Chapter 25 - Preventing Weight Regain after Weight Loss Page 1 of 11

25 Preventing Weight Regain after Weight Loss

Stephen D. Anton and Michael G. Perri
DOI: 10.1201/9781003432807-25

25.1 WEIGHT REGAIN FOLLOWING LIFESTYLE TREATMENT FOR OBESITY

Most adults who lose weight will regain more than half of their lost weight within 3 years of completing treatment. Indeed, the
failure to maintain weight reduction represents the single greatest barrier to the successful management of obesity. In this
chapter, we describe various biological, bio-behavioral, environmental, and psychological contributors to the regaining of lost
weight, and we review findings from recent randomized clinical trials testing a variety of interventions designed to improve long-
term weight-loss outcomes.
Comprehensive lifestyle interventions are commonly viewed as the first line of treatment for obesity [1, 2, 3]. These
interventions utilize the principles of behavioral psychology to facilitate changes in diet and physical activity that, over the
course of 4–6 months, reliably produce body weight reductions of 5–10% [1, 2, 3, 4]. Weight losses of this magnitude can
prevent the onset of type 2 diabetes and reduce risk factors for heart disease and obesity-related medical conditions [1, 5, 6].
Although effective in producing short-term weight loss, lifestyle interventions have not been as successful in sustaining weight
reductions [7, 8]. If weight losses are not maintained, the health benefits associated with losing weight may not be sustained [9].
An examination of the weight changes experienced by adults who complete lifestyle treatment without follow-up care
commonly shows a “checkmark” pattern. Treatment-induced weight loss is commonly followed by a regaining of 30–50% of the
initial reduction during the first year following treatment [7]. The rate of regain generally slows during the subsequent 2 years
before reaching a plateau, reflecting maintenance of 30–40% of the initial loss [10, 11]. This pattern is illustrated in longitudinal
data from those participants in the Weight Loss Maintenance Trial [10] who received lifestyle treatment and were subsequently
assigned to “self-directed care” (see Figure 25.1). Over the past four decades, numerous studies have reported similar findings
documenting that the real challenge in the treatment of obesity resides not in getting participants to lose weight but in helping
them keep it off [7, 12].

FIGURE 25.1 A typical pattern of weight change observed in lifestyle treatment without follow-up
intervention. (Based on data from the Weight Loss Maintenance Trial [10]).

25.2 UNDERSTANDING THE MAINTENANCE PROBLEM

What makes the maintenance of lost weight so difficult to achieve? The answer lies in a complex interaction of biological, bio-
behavioral, environmental, and psychological variables that promote a positive energy balance following weight loss, thereby
resulting in a regaining of lost weight [13, 14, 15, 16, 17, 18, 19] (see Figure 25.2).

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FIGURE 25.2 Factors contributing to weight regain following weight loss.

25.2.1 Biological Contributors

Following a period of diet-induced weight loss, compensatory changes in the neural pathways that regulate appetite may promote
increased energy (calorie) consumption. Hormonal signals from adipose tissue (e.g., leptin) and the gastrointestinal tract (e.g.,
ghrelin, glucagon-like peptide-1 [GLP-1], peptide YY) produce increases in hunger and decreases in satiety [19]. Moreover, after
an interval of dieting, the metabolic rate appears to be reduced due to the persistence of adaptive thermogenesis [20]. People who
have lost weight typically require fewer calories to sustain their lower body weights than individuals of the same weight who
have not experienced weight loss. Thus, the compensatory changes in appetite and metabolism that follow weight loss suggest
that the increased drive to eat and weight regain that commonly follow obesity treatment reflect to a significant degree the impact
of biological factors rather than a simple failure of willpower [13].

25.2.2 Bio-behavioral Contributors

Particular patterns of food consumption may influence the hormonal and metabolic processes that promote the regain of lost
weight [21, 22]. Intake of a large number of calories during a given meal or episode of binge eating can increase post-prandial
levels of blood glucose and triglycerides, thereby triggering the release of large amounts of insulin and other counter-regulatory
hormones [23, 24]. The increased insulin response may facilitate the storage of fat [25]. Moreover, it may also lead to
hypoglycemia, a concomitant increase in hunger, and further eating, thus initiating a cycle that promotes the regaining of lost
weight [26].

25.2.3 Environmental Contributors

The external environment provides an additional challenge to the individual who has achieved weight loss via behavioral changes
in eating and exercise [16, 27]. Bombarded with a barrage of cues to consume low-cost, highly-palatable, energy-dense foods,
most individuals succumb to deviations from the low-calorie regimens recommended for sustaining lost weight [27]. Often,
occasional dietary deviations initiate a return to previous patterns of eating that entail sustained increases in energy consumption
[28]. Unfortunately, these deviations often occur when compensatory mechanisms are calibrated to facilitate weight gain [14].
Furthermore, the obesogenic environment also exerts a significant influence on energy expenditure [29, 30]. Numerous labor-
saving devices have decreased the need for physical activity. In addition, the social environment places an enormous premium on
time, and a lack of time due to competing demands represents a key factor that leads many individuals to curtail their exercise
routines [31, 32]. Thus, the person who has completed weight-loss treatment faces strong and pervasive environmental influences
that encourage increased energy consumption and decreased expenditure precisely at a time when compensatory hormonal and
metabolic processes are primed to produce a regaining of lost weight [14].

