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Surgery for Obesity and Related Diseases 14 (2018) 93–98

Original article
Efficacy of adjuvant weight loss medication after bariatric surgery
Zubaidah Nor Hanipah, M.D.a,b, Elie C. Nasr, B.A.a, Emre Bucak, M.D.a,
Philip R. Schauer, M.D.a, Ali Aminian, M.D.a, Stacy A. Brethauer, M.D.a, Derrick Cetin, D.O.a,*
a
Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio
b
Department of Surgery, Faculty of Medicine and Health Sciences, University Putra Malaysia, Selangor, Malaysia
Received March 27, 2017; accepted October 3, 2017

Abstract Background: Some patients do not achieve optimal weight loss or regain weight after bariatric
surgery. In this study, we aimed to determine the effectiveness of adjuvant weight loss medications
after surgery for this group of patients.
Setting: An academic medical center.
Methods: Weight changes of patients who received weight loss medications after bariatric surgery
from 2012 to 2015 at a single center were studied.
Results: Weight loss medications prescribed for 209 patients were phentermine (n ¼ 156, 74.6%),
phentermine/topiramate extended release (n ¼ 25, 12%), lorcaserin (n ¼ 18, 8.6%), and naltrexone
slow-release/bupropion slow-release (n ¼ 10, 4.8%). Of patients, 37% lost 45% of their total
weight 1 year after pharmacotherapy was prescribed. There were significant differences in weight
loss at 1 year in gastric banding versus sleeve gastrectomy patients (4.6% versus .3%, P ¼ .02) and
Roux-en-Y gastric bypass versus sleeve gastrectomy patients (2.8% versus .3%, P ¼ .01).There was
a significant positive correlation between body mass index at the start of adjuvant pharmacotherapy
and total weight loss at 1 year (P ¼ .025).
Conclusion: Adjuvant weight loss medications halted weight regain in patients who underwent
bariatric surgery. More than one third achieved 45% weight loss with the addition of weight loss
medication. The observed response was significantly better in gastric bypass and gastric banding
patients compared with sleeve gastrectomy patients. Furthermore, adjuvant pharmacotherapy was
more effective in patients with higher body mass index. Given the low risk of medications compared
with revisional surgery, it can be a reasonable option in the appropriate patients. Further studies are
necessary to determine the optimal medication and timing of adjuvant pharmacotherapy after
bariatric surgery. (Surg Obes Relat Dis 2018;14:93–98.) r 2018 American Society for Metabolic
and Bariatric Surgery. All rights reserved.

Keywords: Bariatric surgery; Weight loss; Medications; Adjuvant; Obesity; Weight; Phentermine

Obesity is a global health problem and has a strong cardiovascular diseases. In the United States, more than
association with metabolic disorders such as type 2 one third of the population has a body mass index (BMI)
diabetes, hypertension, hyperlipidemia, and other 430 kg/m2, and these numbers are increasing every year. If
these obesity trends continue, the total healthcare costs
This study was presented at the 33nd Annual Meeting of the American could reach $957 billion by 2030 [1].
Society for Metabolic and Bariatric Surgery at Obesity Week, New Bariatric surgery has evolved since the 1950s and is
Orleans, LA; October 31 to November 4, 2016.
*
Correspondence: Derrick Cetin, D.O., Bariatric and Metabolic Insti-
proven to be the most effective and have the best long-term
tute, Cleveland Clinic, 9500 Euclid Avenue, M61, Cleveland, OH 44195. success in the management of obesity. Furthermore, it also
E-mail: CETIND@ccf.org has been shown to improve most of the metabolic disorders
http://dx.doi.org/10.1016/j.soard.2017.10.002
1550-7289/r 2018 American Society for Metabolic and Bariatric Surgery. All rights reserved.
94 Z. N. Hanipah et al. / Surgery for Obesity and Related Diseases 14 (2018) 93–98

