Long-Term Weight Loss After Bariatric Surgery and the Role of PharmacotherapyApril 27, 2021
Achieving Weight Loss Long-Term: It has now been widely proven that bariatric surgery is the most effective and durable weight loss intervention, leading to significant improvement of obesity-associated health conditions, improvement in health-related quality of life, and an overall reduction in morbidity and mortality. (1, 2)
With the maturity of bariatric surgery as a specialty, new concerns have come regarding long-term outcomes. The issues of long-term suboptimal weight loss and weight regain after bariatric surgery are now at the forefront of the difficult problems being discussed.
Given the widespread practice of the two most common bariatric procedures, the Sleeve Gastrectomy (VSG), and the Roux-en-Y Gastric Bypass (RNY), the most available amount of data pertains to these two specific procedures.
Thanks to several well-respected publications, we have now established the average short-term weight loss after these 2 procedures to be at approximately 70% of excess weight lost at 2 years after an RNY and 60% after a VSG. (3)
Sub-Optimal Weight Loss
The first issue regarding post-surgery weight loss is the possibility of achieving Sub-Optimal Weight Loss (SWL), defined by many authors as ≤50% of Excess Weight Loss (EWL) at 1 year. Several reports quote anywhere between 5-20% of patients meeting these criteria, despite optimal surgical technique and regular follow-up. (5-7)
A large retrospective review showed that weight loss at the 3rd and 6th months was an independent predictor of maximal weight loss achieved by both VSG and RNY. This points towards the ability to identify this problem early and target therapy to improve outcomes.
There is also a growing issue of post-bariatric surgery patients who experience satisfactory weight loss, but then regain weight leading to re-appearance or worsening of obesity-associated medical comorbidities and patient dissatisfaction from the procedure.
Several studies have shown that a 5-10% of total weight loss regain can be expected within the first decade after bariatric surgery, with the highest weight being gained in the first year after the weight loss nadir in the post-RYGB patients. (2, 3, 8, 9).
The most widely accepted definition of problematic Weight Regain (WR) is regaining more than 25% of weight loss from the lowest recorded weight or gaining more than 5 BMI points from the BMI calculated at the lowest recorded weight. (10, 11)
A Multidisciplinary Approach
Management of post-bariatric surgery patients experiencing SWL or WR warrants a multidisciplinary approach, both to identify the potential causes of poor weight loss response as well as to formulate a multi-modal management approach.
The workup should include a thorough nutritional evaluation, behavioral assessment, a thorough medical evaluation with special emphasis on the patient’s medication list, and an anatomical evaluation via imaging and endoscopy; if warranted.
There are well-described anatomical abnormalities that lead to weight gain (gastro-gastric fistula, pouch dilatation, sleeve dilatation), but an increasingly recognized source of an iatrogenic weight gain are obesogenic medications. Several classes of medications have been very well associated with weight gain, including antihypertensives, antidiabetics, antidepressants, antipsychotics, antiepileptic and antihistaminic drugs. (12) These should be carefully reviewed and changed to alternatives if available.
The Role of Pharmacotherapy
Regardless, sometimes after a diligent evaluation, the actual causes are not identified. After anatomic, endocrine, and pharmacologic causes have been ruled out; the mechanisms responsible for SWL and WR after bariatric surgery remain poorly understood.
They are likely a combination of physiologic, behavioral, and psychological factors, and lifestyle and behavioral modifications alone can sometimes fail to yield satisfactory results. Traditionally, revisional surgery has been the mainstay of therapy in these cases, where an anatomical abnormality is corrected, or the initial bariatric procedure is converted to another one.
Although available data after revisional surgery is encouraging in terms of safety and weight loss success, complication rates are inherently higher. The decision for reoperation needs to be carefully studied on a case-by-case basis.
Sometimes there is no identifiable anatomic abnormality, the surgical risk is prohibitive, or the patient’s preference is through the non-operative route. In these cases, the role of “rescue” medical therapy has gained a great deal of interest.
Table 1 lists currently used anti-obesogenic medications for weight loss, along with their reported weight loss in treatment vs. placebo arms. It is worth mentioning that although all have been validated in multiple randomized controlled trials on obese patients without bariatric surgery, none have been officially FDA-approved for use in post-bariatric surgery patients. (13, 14, 15)
Nevertheless, the use of these anti-obesogenic medications is now becoming widespread in most high-volume bariatric centers around the country, and encouraging reports are now being published. (16) The most commonly used agents include Topiramate, Phentermine, Metformin, Bupropion, and Zonisamide.
For ease of administration, the medications exist both in individual formulations as well as in combination, but it must be mentioned that this pharmacotherapy must be strictly medically-supervised to ensure patient tolerance and avoid dangerous side-effects.
The choice of medication usually considers patient preference (injectable vs. oral), cost, and dual benefit (improving several coexisting conditions at once, such as diabetes, migraines, depression, tobacco use). Dosing is frequently started low and gradually increased based on patient tolerance. Currently, the indication for weight loss pharmacotherapy includes patients with a BMI ≥27 kg/m2 with at least one obesity-related comorbidity (hypertension, diabetes, hypercholesterolemia, and/or obstructive sleep apnea); or a BMI of ≥30 kg/m2 without comorbidities. (13, 14)
When reviewing the available data, one must be cautious to understand that most of these reports were created with the patients undergoing multiple interventions at once, including lifestyle modifications and exercise in addition to medications. This is important to underline, given that the best results will be obtained with this multimodal approach rather than medications on their own.