25.2.4 Psychological Contributors

For most individuals who have completed weight-loss treatment, lapses in diet and exercise routines are common experiences
that are frequently accompanied by increases in body weight. These setbacks often trigger dysfunctional thoughts (e.g., “I am a
failure”) and negative emotions (e.g., anxiety or depressed mood) that may result in a further reduction of healthy weight-
management behaviors, consequently leading to additional weight gain [17, 18]. This regain occurs when there are fewer
reinforcements to maintain adherence to lifestyle changes initiated during treatment such as the advice of an interventionist or the
support of other participants in group treatment. Furthermore, during the post-treatment period, the effort required to maintain
lost weight is very similar to the effort required to lose weight, yet the reward of additional weight loss rarely occurs. This

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unfavorable cost-benefit ratio, coupled with negative thoughts and feelings and a lack of support from others, may lead to an
abandonment of the entire weight-control effort [17, 33, 34].

25.3 INTERVENTIONS TO IMPROVE THE MAINTENANCE OF WEIGHT LOSS

Over the past four decades, numerous studies have been conducted that address the maintenance problem either by enhancing
initial treatment to better equip participants to sustain their weight losses or by offering an additional phase of intervention to
provide participants with assistance or training following initial treatment. These interventions have typically targeted one or
more of the contributors described above that promote weight regain.
The Guidelines for Managing Overweight and Obesity in Adults (Guidelines), published jointly by the American Heart
Association (AHA), the American College of Cardiology (ACC), and The Obesity Society (TOS) [1], summarize evidence-based
methods associated with improved maintenance of weight loss and recommend that obesity interventions include the following
elements:

• Reduced calorie diet—with macronutrient composition based on the participant’s preference.

• Exercise—200–300 min/wk of aerobic activity, such as brisk walking.
• Extended care—monthly or more frequent face-to-face or telephone sessions for > 1 year with a trained interventionist focused on the use of
cognitive-behavioral strategies.
• Self-monitoring—ongoing monitoring of weight and occasional to frequent monitoring of food intake and physical activity, with feedback and
advice provided by a trained interventionist.

In the following sections, we provide brief descriptions of selected randomized clinical trials (RCTs, published between January
1, 2016, and July 1, 2021) that examined the effects of interventions designed to enhance long-term weight outcomes. We focus
on trials that included: (a) a lifestyle core to produce initial changes in diet and physical activity, (b) randomized assignment to
an experimental intervention/maintenance program or an appropriate control/comparison condition, (c) an initial weight loss
>5% of baseline weight, and (d) a follow-up conducted >12 months from baseline (see Table 25.1).

TABLE 25.1 Randomized Trials of Interventions Designed to Enhance Maintenance of Lost Weight
Intervention type
Diet and exercise interventions
Initial Randomized Follow-up at end of
Study Sample Additional follow-up
treatment conditions maintenance program
Mean Mean Mean Mean
N BMI Months change Months
Retention change
Months
Retention change
Author from from from
(total) (kg/m2) from (%) from (%) from
baseline baseline baseline
atbaseline baseline baseline baseline
Carter et al. 137 35.0 3 –6.3 kg Intermittent energy 12 70% –7.1 kg 24 61% –4.4 kg
[36] restriction (overall)
37.0 3 –5.2kg Continuous energy 12 –4.6 kg 24 –3.6 kg
restriction
Christensen 153 34.0 16 –10.3 kg Intermittent use of 52 70% –9.6 kg None NA NA
et al. [37] low-calorie diet
(810 kcal/day) for 3
periods per year,
each lasting 5
weeks
32.6 –10.6 kg Availability of 52 71% –8.9 kg None NA NA
formula diet
products as
substitutes for 1-2
meals per day
Kaikkonen 120 35.7 3 –9.1ab kg Behavioral treatment 9 75% –8.7a kg 24 70% –5.5ab kg
et al. [41] (overall)
36.1 3 a
–9.2 kg Behavioral treatment 9 a
–10.0 kg 24 77% –8.5a kg
+ exercise (0–3 mo)
36.5 3 –6.1b kg Behavioral treatment 9 –6.9a kg 24 73% –4.4b kg
+ exercise (6–9 mo)
36.9 3 –0.8c kg Control 9 0.0b kg 24 63% 0.9c kg
Madjd et al. 71 33.7 (overall) 6 –8.5 kg Hypocaloric diet + 18 77% –10.2a kg None NA NA
[39] water
6 –7.6 kg Hypocaloric diet + 18 81% –7.8b kg None NA NA
diet beverage
Raben et al. 2223 35.7 2 –11.0* kg High protein/low 34 52% (overall) range across None NA NA
[43] (overall) glycemic index diet four groups
+ high-intensity = –4.6 to
exercise –4.9 kg

Abbreviations: BMI = body mass index; NA = not applicable.