related to obesity, especially type 2 diabetes [2–6]. Accord- Definitions


ing to some estimates, a total of 196,000 bariatric surgeries
were performed in the United States in 2015 [7]. In the study, nadir weight was defined as the lowest
Despite the effectiveness of bariatric surgery, weight weight that the patient reached 12 to 18 months after
recidivism is seen in a proportion of patients after bariatric bariatric surgery. Weight regain was defined as o50%
procedures [8–10]. The causes of weight regain or recurrent excess weight loss or regain of at least 5% of nadir weight
disease is multifactorial; noncompliance to dietary recom- despite dietary counseling and behavioral and lifestyle
mendations, physiologic compensatory mechanisms, meta- changes.
bolic imbalances, behavioral changes like binge eating or
grazing, sedentary lifestyle or physical inactivity, and post- Dietary and exercise consultation
operative complications can all affect patient weight [11]. Patients received dietary consultations after providing
Additionally, like any chronic disease, a subset of patients is their dietary histories. Consultations emphasized the impor-
refractory to treatment as a result of genetic and environ- tance of getting 40% of carbohydrate, 30% of protein, and
mental influences. There are options available to address 30% of fat from the daily calorie intake. In our practice,
weight recidivism depending on the contributing factors, post–bariatric surgery patients are on approximately 500 to
including lifestyle modifications, pharmacotherapy, endo- 800 calories at 1 month, 800 to 1000 calories at 3 months,
scopic, and surgical revisional procedures. and should be on between 1000 and 1200 calories at 3 to 12
While revisional surgery can be performed to address the months. The calorie intake varies and is based on the height
anatomic causes of weight regain such as pouch and stoma of the patient and the patient’s specific activity level. All
dilation after Roux-en-Y gastric bypass (RYGB) [11], most patients were prescribed mineral and vitamin supplementa-
revisional bariatric procedures carry a higher morbidity tions as per the American Society and Metabolic and
compared with the primary procedures. Pharmacotherapy Bariatric Surgery guidelines [16]. Patients were encouraged
may play an alternative role in these patients who have an to participate in 150 to 300 minutes of exercise a week.
increased risk of undergoing revisional surgery or poor All bariatric surgical patients were followed up at 1, 3, 6,
compliance to lifestyle modification. The use of the appetite 9, 12, 18 months, and annually thereafter with a multi-
suppressant, phentermine has been widespread since 1959 disciplinary team including a dietician, psychologist, bari-
[12]. Despite more recent chronic weight loss medications, atric physician, and bariatric surgeon. Weight and excess
such as phentermine/topiramate, lorcaserin, naltrexone/ weight loss were monitored during the follow-up. The
bupropion, and liraglutide 3.0 mg, that are available, decision to prescribe weight loss medications was made
phentermine is still the least expensive and most commonly after a multidisciplinary team discussion.
prescribed weight loss medication in the United States
[12–15]. Therefore, pharmacotherapy tailored to the
patient’s needs post–bariatric surgery, acting as an adjunct Prescription of weight loss medication
to dietary education and behavioral changes, can potentially The patients who had poor weight loss or weight regain
halt weight regain. In this retrospective study, the aim was were prescribed weight loss medications to suppress appe-
to determine the effectiveness of adjuvant weight loss tite. The weight loss medications included phentermine,
medications after bariatric surgery for this group of patients. phentermine/topiramate extended-release, lorcaserin, and
naltrexone slow-release/bupropion slow-release (Table 1).
Methods The choice of the weight loss medications was individu-
alized, weighing the potential benefits with the risk of the
A retrospective chart review study was conducted after drugs. The choice of the weight loss medications is often
institutional research board approval. All patients who governed by the co-morbidities and the relative contra-
received weight loss medications after bariatric surgery indications present in each patient. All 4 weight loss
from 2012 to 2015 were identified at a single academic medications prescribed were used according to this criteria.
center. Patients who had weight regain or poor weight loss After prescription of weight loss medications, patients were
after bariatric surgery were included based on the following followed carefully to ensure they met 5% weight loss at
inclusion criteria: (1) patients 418 years of age; (2) patients 12 weeks. Those who did not lose weight or had side effects
who experienced o50% excess weight loss or regained at from the weight loss medication were asked to stop or
least 5% of their nadir weight despite dietary counseling switch the medications.
and behavioral and lifestyle changes; and (3) patients who
were placed on weight loss medication for a minimum of Data collection
3 months with a minimum follow-up period of 1 year.
A total of 443 patients were prescribed weight loss Data collected include baseline characteristics, co-
medications, but only 209 patients continued the medication morbidities, perioperative parameters, postoperative out-
use for at least 3 months. comes, type of weight loss medication, and weight and
Effectiveness of Adjuvant Weight Loss Medications After Surgery / Surgery for Obesity and Related Diseases 14 (2018) 93–98 95

