Hormonal
Physiological adaptations to weight loss, including slowed resting metabolic rate (RMR) and increased hunger hormones, actively defend a higher body weight 'set-point' and promote weight regain.
After you lose weight, your body will fight to get it back by slowing your metabolism and increasing hunger. This is a biological 'set-point' defense, not a lack of willpower. To maintain weight loss, you must accept that you will need to be more vigilant about food intake and exercise than before, as your body is biologically programmed to regain the weight.
During periods of negative energy balance and reduced energy stores (weight loss), attempts are made to maintain homeostasis through hormonal signalling (eg, leptin and insulin) and other afferent neuronal signals relaying information to the brain (hypothalamus) to stimulate appetite and promote weight gain.
Why this rating
Well-established physiological principle supported by multiple studies cited (Biggest Loser, DIRECT study).
Source
Weight loss variability with SGLT2 inhibitors and GLP‐1 receptor agonists in type 2 diabetes mellitus and obesity: Mechanistic possibilities
Emily Brown et al. · Obesity Reviews · 2019
DOI 10.1111/obr.12841
More from this paper
- SGLT2 inhibitors produce significantly less weight loss than predicted by urinary glucose excretion because of compensatory hyperphagia (increased energy intake).Good
- GLP-1 receptor agonists exhibit significant inter-individual variability in weight loss, with early responders (>=4% loss at week 16) predicting superior long-term outcomes.Good
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
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