Note: Differing superscripts adjacent to means indicate significant (p <0.05) between-group differences.
* Included the use of a low-calorie diet or meal replacements during the initial phase of treatment.
#
Following a 30-month weight-loss maintenance intervention, participants were randomly assigned to either a “personal contact—active” condition
with continued contact or to a “personal contact—control condition” without additional contact.

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Intervention type
Diet and exercise interventions
Initial Randomized Follow-up at end of
Study Sample Additional follow-up
treatment conditions maintenance program
Mean Mean Mean Mean
N BMI Months change Months
Retention change
Months
Retention change
Author from from from
(total) (kg/m2) from (%) from (%) from
baseline baseline baseline
atbaseline baseline baseline baseline
35.1 2 High protein/low 34 None NA NA
glycemic index diet 34
+ moderate
intensity exercise
35.0 2 Moderate None NA NA
protein/moderate
glycemic index diet
+ high-intensity
exercise
35.7 2 Moderate 34 None NA NA
protein/moderate
glycemic index diet
+ moderate
intensity exercise
Washburn et 235 31.8 3 -9.7 kg 150 min/wk of 15 74% (overall) –8.6 kg None NA NA
al. [42] moderate-to-
vigorous intensity
exercise
32.1 3 –9.4 kg 225 min/wk of 15 –6.2 kg None NA NA
moderate-to-
vigorous intensity
exercise
31.7 3 –9.3 kg 300 min/wk of 15 –6.5 kg None NA NA
moderate-to-
vigorous intensity
exercise
Extended care interventions
Befort et al. 172 33.5 6 –12.2* kg Group phone 18 87% –8.9a kg None NA NA
[48] counseling
34.5 6 –13.2* kg Newsletter 18 92% –8.3b kg None NA NA
comparison
Coughlin et 745 33.6 6 –7.9 kg Personal 36 94% ~–4.2a kg 66 83% ~ –2.9a kg
al. [51] contact—active
34.1 –7.9 kg Personal 36 94% ~–4.2a kg 66 84% ~ –3.6a kg
contact—control#
34.1 6 –8.2 kg Self-directed care 36 93% ~ –2.9b kg 66 84% ~ –1.6b kg
Dutton et al. 108 34.93 4 –7.5 kg Clustered campaign 16 87% –7.3a kg None NA NA
[47] maintenance
program
35.26 4 –7.6 kg Self-directed care 16 89% –5.4b kg None NA NA

Ilowiecka et 36 35.12 12 –4.7 kg Support group (diet + 30 90% –3.8a None NA NA

al. [45] exercise counseling
+ motivation
interviewing +
cognitive
behavioral therapy)
34.88 12 Control group (no 30 +2.5b None NA NA
additional care)
Mai et al. 143 37.4 (overall) 3 –4.7 kg/m2 Weight maintenance 15 89% ~ –4.6a kg/m2 21 83% ~ –3.4 kg/m2
[46] (overall) program

3 Control (no further 15 82% ~ –3.7b kg/m2 21 72% ~ –3.1

treatment) kg/m2
Perri et al. 445 36.3 4 -8.4 kg Individual phone 16 86% –8.5a kg 22 84% –6.1a kg
[49] 37.0 counseling
4 -8.7 kg Group phone 16 86% –7.5ab kg 22 85% –5.9ab kg
counseling
36.1 4 -7.8 kg Education control 16 90% –5.4b kg 22 91% –3.7b kg
Vitolins et 82 32.5 24 –5.0 kg Group maintenance 72 85% a
–5.7 kg None NA NA
al. [50] program
33.8 24 –5.4 kg Self-directed 72 88% +0.3b kg None NA NA
maintenance
program
Psychological/mindfulness/acceptance interventions
Butryn et al. 320 35.8 6 –9.9 kg Acceptance-based 18 71% –9.1 kg None NA NA
[57] behavioral therapy
+ physical activity
emphasis

Abbreviations: BMI = body mass index; NA = not applicable.

Note: Differing superscripts adjacent to means indicate significant (p <0.05) between-group differences.
* Included the use of a low-calorie diet or meal replacements during the initial phase of treatment.
#
Following a 30-month weight-loss maintenance intervention, participants were randomly assigned to either a “personal contact—active” condition
with continued contact or to a “personal contact—control condition” without additional contact.