The largest study of pharmacotherapy after bariatric surgery enrolled 319 patients in 2 centers who underwent either a VSG or RYGB. More than half lost ≥5% of their weight, 30.1% lost ≥10% and 16% lost ≥15%. (17)
In this study, patients prescribed medications at their weight plateau rather than after weight regain had a small weight loss advantage compared to patients starting medication later. This suggests that pharmacotherapy could potentially be considered earlier postoperatively.
Weight Loss Long-Term Summary
In conclusion, with the maturity of bariatric surgery, long-term outcomes and challenges are now arising and generating important conversations. Of these challenges, suboptimal weight loss and weight regain after bariatric surgery is amongst the most widely discussed topics.
These patients must be thoroughly studied to identify and correct any potential causes. Aside from surgical correction of well-described anatomical issues, pharmacotherapy is garnering a very important role in the management of these patients.
The use of weight-loss medications in addition to lifestyle modifications is showing great promise in enhancing or correcting weight loss after surgery, and this treatment modality might even show greater benefit if started earlier in the postoperative period.
The timely identification of problems and multimodal approach underlines yet another reason why appropriate follow-up at an experienced and well-established bariatric center is absolutely necessary for the success of successful weight loss long-term.
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- Sjostrom L. Review of the key results from the Swedish obese subjects (SOS) trial - a pro- spective controlled intervention study of bariatric surgery. J Intern Med. 2013;273(3):219–34.
- Buchwald, H., Avidor, Y., Braunwald, E., Jensen, M. D., Pories, W., Fahrbach, K., & Schoelles, K. (2004). Bariatric surgery: a systematic review and meta-analysis. Jama, 292(14), 1724-1737.
- Lauti M, Kularatna M, Hill AG, MacCormick AD. Weight regain following sleeve gastrec- tomy-a systematic review. Obes Surg. 2016;26(6):1326–34.
- de Raaff CA, Coblijn UK, de Vries N, Heymans MW, van den Berg BT, van Tets WF, van Wagensveld BA. Predictive factors for insufficient weight loss after bariatric surgery: does obstructive sleep apnea influence weight loss? Obes Surg. 2016;26(5):1048–56.
- Livhits M, Mercado C, Yermilov I, Parikh JA, Dutson E, Mehran A, Ko CY, Gibbons MM. Preoperative predictors of weight loss following bariatric surgery: systematic review. Obes Surg. 2012;22(1):70–89.
- Perugini RA, Mason R, Czerniach DR, Novitsky YW, Baker S, Litwin DE, Kelly JJ. Predictors of complication and suboptimal weight loss after laparoscopic roux-en-Y gastric bypass: a series of 188 patients. Arch Surg. 2003;138(5):541–5; discussion 5-6.
- Adams TD, Davidson LE, Litwin SE, Kim J, Kolotkin RL, Nanjee MN, Gutierrez JM, Frogley SJ, Ibele AR, Brinton EA, Hopkins PN, McKinlay R, Simper SC, Hunt SC. Weight and meta- bolic outcomes 12 years after gastric bypass. N Engl J Med. 2017;377(12):1143–55.
- Magro DO, Geloneze B, Delfini R, Pareja BC, Callejas F, Pareja JC. Long-term weight regain after gastric bypass: a 5-year prospective study. Obes Surg. 2008;18(6):648–51.
- Baig SJ, Priya P, Mahawar KK, et al. Indian bariatric surgery outcome reporting G. weight regain after bariatric surgery-a multicentre study of 9617 patients from Indian bariatric surgery outcome reporting group. Obes Surg. 2019;29:1583–92.
- Lauti M, Lemanu D, Zeng ISL, et al. Definition determines weight regain outcomes after sleeve gastrectomy. Surg Obes Relat Dis. 2017;13:1123–9.
- Leggett CB, Desalermos A, Brown SD, Lee E, Proudfoot JA, Horgan S, Gupta S, Grunvald E, Ho SB, Zarrinpar A. The effects of provider-prescribed obesogenic drugs on post- laparoscopic sleeve gastrectomy outcomes: a retrospective cohort study. Int J Obes (Lond). 2019;43(6):1154–63.
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- Alverdy, J., & Vigneswaran, Y. Difficult Decisions in Bariatric Surgery. Pannain S. Ch 30: Suboptimal Weight Loss and Weight Regain: Is it Prime Time for Pharmacotherapy? Springer International Publishing AG. 2020; 339-354
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ABOUT THE AUTHORAlvaro Galvez MD, specializes in laparoscopic and robotic surgery, with a focus on bariatric and foregut surgery at AtlantiCare Regional Medical Center. Using minimally invasive techniques, his goal is to provide care designed to minimize the impact of surgery and ensure the quickest postoperative recovery time. Additionally, Dr. Galvez is a well-published author and presenter in national and international conferences on the topics of weight loss and minimally invasive surgery.