Table 1 were on low-dosage liraglutide prescribed by the endocri-


Prescribed weight loss medications nologist for diabetes control (1.2–1.8 mg daily).
These patients were followed up at 3 (n ¼ 199, 95%) and
Weight loss Dosage
medication
12 months (n ¼ 159, 76%). Weight loss outcomes at 3 and
12 months after initiation of pharmacotherapy have been
Phentermine • 37.5 mg daily for 3 mo at a time detailed in Table 3 and Figs. 1 and 2. The overall TWLs at
Phentermine/ • 3.75 mg/23 mg daily for 14 d followed by
• 7.5 mg/46 mg daily maintenance dose
3 and 12 months were 3.2% and 2.2%, respectively. The
Topiramate ER TWL 45% after adjuvant pharmacotherapy at 1 year was
And
• This dose was increased to the intermediate dose observed in 37%. The TWL 410% at 1 year are seen in
of 11.25 mg/69 mg (if the patient did not lose 19%.
about 5% weight in 12 weeks) One year after using the adjuvant pharmacotherapy, we
And observed a significant difference in weight loss at 1 year in
• Titration to the full dosage of 15 mg/92 mg
(if patients did not achieve 5% weight loss with LAGB versus SG (4.6% versus .3%, P = .02) and RYGB
the previous dose) versus SG (2.8% versus .3%, P = .01) (Table 3). Compared
Lorcaserin • 10 mg twice daily with SG, significantly more patients in the LAGB and
Naltrexone SR/ • 8 mg/90 mg daily titrated to a full dose of RYGB groups achieved TWL 45% and 410% at 1 year
Bupropion SR 32 mg/360 mg by increasing weekly until on
the full dose after 4 wk
after pharmacotherapy (Fig. 2).
There was a significant positive correlation between BMI
Topiramate ER ¼ topiramate extended-release; Naltrexone SR/Bupro-
at the start of adjuvant pharmacotherapy and %TWL at
pion SR ¼ naltrexone sustained-release/bupropion sustained-release.
1 year (P ¼ .025). The %TWL for patients with BMI ≥36
versus those with BMI o36 were 3.5 ± 7.9% and .9 ±
BMI pre– and post–bariatric surgery at nadir, prepharma-
7.0%, respectively (P ¼ .027). There was no significant
cotherapy, and at 3 months and 1 year after prescription of
correlation between presurgery weight and presurgery BMI
weight loss medication. Percent total weight loss (TWL)
with %TWL 1 year after initiation of pharmacotherapy.
was calculated as (operative weight − follow-up weight /
operative weight) × 100. The outcome of the weight and
BMI after weight loss medications was analyzed as a whole,
not according to each type of weight loss medication Discussion
prescribed.
Bariatric surgery has been shown to be a safe, effective,
and durable treatment for obesity. However, 10% to 20% of
Statistical analysis patients regain weight or fail to sustain weight loss [9].
Data were summarized as the mean ± standard deviation Weight regain or failure to lose weight occurs with almost
or median (interquartile range) for continuous variables and all bariatric procedures. Sugerman et al. [10] reported that
as counts and percentages for categoric variables. Differ- excess weight loss decreases after RYGB over time from
ences between groups were compared with student t test 66% (at 1–2 yr) to 50% (at 10 yr). Sjostrom et al. [8]
and χ2 test. Correlations were analyzed with Pearson’s test. showed that there was weight regain of 7% from the second
Inference was based on a 2-sided 5% level.
Table 2
The demographic data at the time of bariatric surgery (N ¼ 209)
Results Parameters Number (%)
After bariatric surgery, 209 patients received weight loss Age, yr 50.9 (±10.5)
medications from 2012 until 2015 in our center with a Sex, female/male 195 (93.3)/14 (6.7)
minimum follow-up of 3 months. Bariatric procedures Hypertension 95 (45.5)
Dyslipidemia 57 (27.3)
included RYGB (n ¼ 126), sleeve gastrectomy (SG,
Type 2 diabetes 45 (21.6)
n ¼ 52), laparoscopic adjustable gastric banding (LAGB, Coronary artery disease 1 (.5)
n ¼ 21), gastric plication (n ¼ 4), and revisional bariatric Chronic obstructive pulmonary disease 2 (1.0)
surgery (n ¼ 6). Patient characteristics are summarized in Lower extremity joint pain 31 (14.8)
Table 2. Back pain 28 (13.4)
Depression 47 (22.5)
Median time interval between surgery and starting of
Anxiety 12 (5.7)
adjuvant pharmacotherapy was 38 months (interquartile Roux-en-Y gastric bypass 126 (60.3)
range, 24–63). The adjuvant medications used were phen- Sleeve gastrectomy 52 (24.9)
termine (n ¼ 156, 74.6%), phentermine/topiramate Laparoscopic adjustable gastric band 21 (10.0)
extended release (n ¼ 25, 12%), lorcaserin (n ¼ 18, Gastric plication 4 (1.9)
Revisional surgery 6 (2.9)
8.6%), and naltrexone slow-release/bupropion slow-release
(n ¼ 10, 4.8%). Out of 45 diabetic patients in our cohort, 12 Data presented as mean (±standard deviation) or number (%).
96 Z. N. Hanipah et al. / Surgery for Obesity and Related Diseases 14 (2018) 93–98