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Intervention type
Diet and exercise interventions
Initial Randomized Follow-up at end of
Study Sample Additional follow-up
treatment conditions maintenance program
Mean Mean Mean Mean
N BMI Months change Months
Retention change
Months
Retention change
Author from from from
(total) (kg/m2) from (%) from (%) from
baseline baseline baseline
atbaseline baseline baseline baseline
34.5 6 –10.2 kg Behavioral therapy + 18 75% –12.4 kg None NA NA
physical activity
emphasis
35.1 6 –10.5 kg Standard behavioral 18 64% –10.2 kg None NA NA
therapy
Daubenmier 194 35.4 6 –5.2 kg Lifestyle (diet + 18 76% –5.0 kg None NA NA
et al. [54] exercise) treatment (overall)
+ mindfulness
35.6 6 –4.0 kg Lifestyle (diet + –3.2 kg None NA NA
exercise) treatment
only
Knauper et 172 28-45 (range) 12 –10.6 kg Enhanced (habit 24 57% –4.9 kg None NA NA
al. [52, formation) Diabetes
53] Prevention Program
intervention
12 –6.0 kg Standard Diabetes 24 69% –2.5 kg None NA NA
Prevention Program
intervention
Lillis et al. 162 37.5 12 –8.9 kg Acceptance-based 24 78% –4.3 kg None NA NA
[55] behavioral
intervention
37.7 –9.7 kg Standard behavioral 79% –2.6 kg None NA NA
treatment
Lillis et al. 102 34.5 3 –10.3a kg Acceptance 6 94% –9.8a kg 24 79% –7.0a kg
[56] commitment
therapy workshop +
3 monthly phone
calls + weekly
emails during
months 4 to 6
34.2 3 –10.0a kg Self-regulation 94% –9.1a kg 24 79% –4.0ab kg
workshop + 3
monthly phone calls
+ weekly emails
during months 4 to
6
34.4 3 –7.1b kg Weekly emails during 71% –6.2b kg 24 59% –1.1b kg
months 4 to 6
(control group)
Technology-enhanced interventions
Conroy et 194 30.9 12 (prior to -9.0 kg Electronic-Health 12 Not reported –8.4 kg 24 83% –6.9a kg
al. [61] start of (verified Record-based
trial) during weight-
prior year) management tools
and tracking +
personalized health
coaching
29.8 12 (prior to –10.2 kg Electronic Health 12 Not reported –8.3 kg 24 81% –5.3b kg
start of (verified Record-based
trial) during weight-
prior yr) management tools
and tracking only
Hagerman 301 28–45 (range) 6 6.1 kg Web-based 18 77% 5.0 kg 30 73% 3.8 kg
et al. [60] intervention +
professional
counseling via
email (months 6
–18)
6 5.1 kg Web-based 18 72% 4.9 kg 30 67% 4.1 kg
intervention plus
peer-led discussion
board (months 6
–18)
6 5.6 kg Web-based 18 81% 4.7 kg 30 76% 4.2 kg
intervention only
Jakicic et al. 471 31.5 6 –8.6 kg Technology-enhanced 24 76% –3.5b kg None NA NA
[64] behavioral
treatment
30.9 6 –8.0 kg Standard behavioral 24 73% –5.9a kg None NA NA
treatment

Abbreviations: BMI = body mass index; NA = not applicable.

Note: Differing superscripts adjacent to means indicate significant (p <0.05) between-group differences.
* Included the use of a low-calorie diet or meal replacements during the initial phase of treatment.
#
Following a 30-month weight-loss maintenance intervention, participants were randomly assigned to either a “personal contact—active” condition
with continued contact or to a “personal contact—control condition” without additional contact.

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Intervention type
Diet and exercise interventions
Initial Randomized Follow-up at end of
Study Sample Additional follow-up
treatment conditions maintenance program
Mean Mean Mean Mean
N BMI Months change Months
Retention change
Months
Retention change
Author from from from
(total) (kg/m2) from (%) from (%) from
baseline baseline baseline
atbaseline baseline baseline baseline
Sniehotta et 288 30.9 <12 –12.6 kg Technology-mediated, 12 91% –10.8 kg None NA NA
al. [62] low-intensity
maintenance
program (e.g.,
wirelessly
connected scales +
text messages)
30.8 <12 –14.4 kg Lifestyle advice via 12 92% –12.6 kg None NA NA
newsletter
Young et al. 92 33.0 (overall) 3 –7.3 kg Gender-tailored 9 83% (overall) –7.6a kg 39 71% (overall) –4.3 kg
[63] maintenance
program delivered
via text messages
and emails with
videos
3 –7.4 kg Control (no resources) 9 –5.8b kg 39 –3.8kg

Conroy et 194 30.9 12 (prior to –9.0 kg Electronic-Health 12 Not reported –8.4 kg 24 83% –6.9a kg
al. [61] start of (verified Record-based
trial) during weight-
prior year) management tools
and tracking +
personalized health
coaching
29.8 12 (prior to –10.2 kg Electronic Health 12 Not reported –8.3 kg 24 81% –5.3b kg
start of (verified Record-based
trial) during weight-
prior yr) management tools
and tracking only
Pharmacological interventions
Lundgren et 195 37.0 (overall) 2* –13.1 kg Liraglutide + 14 92% ~ –16.5a kg None NA NA
al. [68] (overall) moderate-to-
vigorous intensity
exercise
2* Liraglutide + usual 14 84% ~ –13.8ab kg None NA NA
physical activity
2* Placebo + moderate- 14 83% ~ –11.1b kg None NA NA
to-vigorous
intensity exercise
2* Placebo + usual 14 82% ~ –7.0c kg None NA NA
physical activity
Manning et 221 37.5 4 –7.1 kg Cabergoline 28 92% –2.4 kg None NA NA
al. [65]
37.3 4 –7.3 kg Placebo 28 88% –2.5 kg None NA NA
Rubino et 803 34.5 5 –11.1 kg Semaglutide (68 16 99% –18.2a kg None NA NA
al. [66] weeks) + lifestyle
counseling (16
monthly sessions)
34.1 5 –11.1 kg Semaglutide (20 16 97% –5.0b kg None NA NA
weeks) followed by
placebo (48 weeks)
+ lifestyle
counseling (16
monthly sessions)
Wadden et 611 38.1 16* –17.1a kg Semaglutide + NA NA NA None NA NA
al. [67] intensive lifestyle
counseling (30
sessions)
37.8 16* –5.9b kg Placebo + intensive NA NA NA None NA NA
lifestyle counseling
(30 sessions)

Abbreviations: BMI = body mass index; NA = not applicable.

