Future Pharmacotherapy for Obesity: New Anti-obesity Drugs on the Horizon

Srivastava, Gitanjali; Apovian, Caroline M.

doi:10.1007/s13679-018-0300-4

Cited by 172 publications

(100 citation statements)

References 129 publications

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“…It also acts as an inhibitor of monoamine oxidase B (MAO-B), delays dopamine transporter reduction in Parkinson's disease, and alleviates Parkinsonian motor symptoms [20][21][22]. ZNS has also shown some efficacy as a treatment for migraine and obesity [23,24].…”

Section: Pharmacodynamicsmentioning

confidence: 99%

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An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy

Reimers

Ljung

2019

Expert Opinion on Pharmacotherapy

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Introduction: About 70 million people worldwide are estimated to suffer from epilepsy. Despite a large variety of old and new antiepileptic drugs on the market, about 30% of people with epilepsy do not become seizure-free with medical treatment. This is a major individual and public health burden. Most of these difficult-to-treat patients are having focal seizures. Zonisamide is effective against focal seizures in adults and children and, thus, a therapeutic option for such patients. Its safety profile needs special attention. Areas covered: Herein, the authors discuss the pharmacology, clinical efficacy and the adverse effects of zonisamide. The article is derived from clinical trial data, long-term studies, meta-analyses, review articles, text books, webpages, and official license information. Expert opinion: Zonisamide has proven to be efficacious in focal epilepsy in children and adults, although it is not more effective than carbamazepine or other antiepileptic drugs. It is also effective in generalized epilepsy and in several other conditions of the CNS. Its safety profile may prevent it from becoming a first-line drug for focal epilepsy or any other indication.

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Section: Pharmacodynamicsmentioning

confidence: 99%

“…In children, weight loss ≥5% has been observed in approximately 35% [65]. ZNS has been studied as an antiobesity drug but as yet it has not become an established treatment [24,66].…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy

Reimers

Ljung

2019

Expert Opinion on Pharmacotherapy

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“…Evidence from randomized controlled trials indicates the absence of an increased risk for pancreatitis or pancreatic cancer with GLP‐1 RAs (including semaglutide), whereas GLP‐1 RA‐induced thyroid C‐cell hyperplasia observed in animal models appears not to be applicable to humans . A recent meta‐analysis reported infrequent cases of acute pancreatitis with semaglutide .…”

Section: Safety Of Semaglutidementioning

confidence: 99%

“…Semaglutide has not been approved for the treatment of obesity, but development in this therapeutic field is ongoing . Few antiobesity drugs have been approved so far .…”

Section: Introductionmentioning

confidence: 99%

Semaglutide as a promising antiobesity drug

et al. 2019

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Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a long elimination half-life, allowing subcutaneous (sc) administration once per week. Both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) recently approved once-weekly sc semaglutide for the treatment of type 2 diabetes mellitus (T2DM). The weight loss efficacy of once-weekly sc semaglutide appears to be superior compared with the other once-weekly GLP-1 RAs in patients with T2DM. Semaglutide was recently evaluated as an antiobesity drug in a phase II dose-finding trial, which demonstrated superior weight loss efficacy of once daily sc semaglutide compared with both placebo and once daily 3.0 mg liraglutide in patients with obesity but without T2DM. The magnitude of semaglutide-induced weight loss in this study exceeded the criteria of both the EMA and FDA for antiobesity drugs, and there were no safety concerns, indicating the eligibility of once daily sc semaglutide as a future antiobesity drug.

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“…Although controversy exists, SST analogues have been used in diabetic retinopathy and hypothalamic obesity [208,209]. Currently, the efficacy of SST and its analogues in obesity is being evaluated in various clinical studies [9,20,210,211].…”

Section: Somatostatin and Obesitymentioning

confidence: 99%

Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity

Kumar

Singh

2020

IJMS

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Obesity is one of the major social and health problems globally and often associated with various other pathological conditions. In addition to unregulated eating behaviour, circulating peptide-mediated hormonal secretion and signaling pathways play a critical role in food intake induced obesity. Amongst the many peptides involved in the regulation of food-seeking behaviour, somatostatin (SST) is the one which plays a determinant role in the complex process of appetite. SST is involved in the regulation of release and secretion of other peptides, neuronal integrity, and hormonal regulation. Based on past and recent studies, SST might serve as a bridge between central and peripheral tissues with a significant impact on obesity-associated with food intake behaviour and energy expenditure. Here, we present a comprehensive review describing the role of SST in the modulation of multiple central and peripheral signaling molecules. In addition, we highlight recent progress and contribution of SST and its receptors in food-seeking behaviour, obesity (orexigenic), and satiety (anorexigenic) associated pathways and mechanism.Contrary to obesity, satiety is a sense of fullness due to ephemeral lack of interest in further ingestion of food, which eventually leads to the suppression of appetite. Fullness is supposed to have a vital role in weight management because it will impact the frequency and amount of food and drink consumed later [53]. The feeling of satiety is a well-organized and biologically oriented process [54,55]. Satiety is a well-articulated process which reduces gastric distension and cholecystokinin (CCK) release in gut post ingestion of nutrients and importantly has been associated with signals from periphery via vagal afferent fibers that terminate in nucleus of the tractus solitaries (NTS) in the brain stem [56]. Besides, leptin, a hormone secreted by adipocytes, is also associated with satiety signals and studies further indicate that satiety response to CCK that was blocked in leptin receptor-deficient rat was regained following restoration of the leptin receptor in arcuate nucleus (ARC) [57][58][59]. Studies also support the role of NTS vagus afferent in response to leptin [60,61]. Feeling satiated will, in the long run, smother the inclination for cravings and lead to lesser consumption of food in the next meal. Satiety is not a response; it involves a complex mechanism for its operation, which includes the crucial role of the hypothalamus and peripheral hormones and determines energy expenditure [62]. Measurement of satiation can be done either directly by assessing food intake or indirectly by subjectively rating the urge for appetite [63]. Schwartz et al. demonstrated that hypothalamus is the central brain region responsible for adiposity signal; however, it is not an active participant in satiety [64]. It is interesting to note that most satiety associated information is relayed to NTS afferent fibers from the vagus nerve and afferent from GIT through the spinal cord. Mechanical or chemical stimula...

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Future Pharmacotherapy for Obesity: New Anti-obesity Drugs on the Horizon

Cited by 172 publications

References 129 publications

An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy

An evaluation of zonisamide, including its long-term efficacy, for the treatment of focal epilepsy

Semaglutide as a promising antiobesity drug

Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity

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