Table 3
Summary of weight and BMI changes after adjuvant pharmacotherapy
Mean weight changes, kg Mean BMI changes, kg/m2 Percent total weight loss (TWL%)

3 mo 12 mo 3 mo 12 mo 3 mo 12 mo

Laparoscopic adjustable gastric band −4.5 −4.6 −1.7 −1.7 4.6 4.6*
Roux-en-Y gastric bypass −3.2 −3.2 −1.2 −1.2 3.2 2.8†
Sleeve gastrectomy −2.4 −.3 −.9 .1 2.5 .3
Total cohort −3.2 −2.4 −1.2 −.9 3.2 2.2

BMI ¼ body mass index.


*
P value ¼ .01 versus sleeve gastrectomy.

P value ¼ .02 versus sleeve gastrectomy.

year to the 10th year after RYGB, AGB, and vertical band good safety profile [21,22]. Short-term use of phentermine
gastroplasty. and the combination of phentermine-topiramate until 1 year
Weight recidivism after bariatric surgery can be multi- have been shown to result in 5% to 10% excess weight loss
factorial and results from noncompliance to dietary guide-
lines and calorie intake, poor eating behaviors, physical
inactivity, and metabolic and anatomic complications.
Studies have shown that eating disorders, such as binge
eating or grazing, result in weight regain after bariatric
surgery [17,18]. Kofman et al. [18] conducted a survey on
maladaptive eating patterns and weight outcome after
gastric bypass. It was reported that 87% of patients regained
weight after gastric bypass at a mean follow-up of 4 years.
Binge eating, grazing, and a loss of control when eating
showed significant correlation with greater weight regain
after surgery. Magro et al. [19] showed that 78% had weight
regain at 18 months post-RYGB. Of patients, 60% avoided
nutritional follow-up and 80% never underwent psycholog-
ical follow-up. Yimcharoen et al. [20] studied the possible
anatomic causes of weight recidivism after gastric bypass.
Dilation of stoma, enlarged pouch, or both were seen in
59%, 29%, and 12% of patients, respectively.
Weight recidivism post–bariatric surgery can be an
important issue, both for patients and bariatric surgery
teams. Permanent lifestyle modification including changes
in eating habits and calorie intake, increasing physical
activity, and overcoming stressful events leading to binge
eating can be difficult. Failure to lose weight or early weight
loss plateau can cause additional frustration and anxiety for
patients, resulting in an increase in appetite and binge eating
behavior. Therefore, multidisciplinary team approaches and
proper strategies to manage weight regain or failure to lose
adequate weight in these patients are recommended.
The use of weight loss medication as an adjunct to
treatment of weight regain or inability to lose adequate
weight after bariatric surgery would be considered, espe-
cially in patients who are at high risk for revisional surgery.
Weight loss medications have been available since 1959
and were used in patients who were not suitable candidates
for bariatric surgery. Phentermine has been the most
commonly prescribed weight loss medication in the United
States, despite other newer weight loss medications that are Fig. 1. (A) Mean weight. (B) Mean body mass index (BMI). LAGB ¼
available [12–15]. Even though some of the old weight loss laparoscopic adjustable gastric band; RYGB ¼ Roux-en-Y gastric bypass;
medications had cardiac side effects, phentermine has a SG ¼ sleeve gastrectomy.
Effectiveness of Adjuvant Weight Loss Medications After Surgery / Surgery for Obesity and Related Diseases 14 (2018) 93–98 97