Note: Differing superscripts adjacent to means indicate significant (p <0.05) between-group differences.
* Included the use of a low-calorie diet or meal replacements during the initial phase of treatment.
#
Following a 30-month weight-loss maintenance intervention, participants were randomly assigned to either a “personal contact—active” condition
with continued contact or to a “personal contact—control condition” without additional contact.

25.3.1 Diet and Exercise Interventions

The use of low-calorie, portion-controlled meals during the initial phase of treatment appears to increase both initial and long-
term weight loss [35]. In recent years, intermittent fasting has garnered significant attention as a strategy that might also improve
weight-loss outcomes. Carter and colleagues [36] assigned participants to either an intermittent fasting regimen (<600 kcal on

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two non-consecutive days/week) or to a continuous restriction diet (1200–1500 kcal/day on all days). Over the course of 24
months, both approaches produced similar changes in body weight.
Christensen and colleagues [37] examined the effects of intermittent low-calorie dieting in older adults with knee
osteoarthritis. Participants who previously achieved a mean weight loss of 10.5 kg were randomized to either an “intermittent”
diet (810 kcal/day), consisting of three, 5-week weight-loss intervals per year, or to a “regular” diet group with daily use of 1–2
meal replacements. Over the course of 3 years, weight regains in both conditions were relatively small, and the between-group
difference was not significant.
A topic of popular debate centers on the assertion that artificially sweetened beverages increase hunger and contribute to
weight gain [38]. If so, a reduction in diet drink consumption might assist in weight management. Madjd and colleagues [39]
randomly assigned women who were regular consumers of diet drinks either to continue their consumption of diet beverages or
to substitute water for diet drinks. During a 12-month maintenance period, the group that substituted water achieved a small but
significantly greater additional weight reduction than the diet beverage group.
Few trials have demonstrated improved long-term weight changes based on randomized assignments to different exercise
prescriptions [40]. Kaikkonen and colleagues [41] examined whether the addition or timing of 3 months of a supervised circuit
(resistance) training might improve weight-loss outcomes. Participants were assigned randomly to behavioral treatment (a)
without exercise, (b) with supervised circuit training during months 0–3, (c) with supervised circuit training during months 6–9,
or to (d) a no-treatment control group. All three active treatments (groups a, b, and c) produced greater weight changes than the
control group. The introduction of exercise during months 0–3 resulted in better long-term weight changes than the exercise
introduced during months 6–9. However, the inclusion of exercise failed to improve short- or long-term weight outcomes versus
behavioral treatment without exercise.
Washburn and colleagues [42] tested the effects of different levels of moderate-to-vigorous intensity exercise to reduce weight
regain following an initial three-month, weight-loss intervention. Participants who achieved a clinically meaningful weight loss
(>5% of baseline weight) were randomly assigned to one of three 12-month conditions that included behavioral treatments plus
150, 225, or 300 min/wk of exercise. Higher volumes of exercise failed to produce better weight loss maintenance.
In a multi-center trial that employed a two-by-two (diet by exercise) design, Raben and colleagues [43] randomized adults
with prediabetes to one of two diet conditions (high protein/low glycemic index versus moderate protein/moderate glycemic
index) crossed with two exercise conditions (high versus moderate intensity). Over the course of 3 years, no significant effects on
body weight were observed for diet or exercise or the interaction of diet and exercise.

25.3.2 Extended Care Interventions

Providing additional intervention and behavioral support during the posttreatment period typically improves the maintenance of
lost weight [1, 7, 44]. In recent years, several trials have examined different modalities for the delivery of extended care.
Iłowiecka and colleagues [45] randomized participants who completed a lifestyle intervention to either no additional care or a
support program that included monthly in-person individual and group sessions with a dietitian or psychologist and incorporated
an array of cognitive-behavioral strategies plus nutrition education and physical activity assessments. At a 30-month follow-up,
the support program participants maintained 81% of their initial losses, whereas the control participants regained their initial
losses plus additional weight. Mai and colleagues [46] examined the effects of a face-to-face extended care program, involving
dietary, exercise, and behavioral components, versus a control group that received maintenance advice provided via leaflets. At a
12-month follow-up, participants in the extended-care program sustained a greater proportion of initial weight losses than those
in the control group (98% versus 79%, respectively); however, the between-group difference was not significant at an 18-month
follow-up.
Dutton et al. [47] compared the effects of maintenance campaigns (three 4-week clusters of in-person group sessions) to a
self-directed program with educational information about maintenance. At a 12-month follow-up, participants in the clustered
campaigns maintained a significantly larger proportion of their initial weight losses than those in self-directed care (87% versus
71%, respectively).
In a trial with cancer survivors from rural communities, Befort and colleagues [48] tested the effects of extended care
delivered via 12 months of bi-weekly group telephone conference calls compared with informational newsletters. At an 18-month
follow-up, the group phone participants demonstrated significantly better maintenance of lost weight compared to participants in
the newsletter condition (73% versus 63%, respectively). Perri and colleagues [49] examined the effects of individual and group
telephone counseling compared to educational newsletters delivered via email. At the conclusion of the 12-month extended-care
period, only the individual phone counseling condition maintained a significantly greater percentage of lost weight compared
with the educational control group (101% versus 69%, respectively), and a significant between-group difference (73% versus
47%, respectively) remained evident at an 18-month follow-up.
Two studies examined the effects of providing continued contact to participants who had previously been randomized to face-
to-face programs of extended care. Vitolins and colleagues [50] randomized prior participants in extended care to either self-
directed care or to monthly face-to-face group maintenance sessions, coupled with monthly phone calls from a staff member.
After 48 months of additional follow-up, participants in continued care demonstrated significantly better maintenance of weight
loss compared to those in self-directed care (–5.7 versus +0.3 kg, respectively). Coughlin and colleagues [51] randomized

