An update on pharmacotherapeutic strategies for obesity

Tchang, Beverly G.; Tarazi, Mohamad Sirri; Aras, Mohini; Shukla, Alpana

doi:10.1080/14656566.2021.1888927

Cited by 8 publications

(5 citation statements)

References 74 publications

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“…Despite these negative effects, Setmelanotide has demonstrated promise in treating childhood and adolescent obesity associated with genetics. Tirzepatide and Cotadutide, dual gastrointestinal peptide modulators of GLP-1 and either glucose-dependent insulinotropic polypeptide (GIP) or glucagon receptors, have phase 2 data suggesting efficient weight loss in particular groups [49]. Monoclonal antibody against skeletal myoblast activin type 2 receptors, Bimagrumab is a first-inclass innovative AOM.…”

Section: Discussionmentioning

confidence: 99%

“…Monoclonal antibody against skeletal myoblast activin type 2 receptors, Bimagrumab is a first-inclass innovative AOM. Its phase 2 trial concentrated on the endpoint of fat mass loss rather than total body weight loss [49][50]. In a phase 1 research, retatrutide, a single peptide having agonist action at the glucose-dependent insulinotropic polypeptide (GIP), GLP-1, and glucagon receptors, significantly reduced blood sugar levels and body weight [55].…”

Section: Discussionmentioning

confidence: 99%

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Shedding light on weight loss: A narrative review of medications for treating obesity

Darapaneni,

Lakhanpal,

Chhayani

et al. 2024

Romanian Journal of Internal Medicine

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Obesity and overweight are the major risk factors for numerous chronic diseases, including cardiovascular diseases such as heart disease and stroke, which are the leading causes of death worldwide. The prevalence of obesity has dramatically risen in both developed and developing countries, making it a significant public health concern and a global crisis. Despite lifestyle modifications being the first-line treatment, the high risk of relapse has led to a growing interest in non-invasive pharmacotherapeutic interventions to achieve and maintain weight loss and reverse the growth of the obesity epidemic. Cardiovascular diseases and cancer account for the highest mortality rates among other comorbidities associated with obesity and overweight. Excess and abnormally deposited adipose tissue secretes various inflammatory mediators, leading to cardiovascular diseases and cancers. Weight loss of 5-10% significantly reduces cardiometabolic risk. Medications currently approved in the USA for long-term management of obesity are orlistat, naltrexone, bupropion, phentermine/topiramate, and Glucagon Like Peptide-1 (GLP-1) agonists such as liraglutide and semaglutide. The benefit-to-risk of medications, comorbidities, and individual responses should guide the treatment decisions. The article provides a comprehensive overview and discussion of several weight loss medications used previously and currently, including their efficacy, mechanisms of action, and side effects.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Shedding light on weight loss: A narrative review of medications for treating obesity

Darapaneni,

Lakhanpal,

Chhayani

et al. 2024

Romanian Journal of Internal Medicine

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show abstract

“…Obesity and type 2 diabetes mellitus (T2DM) are prevalent chronic diseases around the world that are significantly harmful to human well-being and cause a substantial Biology 2024, 13, 63. https://doi.org/10.3390/biology13010063 https://www.mdpi.com/journal/biology economic burden on healthcare systems [1,2]. There is a certain connection between obesity and diabetes, since they are both involved in the disorder/imbalance of glucolipid metabolism, and obesity management can reduce the possibility of prediabetes developing into type 2 diabetes [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…The clinical drugs for treating obesity include pancreatic lipase inhibitors, glucagon-like peptide 1 (GLP1) receptor agonists and dual agonists for GLP1 and glucose-dependent insulinotropic peptide (GIP) receptors, γ-aminobutyric acid (GABA) A type receptor activators, serotonin 2C receptor agonists, opioid antagonists, dopamine-norepinephrine reuptake inhibitors, etc. [12][13][14]. At present, there is no way to completely cure type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Hyperglycemia and Hyperlipidemia by Blocking Toll-like Receptor 4: Comparison of Wild-Type and Toll-like Receptor 4 Gene Knockout Mice on Obesity and Diabetes Modeling

