOM.

We are at a pivotal point in the treatment of obesity and severe obesity. In the United States (US), we have many medications to treat patients who are overweight with comorbid conditions, as well as those who have obesity with or without related conditions. At the same time, since obesity is a recurring disease, we are seeing patients with weight recurrence and assessing the possibilities for restorative or conversion procedures to aid in further weight loss. Patients post-bariatric surgery experience different trajectories,1 and we have all developed strategies to manage those patients who appear to be primary nonresponders or have inadequate weight loss. Dietary counseling and behavioral assessment underpin our efforts of getting both groups back on track. 

Historically, we have seen patients for weight recurrence and started a workup for anatomic issues, repointed dietary interventions, and might have started medications. For a more detailed analysis of what weight recurrence is, please see the American Society for Metabolic and Bariatric Surgery (ASMBS) POWER Task Force manuscript on this topic.2

Timing of intervention in the postoperative bariatric journey is not well researched. There are studies that show a benefit to adding medications at the first plateau versus treating weight recurrence when the patient presents to the surgeon.3 I personally have added medications at the first drop-off in the expected post-bariatric weight loss trajectory and have worked with obesity medicine specialists who resume medications early in the postoperative course, irrespective of weight loss. In addition, using multiple medications can provide enhanced weight loss in the post-bariatric surgery patient.4

The first assessment should be on the patient’s overall health, status of comorbid conditions, and type of bariatric surgery performed. Simultaneously, patients can start a workup for anatomic reasons for inadequate weight loss or weight recurrence and a dietary intervention. Once the patient is doing a closer follow-up with dietary guidance, medications can be discussed and tailored to the patient’s health conditions. Medications that are commonly used include phentermine and phentermine products, glucagon-like peptide-1 (GLP-1) receptor agonists, and combination medications, which include bupropion or topiramate. Most of these medications achieve 5- to 10-percent total weight loss (TWL) when used in the treatment of obesity. As with all medications, some patients are more sensitive to the side effects at different doses, and some patients are considered super responders and might see greater weight loss than 10-percent TWL. It is generally my strategy to increase the dose of medication only when I am not seeing the expected weight loss result. This decreases side effects and also slowly extends the use of the medication to higher doses, as patients can experience tolerance to certain medications.

Phentermine has been approved since 1959 for short-term use, and it is an indirect sympathomimetic that has an anorectic effect. Side effects, usually seen in higher doses, include jitteriness, palpitations, and insomnia. Phentermine comes in different doses, and it can be used long-term under the care of a physician.3

Topiramate was approved in 1998 for seizure disorder and then subsequently for the treatment of migraines. It has been used off-label for weight loss as well. Topiramate inhibits fructose 1,6-bisphosphatase and gluconeogenesis and has effects on neurotransmitters, hormones, and inhibition of carbonic anhydrase. The most common side effect is paresthesias and, in higher doses, a type of brain fog can occur where patients have trouble with word finding.5 

Phentermine/topiramate (Qsymia; VIVUS, LLC; Campbell, CA) was approved by the US Food and Drug Administration (FDA) as a combination product in July 2012 and is approved for long-term use. Several studies, including EQUIP6 and CONQUER,7 have shown five-percent TWL with the lower dose and 10-percent TWL with the higher dose. There are patients who are considered super responders and achieve 15- to 20-percent TWL. This medication is approved for long-term use in adolescents aged 12 to 17 years as well. There are only a few studies looking at phentermine/topiramate in post-bariatric surgery patients, and they experienced the expected greater than 10-percent TWL.8 The most common side effects include paresthesia, dizziness, constipation, insomnia, and dry mouth, and the effects are dose-dependent. Women of childbearing age need to be on birth control because of a slightly increased risk of cleft palate.9

Bupropion is an aminoketone antidepressant that inhibits norepinephrine and dopamine and is used off-label for weight loss. Bupropion combined with naltrexone (Contrave; Curax Pharmaceuticals, LLC; Brentwood, TN) was approved by the FDA in September 2014 for long-term weight loss. The exact mechanism of action is unknown; however, expected weight loss after one year is approximately 10-percent TWL. Bupropion/naltrexone has to be slowly titrated up to the maximum dose of two pills twice per day, and the most common side effects are nausea and constipation. This medication is not indicated for patients on long-term opioids or those undergoing surgery because of the naltrexone.10