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participants who had previously received extended care via personal contacts to receive an additional 30-month program or no
further intervention. Participants who received the additional contacts did not experience any incremental weight-loss benefit
compared to those who had no further contact. Nonetheless, a small but statistically significant weight-loss advantage for
randomization to the in-person contact condition from the original trial was detected at the 66-month follow-up assessment.

25.3.3 Psychological Interventions

In recent years, attention has focused on the potential benefits of adding innovative psychological strategies to better equip
participants with skills to sustain the eating and exercise changes initiated during treatment and thereby produce better long-term
weight losses.
Knauper and colleagues [52, 53] examined the effects of teaching participants how to sustain behavioral changes using “if
–then” contingency plans to deal with lapses in diet or exercise. Participants were randomized to either a standard group-based
intervention or to an enriched intervention with supervised habit formation exercises consisting of individualized “if–then”
planning. No significant between-group differences in weight loss were observed at any point in the 24-month trial.
Daubenmier and colleagues [54] randomized participants to a standard lifestyle treatment or a lifestyle program coupled with
mindfulness-based stress reduction, mindfulness-based awareness procedures for eating and walking, and home-based practice of
meditation. No significant between-group differences in weight loss were observed at any time in the 18-month trial.
Acceptance and Commitment Therapy (ACT) includes strategies that are potentially relevant to weight management such as
mindful awareness and detachment from cravings and negative thoughts or feelings, acceptance of unwanted emotions and
cravings, clarification of life values related to body weight, and commitment to values-consistent behaviors in the presence of
cravings or difficult thoughts and feelings. Lillis et al. [55] randomized adults who had high internal disinhibition (i.e., prone to
eat in response to emotional or cognitive cues) to either an acceptance-based behavioral intervention (ABBI) or standard
behavioral treatment (SBT). At the conclusion of initial treatment and at a 24-month follow-up, mean weight losses were similar
across groups. However, the ABBI group regained significantly less weight than the SBT group (4.6 versus 7.1 kg, respectively),
suggesting that ABBI may help individuals with high internal disinhibition to maintain weight loss.
Lillis and colleagues [56] examined whether workshop training might serve as a novel and efficient approach to improving
weight-loss maintenance. The researchers randomized adults who had achieved weight losses >5% in an online weight-control
program to one of three conditions: (a) a 5-hour ACT-based maintenance workshop, (b) a 5-hour Self-Regulation (SR)-based
maintenance workshop, or (c) a no workshop control group. Participants in all three conditions received weekly emails during
months 3–6. The results showed no significant differences in weight loss between the ACT and SR conditions, but compared to
the control group, only the ACT intervention showed better maintenance of weight loss at month 24.
Finally, Butryn and colleagues [57] tested whether acceptance-based behavioral treatment coupled with an emphasis on
physical activity might improve the maintenance of lost weight. Following 6 months of standard behavioral treatment,
participants were randomized to one of three yearlong maintenance programs: (a) continued standard behavioral treatment, (b)
behavioral treatment plus an emphasis on exercise, or (c) acceptance-based behavioral treatment plus an emphasis on exercise. At
an 18-month assessment, no significant benefit was observed from the combination of acceptance-based treatment with an
emphasis on physical activity or from the combination of behavioral treatment with an emphasis on physical activity.