Zhao,

Zheng,

Wang

et al. 2024

Biology

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Innate immune receptor TLR4 plays an important role in glycolipid metabolism. The objective of this study is to investigate the inhibitory effects of blocking TLR4 on hyperglycemia and hyperlipidemia by comparing WT and TLR4−/− mice in obesity and diabetes modeling. The knockout of the TLR4 gene could prevent weight gain induced by a high-fat diet (HFD)/high-sugar and high-fat diet (HSHFD), and the differences in the responses existed between the sexes. It extends the time required to reach the obesity criteria. However, when mice were injected with intraperitoneal streptozotocin (STZ) after being fed by HSHFD for two months, TLR4−/− mice exhibited less weight loss than WT. Blocking TLR4 alleviated the changes in body weight and blood glucose, consequently reducing the efficiency of diabetes modeling, especially for male mice. Additionally, male TLR4−/− obese mice exhibit lower total cholesterol (TC) and low-density lipoprotein (LDL) levels in serum and less formation of fat droplets in the liver compared to WT. On the other hand, the knockout of TLR4 significantly increased the high-density lipoprotein (HDL) of male mice. This study should provide new insights into the role of TLR4, as well as opportunities to target novel approaches to the prevention and treatment of metabolic diseases like obesity and diabetes.

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“…Consequently, therapeutic approaches to combat obesity-associated disorders should include strategies to restore mitochondrial function 18 . Although some weight-loss drugs have been developed, they often do not work well or have serious side effects 2,19,20,21,22 . Therefore, there is an urgent need to develop new drugs for the treatment of obesity and its complications.…”

Section: Introductionmentioning

confidence: 99%

The cyclin dependent kinase inhibitor Roscovitine reverses diet- induced metabolic disruption in obese mice

Rabhi

Desevin

Cortez

et al. 2021

Preprint

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Most strategies to treat obesity-related disorders have involved prevention of diet-induced weight gain in lean mice. Treatment of obese individuals will require therapies that reverse the detrimental effects of excess body weight. Here, we show that roscovitine given to mice during the last six weeks of a 19-week high fat diet, reduced weight gain and prevented accompanying insulin resistance, hepatic steatosis, visceral adipose tissue (eWAT) inflammation/fibrosis as well as restored insulin secretion and enhanced whole body energy expenditure. Proteomics and phosphoproteomics analysis of eWAT demonstrated that roscovitine suppressed expression of peptides and phosphopeptides linked to inflammation and extracellular matrix proteins. It also identified 17 putative protein kinases perturbed by roscovitine, including CMGC kinases, AGC kinases and CAMK kinases. Pathway enrichment analysis showed that lipid metabolism, TCA cycle, fatty acid beta oxidation and creatine biosynthesis are enriched following roscovitine treatment. For brown adipose tissue (BAT), analysis of upstream kinases controlling the phosphoproteome revealed two major kinase groups, AGC and CMGC kinases. Among the top enriched pathways were insulin signaling, regulation of lipolysis in adipocytes, thyroid hormone signaling, thermogenesis and cAMP-PKG signaling. We conclude that roscovitine is effective at reversing prolonged diet-induced metabolic disruption and restoring mitochondrial activity in BAT and eWAT.

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An update on pharmacotherapeutic strategies for obesity

Cited by 8 publications

References 74 publications

Shedding light on weight loss: A narrative review of medications for treating obesity

Shedding light on weight loss: A narrative review of medications for treating obesity

Inhibition of Hyperglycemia and Hyperlipidemia by Blocking Toll-like Receptor 4: Comparison of Wild-Type and Toll-like Receptor 4 Gene Knockout Mice on Obesity and Diabetes Modeling

The cyclin dependent kinase inhibitor Roscovitine reverses diet- induced metabolic disruption in obese mice

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