The effectiveness and safety of pharmaceuticals to manage excess weight post-bariatric surgery: a systematic literature review

Figures & data

Figure 1. PRISMA Flow-chart.

Table 1. Characteristics of studies which met inclusion.

Author	Population Characteristics	Study Type	Type of Bariatric Surgery	Duration	Weight Management Medication	Treatment initiation in relation to the surgery; Indication for initiating the weight loss medication	Weight Effect
Gorgojo-Martinez (2016)^15	164 M/F BMI: Bariatric surgery patients 40.3 ± 9.2 kg/m^2,; Non-bariatric surgery patients 39.7 ± 7.6 kg/m^2Mean age 53.0 ± 9.0 years	Retrospective cohort	RNY (53.3%), BPD (20%), Vertical Gastric Banding (13.3%), SG (6.7%) and AGB (6.7%)	104 weeks	Liraglutide 1.8mg	ND Failure to lose weight in the previous year despite a structured lifestyle program. A weight gain of >5% of the minimum weight reached post bariatric surgery was considered relevant	There were similar significant decreases in weight for the subjects who had bariatric surgery (3.4kg, p =.011) and those who did not (2.3kg, p =.011).
Guerdjikova (2005)^18	3 F 44–55 years 35.3 kg/m^2	Case series	RNY	4 to 17 months (mean: 30 months)	Topiramate	14-30 months post-surgery Return of binge eating and weight regain (5-20 kg).	All patients lost weight (range: 2 to 31.7kg, mean: 16.1 kg, P-value NR).
Nor Hanipah (2018)^13	209 M/F BMI: NR Mean age: 50.9 ± 10.5 years	Retrospective cohort	RNY (60.3%), SG (24.9%), ABG (10.0%), Gastric plication (1.9%), and revisional surgery (2.9%)	3 months to 12 months	Phentermine, phentermine/topiramate, lorcaserin, naltrexone/bupropion	Median time of 38 months (interquartile range, 24-63) Weight regain (>5% nadir) or poor weight loss (<50% excess weight loss) after bariatric surgery.	Patients lost 3.2% of their body weight by 3 months and 2.4% by 12 months (P-value NR). Patients with AGB (4.6%) and RNY (2.8%) lost significantly more weight than those with SG (0.3%, p≤.02).
Jester (1996)^11	34 M/F BMI: 34.0 kg/m^2Age range: 27-65 years	Retrospective cohort	RNY (35.3%), and BPD (64.7%)	12 weeks	Phentermine and fenfluramine as a monotherapy or in combination	≥18 months post-operative ≥9 kg above ideal body weight	All patients lost weight (4.5 to 22.7 kg, P-value NR). RNY lost on average 11.4 kg and BDP 11.8 kg (P-value NR).
Pajecki (2012)^12	15 M/F BMI: 42.4 kg/m^2Mean age: 47.2 ± 12.5 years	Retrospective cohort	AGB (26.6%), RNY (60.0%), Duodenal switch BPD (6.7%), and SG (6.7%)	8 to 28 weeks (mean: 12.5 weeks)	Liraglutide 1.8mg	The mean postoperative period was 5.6 years, Range: 2-13 years <50% of excess weight loss after >2 years of follow-up, or regained ≥15% of lowest weight post-surgery	All patients lost weight (range: 2 to 18 kg, mean: 7.5 kg, p<.001).
Rye (2018)^14	20 M/F BMI: ND Mean age: 49.6 ± 8.3 years	Retrospective cohort	RNY (35%), SG (35%), VBG (15%), and AGB (15%)	28 weeks	Liraglutide 3.0 mg	76.3 ± 72.9 months Weight regain (>10%), inadequate weight loss (<20% weight loss from surgery) and plateau	At 16 weeks median percentage loss was 7.1% (IQR 5.1-12.2%), and at 28 weeks 9.7% (IQR 7.8-13.9%) (P-value for change from baseline N.R.).
Schwartz (2016)^16	65 M/F BMI: 39.3 kg/m^2Mean age: 47.3 ± 0.8 years	Retrospective cohort	RNY (78%), and AGB (22%)	90 days	Phentermine or combination phentermine and topiramate	The median time from minimum weight post-surgery to initiate Ph cohort was 35.3 months and for PhT cohort was 36.3 months. Patients had to have a BMI of 27–29.9 kg/m2 with at least one comorbid condition, or a BMI >30 kg/m2 without co-morbidities.	All patients lost weight. Patients taking phentermine (6.3kg) lost more weight than those taking a combination of phentermine and topiramate (3.8kg, p =.025). Weight loss did not differ by type of surgery. (p = .345).