25.3.4 Technology-Based Interventions

In recent years, the proliferation of web-based applications and technologies to assist adults in making changes in their eating and
exercise regimens has grown dramatically [58, 59]. Several studies have examined whether technology-enhanced interventions
might improve long-term weight-loss outcomes.
Hageman and colleagues [60] randomized women from rural communities to (a) a web-based lifestyle intervention, (b) a web-
based lifestyle intervention plus peer support delivered via web-based discussion boards, or (c) a web-based lifestyle intervention
plus professional guidance delivered via email. Participants in all three conditions achieved >5% initial mean weight reductions
after 6 months of intervention. Weight regains over the next 24 months were similar across the three conditions, with no
significant advantage observed for the addition of either peer-led support or professional guidance via email.
Conroy and colleagues [61] tested whether electronic health record (EHR) based coaching might improve the maintenance of
lost weight. Adults with documented intentional weight losses >5% were randomly assigned to receive EHR tools to track their
diet, physical activity, and weight or to a program of 24 monthly personalized coaching contacts delivered through an EHR
portal. At month 24, participants in the EHR coaching condition maintained a significantly greater percentage of their initial lost
weight than those in the EHR tools condition (77% versus 52%, respectively).
Sniehotta and colleagues [62] examined the effectiveness of a low-intensity, technology-mediated intervention to enhance
weight-loss maintenance. Participants with documented losses >5% were randomly assigned to receive four quarterly newsletters
with lifestyle advice or a technology-enhanced program that included ongoing self-monitoring of diet and physical activity (via
an online interface) and weight (via wirelessly connected scales), coupled with text messages that provided tailored feedback
based on recent progress in meeting program goals. Over the course of 12 months, the mean weight regains in each condition
were virtually identical, with no evidence to suggest superior maintenance in the group that received the technology-enhanced
support.

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In a trial that provided a maintenance program tailored to men, Young and colleagues [63] randomized participants who had
lost >4 kg to a control group that received no additional resources or to a 6-month, gender-tailored maintenance program that
included a DVD containing weight-loss maintenance lessons, a self-monitoring log book, a pedometer, and free access to
websites for self-monitoring of diet and physical activity, coupled with weekly motivational text messages. No significant
between-group differences were evident at 1- or 3-year follow-ups.
Jakicic and colleagues [64] tested the hypothesis that compared with a standard treatment, a technology-enhanced weight-loss
intervention would result in greater long-term weight loss. Young adults (between the ages of 21–35 years) who completed
lifestyle treatment were randomly assigned to a “standard” intervention with web-based self-monitoring of diet and physical
activity or to a “technology-enhanced” intervention that included a wearable device and accompanying web interface to monitor
diet and physical activity. Contrary to the researchers’ hypothesis, the standard program demonstrated a significantly larger mean
weight loss at month 24 than the technology-enhanced intervention (5.9 versus 3.5 kg, respectively).

25.3.5 Pharmacological Interventions

Pharmacotherapy is commonly used to enhance the effectiveness of lifestyle interventions [3, 13]. Recent RCTs have examined
the long-term (>12 months) effects of cabergoline, semaglutide, and liraglutide. *
* Only studies that tested FDA approved medications at the time of this review were included.
Manning et al. [65] randomized adults who lost >5% of baseline weight following an 800 kcal/day commercial meal
replacement program to receive either 0.5 mg of cabergoline (a dopamine agonist) or a placebo for 24 months. Participants in
both conditions regained approximately two-thirds of their initial weight losses, and the between-group difference was not
significant.
Rubino and colleagues [66] examined the long-term effects of 2.4 mg/wk of injectable semaglutide (a GLP-1 receptor agonist)
on weight loss maintenance. During a 20-week run-in period, the participants received a lifestyle intervention plus semaglutide
and achieved a mean weight loss of 11.1 kg. The participants were subsequently randomized to either 48 weeks of semaglutide or
placebo. The semaglutide group lost an additional 7.1 kg, compared to a weight gain of 6.1 kg for the placebo group; the net
weight changes from baseline to follow-up were 18.2 versus 5.0 kg, respectively. Impressive weight-loss outcomes achieved with
semaglutide were also demonstrated by Wadden et al. [67] who randomly assigned adults with obesity to intensive behavioral
treatment plus semaglutide or intensive behavioral treatment plus placebo. Participants in both conditions received a low-calorie
diet (800 kcal/day) for 8 weeks and 30 sessions of intensive behavioral treatment over 68 weeks. At the conclusion of the trial,
the semaglutide group had a total weight loss of 17.1 kg compared to 5.1 kg for the placebo group. The amounts of weight loss
achieved and sustained by the semaglutide groups in the Rubino et al. and Wadden et al. studies are among the largest observed
for non-surgical interventions for weight loss.
Lundgren and colleagues [68] tested whether combining liraglutide (a GLP-1 receptor agonist) with moderate to vigorous
physical activity (MVPA) might improve long-term weight loss, as well as glycemic control, and cardiorespiratory fitness. The
researchers randomized adults who completed an 8-week low-calorie diet to one of four yearlong maintenance conditions: (a)
liraglutide + MVPA, (b) liraglutide + usual physical activity, (c) MVPA + placebo, or (d) usual physical activity + placebo
(control group). At the conclusion of the trial, all three active maintenance programs (groups a, b, and c) demonstrated greater
weight losses than the control group. Liraglutide + MVPA led to greater weight loss than MVPA + placebo but not greater than
liraglutide + usual physical activity. However, only the combined treatment of liraglutide + MVPA produced improvements in
glycemic control and cardiorespiratory fitness.

25.4 CONCLUSIONS
The findings from RCTs reviewed in this chapter generally support the AHA/ACC/TOS Guidelines [1], which recommend that
programs for the prevention of weight regain include a reduced-calorie diet, a high level of exercise, extended care by a trained
interventionist, and ongoing self-monitoring of weight and energy intake.

