Patient initiation and maintenance of GLP-1 RAs for treatment of obesity

Patel, Dhiren; Smith, April

doi:10.1080/17512433.2021.1947796

Cited by 11 publications

(8 citation statements)

References 71 publications

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“…13 With regard to safety and tolerability, GLP-1RAs have been associated with GI tract-related AEs that are more frequent during dose escalation. 14 Similarly, in this study, orforglipron-treated participants reported more GI tract-related TEAEs than those who received placebo; however, these were not serious. Most of the GI tract-related AEs in orforglipron-treated participants occurred in the first week after initial dosing, indicating that the starting dose is as important as the frequency and magnitude of escalation.…”

Section: Discussionsupporting

confidence: 49%

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Orforglipron (LY3502970), a novel, oral non‐peptide glucagon‐like peptide‐1 receptor agonist: A Phase 1a, blinded, placebo‐controlled, randomized, single‐ and multiple‐ascending‐dose study in healthy participants

Pratt

Liu

et al. 2023

Diabetes Obesity Metabolism

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Aim: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of orforglipron (LY3502970), an oral, non-peptide glucagon-like peptide-1 receptor agonist (GLP-1RA) in healthy participants. Materials and Methods: This was a double-blind, placebo-controlled, Phase 1 study. Overtly healthy adults aged 18 to 65 years with body mass index of 20 to 40 kg/m 2 and glycated haemoglobin concentration of 47.5 mmol/mol (<6.5%) were eligible. In Part A, participants received single-dose orforglipron, with four cohorts receiving escalating doses (0.3-6 mg). In Part B, participants received 4 weeks of daily repeated oral orforglipron with doses escalating weekly to four different final target doses (2-24 mg). Results: Ninety-two participants enrolled and received at least one study drug dose (32 in Part A [mean age 43.4 years] and 60 in Part B [mean age 42.5 years]). The most common adverse events were gastrointestinal tract-related. Pharmacokineticswere approximately dose proportional, and the mean t 1/2 was 24.6 to 35.3 hours after a single dose (0.3-6 mg). On Day 28, the mean t 1/2 was 48.1 to 67.5 hours across the dose range (2-24 mg). Substantial reductions in body weight of up to 5.4 kg were observed after 4 weeks in orforglipron-treated participants, compared to a reduction of 2.4 kg with placebo (P < 0.05). Orforglipron decreased fasting glucose levels across Days 1 to 28, and gastric emptying was delayed on Day 28.Conclusions: Orforglipron's long half-life (25-68 hours) allows once-daily oral dosing, without water and food restrictions. Orforglipron had a pharmacodynamic and safety profile similar to that of injectable GLP-1RAs, which supports continued clinical development.

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Section: Discussionsupporting

confidence: 49%

“…With regard to safety and tolerability, GLP‐1RAs have been associated with GI tract‐related AEs that are more frequent during dose escalation 14 . Similarly, in this study, orforglipron‐treated participants reported more GI tract‐related TEAEs than those who received placebo; however, these were not serious.…”

Section: Discussionmentioning

confidence: 48%

Orforglipron (LY3502970), a novel, oral non‐peptide glucagon‐like peptide‐1 receptor agonist: A Phase 1a, blinded, placebo‐controlled, randomized, single‐ and multiple‐ascending‐dose study in healthy participants

Pratt

Liu

et al. 2023

Diabetes Obesity Metabolism

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“…Modern studies have confirmed the positive effect of Liraglutide in treating patients who have regained weight after bariatric surgery [ 44 ]. Recent studies confirm the positive effect of Liraglutide 3.0 mg on weight loss in patients and indicate a positive effect of the drug on the metabolism of myocardial cells [ 45 ]. New findings indicate the efficacy of Liraglutide 3.0 mg subcutaneously in obese patients [ 46 ].…”

Section: Novel Drugs In Obesity Treatmentmentioning

confidence: 96%

Pharmacological Treatments and Natural Biocompounds in Weight Management

et al. 2023

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The obesity pandemic is one of society’s most urgent public health concerns. One-third of the global adult population may fall under obese or overweight by 2025, suggesting a rising demand for medical care and an exorbitant cost of healthcare expenditure in the coming years. Generally, the treatment strategy for obese patients is largely patient-centric and needs dietary, behavioral, pharmacological, and sometimes even surgical interventions. Given that obesity cases are rising in adults and children and lifestyle modifications have failed to produce the desired results, the need for medical therapy adjunct to lifestyle modifications is vital for better managing obesity. Most existing or past drugs for obesity treatment target satiety or monoamine pathways and induce a feeling of fullness in patients, while drugs such as orlistat are targeted against intestinal lipases. However, many medications targeted against neurotransmitters showed adverse events in patients, thus being withdrawn from the market. Alternatively, the combination of some drugs has been successfully tested in obesity management. However, the demand for novel, safer, and more efficacious pharmaceutical medicines for weight management does exist. The present review elucidates the current understanding of the available anti-obesity medicines of synthetic and natural origin, their main mechanisms of action, and the shortcomings associated with current weight management drugs.

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“…Aiming at the treatment of obesity, according to Zizzari et al [ 8 ], the most sold peptide drug to treat metabolic diseases is liraglutide (Victoza ® ), an analog of glucagon-like peptide (GLP-1), resistant to degradation by the gastrointestinal tract enzyme dipeptidyl peptidase 4 (DPP-4). This analog prolongs the half-life of GLP-1 and, consequently, its action [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Encapsulated Peptides and Proteins with an Effect on Satiety

et al. 2023

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The world scenario has undergone a nutritional transition in which some countries have left the reality of malnutrition and now face an epidemic of excess body weight. Researchers have been looking for strategies to reverse this situation. Peptides and proteins stand out as promising molecules with anti-obesity action. However, oral administration and passage through the gastrointestinal tract face numerous physiological barriers that impair their bioactive function. Encapsulation aims to protect the active substance and modify the action, one possibility of potentiating anti-obesity activity. Research with encapsulated peptides and proteins has demonstrated improved stability, delivery, controlled release, and increased bioactivity. However, it is necessary to explore how proteins and peptides affect weight loss and satiety, can impact the nutritional status of obesity, and how encapsulation can enhance the bioactive effects of these molecules. This integrative review aimed to discuss how the encapsulation of protein molecules impacts the nutritional status of obesity. From the studies selected following pre-established criteria, it was possible to infer that the encapsulation of proteins and peptides can contribute to greater efficiency in reducing weight gain, changes in adipose tissue function, and lower hormone levels that modulate appetite and body weight in animals with obesity.

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Patient initiation and maintenance of GLP-1 RAs for treatment of obesity

Cited by 11 publications

References 71 publications

Orforglipron (LY3502970), a novel, oral non‐peptide glucagon‐like peptide‐1 receptor agonist: A Phase 1a, blinded, placebo‐controlled, randomized, single‐ and multiple‐ascending‐dose study in healthy participants

Orforglipron (LY3502970), a novel, oral non‐peptide glucagon‐like peptide‐1 receptor agonist: A Phase 1a, blinded, placebo‐controlled, randomized, single‐ and multiple‐ascending‐dose study in healthy participants

Pharmacological Treatments and Natural Biocompounds in Weight Management

Encapsulated Peptides and Proteins with an Effect on Satiety

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