Srivastava (2018)^10	48 M/F BMI: 38.3 kg/m^2Age: NR	Retrospective cohort	RNY (52.0%), SG (29.2%) and AGB (18.8%)	NR	Metfromin, phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, zonsiamide, topiramate, and glucose-like 1 agonists	Mean time of 6.1 ± 4.6 years (range: 1-20 years) ND	Bariatric surgery patients taking no WL meds, 1 WL med, or ≥ 2 WL meds lost 2.2 kg, 2.7 kg, and 5.7 kg, respectively (change from baseline P-value NR, P-value for trend p =.05). Non-bariatric surgery patients who took 0 WL meds, 1 WL med, or ≥2 WL med lost 4.8 kg, 6.8 kg, 9.5 kg (change from baseline p-value NR, p-value for trend <.05). No significant difference in WL for those ≥ 2 meds based on bariatric surgery status (p =.08).
Stanford (2017)^9	319 M/F BMI RNY: 36.8 kg/m^2 SG: 37.5 kg/m^2Age range: 20-73 years	Retrospective cohort	RNY (80.9%) and SG (19.1%)	NR	Phentermine, topiramate, zonisamide, metformin, bupropion, orlistat, sibutramine, liraglutide, exenatide, pramlintide, naltrexone, lorcaserin, phentermine/topiramate, canagliflozin or bupropion/naltrexone	SG: 23.2 ± 15.3 months RNY: 59.3 ± 36.7months After weight regain (78.5%; n = 249) or at plateau (21.5%; n = 68). Amount ND.	Patients with RNY lost 9.0 kg and SG lost 4.5 kg. Patients with RNY were more likely to lose ≥10% and ≥ 15% of their weight than those with SG (p ≤ .03). Patients taking topiramate (9.2 kg) lost significantly more weight than those other weight loss medications (6.4 kg, P-value NR).
Stanford (2018)^7	35 M/F BMI RNY: 34.7 ± 5.8 5kg/m^2SG: 36.6 ± 3.6 5 kg/m^2≥60 years	Post-hoc retrospective cohort	RNY SG	NR	Phentermine, topiramate, zonisamide, metformin, bupropion, orlistat, sibutramine, liraglutide, exenatide, pramlintide, naltrexone, lorcaserin, phentermine/topiramate, canagliflozin, and bupropion/naltrexone	RNY: 38.5 ± 28.6 months SG: 26.2 ± 13.2 months Patients were more likely to be prescribed medications after weight regain (71.4%; n = 25) occurrence than at plateau (28.6%; n = 10)	Patients lost an average BMI of 2.74 ± 2.6 kg/m^2 on medications. . RNY patients lost a greater BMI than SG (3.37 ± 2.83 kg/m^2 vs. 1.38 ± 1.49 kg/m2, p =.0372). liraglutide more effective than the other medications. Coefficient observed for liraglutide β = −16.07 (p =.009, CI: -25.17-3.57).
Toth (2018)^8	37 M/F BMI: RNY: 38.9 ± 9.1 kg/m^2, SG: 37.3 ± 5.7 kg/m^2Range: 21-30 years	Post-hoc retrospective cohort	RNY (75.7%) and SG (25.7%)	NR	Topiramate, phentermine, and/or metformin	RNY: 62.6 ± 39.1 months SG: 20.1 ± 5.2 months ND	RNY had higher median percent weight loss (8.1%) than SG (3.3%; p = .0515). Median percent weight change on metformin was less than the rest of the cohort (-2.9% vs. 7.7%; p =.0241). No difference from the rest of the cohort for phentermine (p =.2018) or topiramate (p = .3187)
Zilberstein (2004)^4	16 M/F BMI: 45.3 kg/m^2Age range: 20-44 years	Prospective cohort	Swedish AGB	90 days	Topiramate or fluoxetine	ND Did not have acceptable weight loss (acceptable ND).	Patients lost 7.1 kg on average (p = .0139)^a
Zoss (2002)^17	38 M/F BMI: 41.0 kg/m^2Mean age: 50 ± 2.0 for AGB + DC and 47 ± 2.0 for AGB+Orlistat+DC	Matched prospective cohort	Swedish AGB	8 months	Orlistat	18 ± 6 months Stopped losing weight ≥3 months before study start	Patients taking orlistat lost significantly more weight (8 kg) than those not prescribed orlistat (2 kg, p<.02).