Fig. 2. (A) Total weight loss (TWL) 45% at 3 months after adjuvant pharmacotherapy. (B) TWL 45% at 12 months after adjuvant pharmacotherapy.
(C) TWL 410% at 3 months after adjuvant pharmacotherapy. (D) TWL 410% at 12 months after adjuvant pharmacotherapy. LAGB ¼ laparoscopic
adjustable gastric band; RYGB ¼ Roux-en-Y gastric bypass; SG ¼ sleeve gastrectomy.

[23–25]. Schwartz et al. [12] reported 12.8% excess weight data showed a positive correlation between TWL and
loss after phentermine use (n ¼ 24) and 12.9% excess BMI at time of pharmacotherapy, BMI before surgery
weight loss after phentermine-topiramate use (n ¼ 6) at 90 did not correlate with weight loss outcomes of adjuvant
days in patients after RYGB or AGB. In our cohort, pharmacotherapy.
phentermine and phentermine-topiramate extended-release As a retrospective observational study, compliance with
were the 2 most commonly used weight loss medications, weight loss medications, dietary regimen, and exercise were
comprising a combined total of 86.8% of prescriptions. difficult to assess in our cohort. Furthermore, we were not
In our series, 37% of patients achieved additional able to differentiate the effects of lifestyle modification from
TWL 45%, and 19% of patients achieved an additional pharmacotherapy. Lack of a control group and missing data
TWL 410% at 1 year. Patients with history of AGB and limited our study. Despite the 3-month follow-up being
RYGB showed a higher percentage of TWL 45% at 1 year 95%, the 1-year follow-up was only 76%. This is due to
compared with SG. Patients with AGB and RYGB showed various factors, including financial constraints, intolerance
significantly higher TWL at 1 year compared with SG. In of adjuvant pharmacotherapy, and patients lost to follow-
our cohort, the BMI at the start of adjuvant pharmacother- up. Furthermore, we were not able to analyze the efficacy of
apy and TWL at 1 year showed a significant positive any specific drugs or the different combinations of the
correlation. Patients with BMI ≥36 kg/m2 had greater TWL weight loss medications on weight loss outcome. The
after taking adjuvant pharmacotherapy. strength of our study is that this is one of the largest series
In a recently published multicenter study, Stanford et al. from an academic center comparing the outcome of
[26] showed that 56% of patients had TWL 45% at 1 year adjuvant weight loss medications in patients who underwent
of using weight loss medications after bariatric surgery. The 1 of the 3 common bariatric procedures.
mean added weight loss was −7.6% (17.8 lbs) of total
postsurgical weight. Similar to our observation, RYGB
Conclusion
patients had better weight loss outcomes with weight loss
medications compared with SG patients. Patients with Obesity is a chronic disease, and weight recidivism is an
higher BMI before bariatric surgery showed better weight issue to be addressed after bariatric surgery, with a multi-
loss after use of weight loss medications. While our disciplinary team approach. Our experience using adjuvant
98 Z. N. Hanipah et al. / Surgery for Obesity and Related Diseases 14 (2018) 93–98

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