Proportional Feedback Control of Energy Intake During Obesity Pharmacotherapy

Hall, Kevin D.; Sanghvi, Arjun; Göbel, Britta

doi:10.1002/oby.21978

Cited by 22 publications

(43 citation statements)

References 26 publications

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“…Metformin therapy is not known to significantly alter energy expenditure (25, 32). It is well recognized that the human body adapts to weight loss with compensatory neuronal, hormonal, and metabolic changes that promote weight regain (33–36). Whether metformin counters some of these compensatory changes is a subject for further investigation.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study

et al. 2019

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Background: Identifying reliable predictors of long-term weight loss could lead to improved weight management. Objective: To identify predictors. Design: The Diabetes Prevention Program (DPP) was a randomized controlled trial that compared weight loss using placebo, intensive lifestyle intervention, or metformin, and its Outcomes Study (DPPOS) observed patients after the masked treatment phase ended. Setting: 27 DPP/DPPOS clinics. Participants: Of the 3234 randomized participants, 1066 lost ≥ 5% of their baseline weight during the first year and have been followed for 15 years. Measurements: Treatment assignment, personal characteristics, and weight. Results: After 1 year, 289 (28.5%) metformin participants, 640 (62.6%) intensive lifestyle participants, and 137 (13.4%) placebo participants, achieved ≥ 5% weight loss. After the masked treatment phase ended, the mean (95% CI) amount of weight loss relative to baseline that was maintained between years 6 and 15 was 6.2% (5.2, 7.2) for metformin participants, 3.7% (3.1, 4.4) for intensive lifestyle participants, and 2.8% (1.3, 4.4) for placebo participants. Independent predictors of long-term weight loss included greater weight loss during the first year in all study groups, older age and continued use of metformin in the metformin group, older age and not having diabetes or a family history of diabetes in the intensive lifestyle group, and higher baseline fasting plasma glucose in the placebo group. Limitation: Post-hoc analysis. Nonrandomized subsets of randomized groups examined after year 1. Conclusion: Among those with ≥ 5% 1-year weight loss, the group originally randomized to metformin had the greatest success with weight loss during years 6–15. Older age and the amount of initial weight loss were the most consistent predictors for maintaining long-term weight loss. Primary Funding Source: National Institutes of Health. Trial Registration: ClinicalTrials.gov and .

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Section: Discussionmentioning

confidence: 99%

Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study

et al. 2019

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“…This study and the modelling of responses to WL pharmacotherapy (22) suggests that prolonged WL attempts lead to a prolonged and exponential increase in appetite (using estimated EI as a proxy) in proportion to the weight that is lost (21) . Reports of changes in peripheral appetite peptides in response to 10-20% WL produce results that can be interpreted as being consistent with WL increasing homeostatic increases in appetite (43; 44; 47; 49; 50) .…”

Section: Very High Levels Of Ad Libitum Ei In Response To Prior Semi-mentioning

confidence: 83%

Developing evidence-based behavioural strategies to overcome physiological resistance to weight loss in the general population

et al. 2019

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Physiological and behavioural systems are tolerant of excess energy intake and responsive to energy deficits. Weight loss (WL) changes body structure, physiological function and energy balance (EB) behaviours, which resist further WL and promote subsequent weight regain. Measuring and understanding the response of EB systems to energy deficits is important for developing evidence-based behaviour change interventions for longer-term weight management. Currently, behaviour change approaches for longer-term WL show modest effect sizes. Self-regulation of EB behaviours (e.g. goal setting, action plans, self-monitoring, relapse prevention plans) and aspects of motivation are important for WL maintenance. Stress management, emotion regulation and food hedonics may also be important for relapse prevention, but the evidence is less concrete. Although much is known about the effects of WL on physiological and psychological function, little is known about the way these dynamic changes affect human EB behaviours. Key areas of future importance include (i) improved methods for detailed tracking of energy expenditure, balance and by subtraction intake, using digital technologies, (ii) how WL impacts body structure, function and subsequent EB behaviours, (iii) how behaviour change approaches can overcome physiological resistance to WL and (iv) who is likely to maintain WL or relapse. Modelling physiological and psychological moderators and mediators of EB-related behaviours is central to understanding and improving longer-term weight and health outcomes in the general population.

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“…42 This is opposite to the experience with obesity drugs, which have declining drug efficacy/effectiveness over time, often culminating in a weight-loss plateau within *1 year. 190 Further, because T is a key metabolic hormone, by correcting TD, TTh creates a metabolic environment that facilitates fat loss and long-term maintenance of an improved body composition.…”

Section: Discussionmentioning

confidence: 99%

Testosterone Therapy for Prevention and Treatment of Obesity in Men

Caliber

Saad

2020

Androgens: Clinical Research and Therapeutics

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Testosterone deficiency (TD) is common in men with obesity. The association between TD and obesity is bidirectional; low testosterone (T) is a contributing cause to obesity, and obesity is a contributing cause to low T, creating a vicious circle. Most guidelines recommend weight loss by diet/exercise as the first point of intervention to stop this vicious cycle. However, it requires a large amount of weight loss that is maintained over time. In clinical practice, this is rarely achieved by lifestyle interventions. Bariatric surgery is currently the main obesity treatment modality that results in a large amount of weight loss with decent weight loss maintenance. However, bariatric surgery is an invasive and expensive procedure, with risk for complications. Considering the high prevalence of TD in men with obesity, a more practical and sustainable obesity treatment for men is testosterone therapy (TTh). Thanks to the metabolic effects of T, TTh results in more fat loss and preservation of fatfree mass, compared with diet/exercise interventions alone. In contrast to weight loss achieved by diet/exercise and bariatric surgery, TTh significantly preserves both muscle and bone mass. Further, TTh has psychological effects that may increase the motivation and ability of men to adhere to diet/exercise programs. Real-world evidence studies of long-term TTh for up to 11 years provide compelling evidence that TTh holds tremendous potential as a new treatment modality for obesity in men, with long-term weight loss maintenance and health benefits far exceeding those achieved by lifestyle interventions, approved obesity drugs, as well as bariatric surgery.

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Proportional Feedback Control of Energy Intake During Obesity Pharmacotherapy

Cited by 22 publications

References 26 publications

Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study

Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study

Developing evidence-based behavioural strategies to overcome physiological resistance to weight loss in the general population

Testosterone Therapy for Prevention and Treatment of Obesity in Men

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