Active Ingredient: Orlistat
Metrics details Abstract There is an urgent need for effective pharmacological therapies to help tackle the growing obesity epidemic and the healthcare crisis it poses.
The majority of these influence hypothalamic appetite pathways via dopaminergic or serotoninergic signalling. Among the 32 studies, 20 RCTs were included in the review of the benefits of weight loss medications KQ 1 and KQ 2, and all of the studies 30 RCTs, one retrospective cohort, and one event monitoring study were included in the review of potential harms of medications KQ 3.
Sample sizes ranged from 48 to 3731 in the RCTs median, 542. Fourteen studies had run-in periods to assess compliance with taking the medication.
The trials that examined health outcomes KQ 1 and KQ 2 lasted 12 to 48 months, with six trials contributing outcome data at 24 months or longer. The body of evidence regarding harms KQ 3 also included trials with shorter followup 1 to 6 months.
The retrospective cohort and event monitoring study examined harms over a median of 150 days to 3 years.
Five trials specifically reported conducting at least some communitywide recruitment via local advertising. No trial had eligibility criteria based on central adiposity i.We examined papers across a broad assess every published article addressing this psychosocial literature incorporating various types of studies, which are difficult to target relevant, and key literature regarding screening for hyperglycemia.
Baseline characteristics were similar in the two non-RCT studies. Increase resting or activity-related energy expenditure. Appetite reduction is the primary weight loss mechanism for the majority of current agents.
The arcuate nucleus of the hypothalamus plays a critical role in appetite regulation see Fig.
Because of the semipermeable blood—brain barrier in this region, peripheral signals indicative of energy balance—including glucose, insulin, leptin, a number of gut-derived factors including glucagon-like peptide-1 GLP-1, peptide YY PYY, oxyntomodulin and ghrelin—can directly interact with these neurons and influence feeding behaviour.
POMC neuronal activity is also modulated by dopaminergic and serotoninergic signalling from other brain regions and is therefore affected by a number of central nervous system CNS drugs that act on these neurotransmitters.
Of course, appetite is regulated not just by physiological energy status but also by environmental and emotional cues, such as the sight and smell of food. These reward-associated stimuli are integrated by the mesocorticolimbic reward system, with dopaminergic neurons originating in the ventral tegmental area VTA projecting to the nucleus accumbens and the prefrontal cortex, where they influence feeding behaviour.
Modulation of signalling in the dopaminergic reward system is also suggested as an additional mechanism for the action of some appetite suppressants.
Other pathways, including the reward circuitry, are involved in appetite and energy expenditure, but an understanding of the central role of the hypothalamus is useful in order to appreciate the mechanisms of action of several weight loss agents.
Well known as a source of non-shivering thermogenesis in human infants, it was assumed not to persist into adulthood, until review of positron emission tomography PET images from adult cancer patients revealed extensive glucose-avid areas in the neck and thorax, subsequently identified as brown fat.
BAT expresses high levels of uncoupling protein-1 UCP-1, which uncouples mitochondrial substrate utilization from ATP production, causing energy wastage.
Nevertheless, a variety of peripheral factors directly increase BAT activity, such as catecholamines, thyroid hormone, glucagon and fibroblast growth factor-21 FGF-21, raising the possibility of pharmacological manipulation.
This is relevant from a therapeutic point of view, as compensatory physiological and behavioural responses limit the weight loss that is achievable by any one mechanism.
Consequently, treatments that target both sides of the energy equation have the potential for greater effectiveness. Some studies have hinted at a possible minor role for BAT in mediating the effects of some newer anti-obesity agents, but its current status is primarily as an area of active research with potential future therapeutic application.
Instead, the focus should be on health benefits resulting from more modest weight loss.