25.4.1 Reduced Calorie Diet

The Guidelines indicate that sustaining reduced caloric intake is crucial to maintaining lost weight. As demonstrated in two
recent trials [36, 37], a recommended calorie level of 1200–1500 kcal/d was effective for producing long-term weight loss, as
was the 5:2 intermittent fasting approach in which caloric intake is greatly reduced (500–600 kcal) on two non-consecutive days
of the week. Such findings suggest that the reduction in calorie intake does not necessarily need to occur on a daily basis, and
that the 5:2 intermittent fasting approach may serve as a reasonable alternative to continuous calorie restriction for some
participants. With respect to diet composition, the use of a high protein/low glycemic index diet did not improve weight loss
outcomes compared with a moderate protein/moderate glycemic index diet [43]. This finding is consistent with the
recommendation from the Guidelines that tailoring the macronutrient composition of the diet to participant preference may
enhance adherence and weight loss. An intriguing finding in one RCT was that the substitution of water for artificially sweetened
beverages improved the maintenance of lost weight [39].

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25.4.2 Exercise
The Guidelines recommend high levels of aerobic physical activity (>200 min/wk) for weight loss maintenance [1]. However,
much of the evidence supporting this recommendation is correlational in nature, showing that higher levels of exercise are
associated with greater maintenance of lost weight [40]. RCTs that prescribe higher levels of exercise commonly fail to show
effects based on randomized assignment, often due to poor adherence by participants to the regimen they were prescribed [40]. In
the current review, prescriptions for high-intensity exercise [43], higher volumes of exercise [42], and the inclusion of resistance
training [41], all failed to produce improvements in long-term weight loss.

25.4.3 Extended Care

Seven recent RCTs (involving 10 between-group comparisons) examined the long-term effects of extended care [45, 46, 47, 48,
49, 50, 51]. In 7 of the 10 comparisons, participants who received extended care achieved significantly greater long-term
maintenance compared to those assigned to educational control groups or self-directed care. Support was generally observed for
face-to-face contact with a trained interventionist, delivered on either a continuous basis [45, 46, 50, 51] or an intermittent
schedule involving clusters of sessions [47]. The effectiveness of extended care delivered via individual telephone counseling
was documented [49], but the data were mixed regarding the use of group conference calls for extended care [48, 49].

25.4.4 Self-Monitoring
Ongoing monitoring of weight, food intake, and physical activity is commonly associated with long-term success in weight
management [1, 3, 7]. Technological innovations have the potential to facilitate the tracking of key weight-management
behaviors [58, 59]. However, two RCTs [62, 64] failed to show the benefits of low-intensity technologies or wearable devices for
ongoing monitoring of diet or weight. Ongoing tracking alone may not be sufficient to enhance maintenance. The use of EHRs to
deliver personalized coaching produced significantly better maintenance of lost weight compared with the use of EHRs for
tracking without coaching [61]. Interestingly, the addition of professional guidance via email or group support via message
boards did not enhance the maintenance of weight loss for participants in a web-based lifestyle intervention [60] nor did the
inclusion of a technology resource pack that included access to a website for tracking diet and exercise combined with
motivational text messages [63]. Thus, the promise of technology-based interventions to enhance the maintenance of weight loss
largely remains unfulfilled.

25.4.5 Psychological Enhancements

The addition of specific psychological strategies such as enhanced habit formation [52, 53], mindfulness training [54], or
acceptance-based therapy [55, 57], whether delivered during initial treatment or follow-up, has not been shown to produce
improved weight-loss maintenance versus standard behavioral treatment. Secondary analyses from one trial [56] suggested that
acceptance-based therapy may reduce weight regain among individuals who are prone to eat in response to emotional or
cognitive cues.

25.4.6 Pharmacotherapy
The use of the centrally acting pharmacological agents, cabergoline [65] did not improve the maintenance of weight loss, but the
use of GLP-1 receptor agonists, liraglutide [68] and semaglutide [66, 67] did. These agents increase insulin production and slow
gastric emptying, thereby increasing satiety and decreasing appetite. The RCTs of semaglutide yielded particularly impressive
results, each with mean weight losses >17 kg after 68 weeks [66, 67]. The effects and side effects associated with longer-term
use of semaglutide have yet to be determined. Nonetheless, the success of semaglutide as a maintenance agent, as well as a
component of initial treatment, represents a significant advance toward the prevention of weight regain.

25.5 SUMMARY
This selective review of recent RCTs provides support for the effectiveness of two distinct approaches to weight-loss
maintenance. Structured programs of extended care provided by trained interventionists can help participants sustain lifestyle
changes in diet and exercise and thereby reduce the regaining of lost weight. Alternatively, the ongoing use of semaglutide,
increases satiety, decreases appetite, and produces large short- and long-term weight losses. Collectively, the findings from this
review indicate that with appropriate intervention, the prevention of weight regain following weight loss is indeed achievable.

ACKNOWLEDGMENTS
We thank Christian McLaren, Nancy Schaefer, Meena Shankar, and Pati Vial for their technical assistance in the preparation of
this chapter.

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