Abbreviations. M: Male; F: Female; AGB: Adjustable Gastric Banding; VBG: Vertical Banded Gastroplasty; RNY: Roux-En-Y Gastric Bypass; BPD: Biliopancreatic Diversion; ND: Not Reported; SG: Sleeve Gastrectomy; DC: Diet counseling; SEM: Standard error of the mean.

^aValue is calculated from postoperative weight minus post-topiramate weight using patient-level data.

Table 2. Global rating of quality assessment of articles.

Author	Rating
Gorgojo-Martinez^15	Strong
Guerdjikova^18	Moderate
Jester^11	Moderate
Nor Hanipah^13	Strong
Pajecki^12	Strong
Rye^14	Strong
Schwartz^16	Strong
Srivastava^10	Strong
Stanford^9	Strong
Stanford^7	Strong
Toth^8	Strong
Zilberstein^4	Weak
Zoss^17	Weak

Gorgojo-Martínez JJ, Feo-Ortega G, Serrano-Moreno C. Effectiveness and tolerability of liraglutide in patients with type 2 diabetes mellitus and obesity after bariatric surgery. Surg Obes Relat Dis. 2016;12(10):1856–1863.

 PubMed Web of Science ®Google Scholar

Guerdjikova AI, Kotwal R, McElroy SL. Response of recurrent binge eating and weight gain to topiramate in patients with binge eating disorder after bariatric surgery. Obes Surg. 2005;15(2):273–277.

 PubMed Web of Science ®Google Scholar

Nor Hanipah Z, Nasr EC, Bucak E, et al. Efficacy of adjuvant weight loss medication after bariatric surgery. Surg Obes Relat Dis. 2018;14(1):93–98.

 PubMed Web of Science ®Google Scholar

Jester L, Wittgrove AC, Clark GW. Adjunctive use of appetite suppressant medications for improved weight management in bariatric surgical patients. Obes Surg. 1996;6(5):412–415.

 PubMed Web of Science ®Google Scholar

Pajecki D, Halpern A, Cercato C, et al. Short-term use of liraglutide in the management of patients with weight regain after bariatric surgery. Rev Col Bras Cir. 2013;40(3):191–195.

 PubMedGoogle Scholar

Rye P, Modi R, Cawsey S, et al. Efficacy of High-Dose liraglutide as an adjunct for weight loss in patients with prior bariatric surgery. OBES SURG. 2018;28(11):3553–3558.

 PubMed Web of Science ®Google Scholar

Schwartz J, Suzo A, Wehr AM, et al. Pharmacotherapy in conjunction with a diet and exercise program for the treatment of weight recidivism or weight loss plateau post-bariatric surgery: a retrospective review. Obes Surg. 2016;26(2):452–458.,

 PubMed Web of Science ®Google Scholar

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.

 PubMed Web of Science ®Google Scholar

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.

 PubMed Web of Science ®Google Scholar

Stanford FC, Toth AT, Shukla AP, et al. Weight loss medications in older adults after bariatric surgery for weight regain or inadequate weight loss: a multicenter study. Bariatr Surg Pract P. 2018;13(4):171–178.

 PubMed Web of Science ®Google Scholar

Toth A, Gomez G, Shukla A, et al. Weight loss medications in young adults after bariatric surgery for weight regain or inadequate weight loss: a Multi-Center study. Children. 2018;5(9):116.

 Google Scholar

Zilberstein B, Pajecki D, De Brito ACG, et al. Topiramate after adjustable gastric banding in patients with binge eating and difficulty losing weight. Obes Surg. 2004;14(6):802–805.

 PubMed Web of Science ®Google Scholar

Zoss I, Piec G, Horber FF. Impact of orlistat therapy on weight reduction in morbidly obese patients after implantation of the Swedish adjustable gastric band. Obes Surg. 2002;12(1):113–117.

 PubMed Web of Science ®Google Scholar