GLP-1 receptor agonists promote insulin release, delay gastric emptying, reduce postprandial glucagon, and decrease food intake. GLP-1 receptor agonists were originally developed for treatment of Type 2 diabetes and resulted in significant weight loss. The half life of native GLP-1 is about two minutes, so GLP-1 receptor agonists, such as liraglutide (Saxenda; Novo Nordisk, Inc.; Plainsboro, NJ) and semaglutide (Wegovy; Novo Nordisk, Inc.; Plainsboro, NJ) activate the GLP-1 receptor for a greater duration of time. In the GRAVITAS trial, liraglutide was used for patients with persistent diabetes after Roux-en-Y gastric bypass or sleeve gastrectomy. The GRAVITAS trial showed an improvement in hemoglobin A1c as its primary outcome, as well as a greater than five-percent weight reduction in post-bariatric surgery patients. Both liraglutide and semaglutide are FDA approved in higher doses for the treatment of obesity in adults and adolescents aged 12 to 17 years.11 The most common side effects are nausea, vomiting, diarrhea, and constipation, which are mild to moderate in severity. Other side effects to consider are risk of pancreatitis and potential risk of thyroid cancer seen in animal studies; as such, it is contraindicated in patients with medullary thyroid cancer or history of MEN2 syndrome.12

Tirzepatide (Mounjaro; Eli Lilly and Company; Indianapolis, IN) is a once-weekly injectable peptide that is a glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist and is currently FDA-approved for the treatment of Type 2 diabetes. Tirzepatide has shown promising clinical results in Phase III trials, showing greater weight loss than other GLP-1 agonists, up to 22-percent TWL at higher doses. It is currently being evaluated for weight loss in higher doses and might be approved over the summer of 2023. 

There are other drugs in the pipeline, which include peptide tyrosine tyrosine (PYY) receptor agonists, as well as GLP-1 and glucagon receptor agonists. As studies are currently underway, we do not have a timeline for their approval.13 There are no studies of use of these medications in bariatric surgery patients, yet I am certain our patients will benefit from these medications as they become available.

References

  1. Voorwinde V, Hoekstra T, Monpellier V, Steenhuis I, et al. Five-year weight loss, physical activity, and eating style trajectories after bariatric surgery. Surg Obes Relat Dis. 2022;18(7):911–918.
  2. Majid SF, Davis MJ, Ajmal S, et al. Current state of the definition and terminology related to weight recurrence after metabolic surgery: review by the POWER Task Force of the American Society for Metabolic and Bariatric Surgery. Surg Obes Relat Dis. 2022;18(7):
    957–963.
  3. Redmond IP, Shukla AP, Aronne LJ. Use of weight loss medications in patients after bariatric surgery. Curr Obes Rep. 2021;10(2):81–89.
  4. Srivastava G, Buffington C. A specialized medical management program to address post-operative weight regain in bariatric patients. Obes Surg. 2018;28(8):2241–2246. 
  5. Stanford FC. Controversial issues: a practical guide to the use of weight loss medications after bariatric surgery for weight regain or inadequate weight loss. Surg Obes Relat Dis. 2019;15(1):128–132.
  6. Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). 2012;20(2):330–342. 
  7. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, Phase 3 trial. Lancet. 2011;377(9774):1341–1352. Erratum in: Lancet. 2011;377(9776):1494.
  8. Stanford FC, Alfaris N, Gomez G, et al. The utility of weight loss medications after bariatric surgery for weight regain or inadequate weight loss: a multi-center study. Surg Obes Relat Dis. 2017;13(3):491–500. 
  9. United States Food and Drug Administration. FDA Drug Safety Communication: Risk of oral clefts in children born to mothers taking Topamax (topiramate). Current as of 7 Feb 2018. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-risk-oral-clefts-children-born-mothers-taking-topamax-topiramate. Accessed 22 May 2023. 
  10. Greig SL, Keating GM. Naltrexone ER/bupropion ER: a review in obesity management. Drugs. 2015;75(11):1269–1280. 
  11. Miras AD, Pérez-Pevida B, Aldhwayan M, et al. Adjunctive liraglutide treatment in patients with persistent or recurrent type 2 diabetes after metabolic surgery (GRAVITAS): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019;7(7):
    549–559.
  12. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989–1002.
  13. Kokkinos A, Tsilingris D, le Roux CW, et al. Will medications that mimic gut hormones or target their receptors eventually replace bariatric surgery? Metabolism. 2019;100:153960. 

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