• Mass Spectrometry Letters
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• 제14권4호
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• pp.141-146
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• 2023

Liraglutide is a medication prescribed for the management of type 2 diabetes and chronic obesity. A simple, sensitive, and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative analysis of liraglutide in rat plasma. After a simple protein precipitation step, liraglutide was chromatographically separated using the ACQUITY Premier Peptide BEH C18 Column with mobile phases comprising 50% acetonitrile and 50% methanol, and water with 0.3% FA. Positive ion electrospray ionization in multiple reaction monitoring mode was used to achieve detection. Good linearity was observed in the 5-600 ng/mL concentration range (R² > 0.99). Liraglutide had intra- and inter-day precision values of 2.13%-9.86% and 4.14%-8.36%, respectively. The accuracy ranged from -2.36% to 2.58%. The recovery and matrix effect were within acceptable limits. This selective LC-MS/MS method was used to study the pharmacokinetic properties of liraglutide after subcutaneous administration in rats.

• Molecules and Cells
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• 제41권3호
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• pp.234-243
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• 2018

In recent years, the interest towards the relationship between incretins and bone has been increasing. Previous studies have suggested that glucagon-like peptide-1 (GLP-1) and its receptor agonists exert beneficial anabolic influence on skeletal metabolism, such as promoting proliferation and differentiation of osteoblasts via entero-osseous-axis. However, little is known regarding the effects of GLP-1 on osteoblast apoptosis and the underlying mechanisms involved. Thus, in the present study, we investigated the effects of liraglutide, a glucagon-like peptide-1 receptor agonist, on apoptosis of murine MC3T3-E1 osteoblastic cells. We confirmed the presence of GLP-1 receptor (GLP-1R) in MC3T3-E1 cells. Our data demonstrated that liraglutide inhibited the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, as detected by Annexin V/PI and Hoechst 33258 staining and ELISA assays. Moreover, liraglutide upregulated Bcl-2 expression and downregulated Bax expression and caspase-3 activity at intermediate concentration (100 nM) for maximum effect. Further study suggested that liraglutide stimulated the phosphorylation of AKT and enhanced cAMP level, along with decreased phosphorylation of $GSK3{\beta}$, increased ${\beta}-catenin$ phosphorylation at Ser675 site and upregulated nuclear ${\beta}-catenin$ content and transcriptional activity. Pretreatment of cells with the PI3K inhibitor LY294002, PKA inhibitor H89, and siRNAs GLP-1R, ${\beta}-catenin$ abrogated the liraglutide-induced activation of cAMP, AKT, ${\beta}-catenin$, respectively. In conclusion, these findings illustrate that activation of GLP-1 receptor by liraglutide inhibits the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation through $cAMP/PKA/{\beta}-catenin$ and $PI3K/Akt/GSK3{\beta}$ signaling pathways.

• 비만대사연구학술지
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• 제1권2호
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• pp.78-82
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• 2022

Liraglutide (Saxenda^R) is prescribed to induce and sustain weight loss in obese patients. The starting dose of liraglutide is 0.6 mg/day for 1 week, which is increased by 0.6 mg/day every week until the full maintenance dose of 3 mg/day is achieved. Such dose titration is needed to prevent side effects, which primarily include gastrointestinal problems such as nausea, diarrhea, constipation, vomiting, dyspepsia, and abdominal pain. A 35-year-old, reportedly healthy obese man receiving liraglutide treatment for obesity visited the emergency room complaining of generalized weakness and dizziness accompanied by repeated diarrhea and vomiting. He reported over 20 episodes of diarrhea starting the day after liraglutide dose escalation from 1.2 mg/day to 1.8 mg/day. Laboratory findings suggested pre-renal acute kidney injury, including serum creatinine 4.77 mg/dl, blood urea nitrogen (BUN) 37 mg/dl, estimated glomerular filtration rate (eGFR) 15 ml/min/1.73 m², and Fractional excretion of sodium 0.08. After volume repletion therapy, his renal function recovered to a normal range with laboratory values of creatinine 1.08 mg/dl, BUN 14 mg/dl, and eGFR 88 ml/min/1.73 m². This case emphasizes the need for caution when prescribing glucagon-like peptide-1 receptor agonists, including liraglutide, given the risk of serious renal impairments induced by volume depletion and dehydration through severe-grade diarrhea and vomiting.

• 비만대사연구학술지
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• 제1권1호
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• pp.39-42
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• 2022

Obesity is a chronic disease associated with severe complications. A major complication of obesity is depression, which can worsen obesity and vice versa. In addition, most antidepressants or antipsychotics cause weight gain, and the relationship between obesity and depression is clinically critical. However, treatment of obese patients with major depressive disorder is complicated. Bariatric physicians should provide appropriate behavioral interventions alongside pharmacological treatment, considering psychiatric symptoms, drug side effects, and drug interactions. Two successful cases of moderate-to-severe obese patients with major depressive disorder who had been treated for obesity using behavioral intervention therapy along with liraglutide will be discussed. This report highlights the safety and efficacy of liraglutide treatment of obesity in patients with depression who take antidepressants and antipsychotics.

• 비만대사연구학술지
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• 제2권2호
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• pp.71-75
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• 2023

Obesity is closely related to chronic diseases and cancer. The present case report aims to discuss the anti-obesity treatment strategy and the evaluation of the clinical progress in a patient with obesity and concurrent fatty liver disease. Following five months of treatment with liraglutide and rosuvastatin, the patient had a weight reduction of 3 kg (4.7%), a decrease in fasting blood sugar by 42 mg/dl (26.6%), a decrease in low-density lipoprotein cholesterol by 82 mg/dl (60.2%), and decrease in alanine transaminase. This case report documented the treatment of a patient with common chronic diseases encountered in the outpatient setting. Based on the therapeutic effects documented in clinical and laboratory indices, the anti-obesity treatment plan significantly aided in managing chronic diseases.

• 비만대사연구학술지
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• 제1권1호
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• pp.4-13
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• 2022

Currently, pharmacotherapy is becoming essential for obesity, owing to its expanding and increasing epidemiology. In this review, novel peptide-based drugs of four classes are covered: GLP-1 receptor agonist, GIP/GLP-1 receptor dual agonist, glucagon/GLP-1 receptor dual agonist, and a combination of amylin receptor agonist/GLP-1 receptor agonist. Semaglutide is a next-generation GLP-1 receptor agonist with a longer duration and stronger weight and glucose reduction effects than liraglutide and dulaglutide. In the STEP1 trial, semaglutide 2.4 mg reduced body weight by approximately 15% in people with obesity with similar or milder adverse events than liraglutide 3.0 mg. Tirzepatide, a GIP/GLP-1 receptor dual agonist, also has a long duration and strong weight- and glucose-lowering effect. According to SURPASS-2, 3, and 4, in patients with BMI≥25 kg/m² and type 2 diabetes mellitus (T2DM), tirzepatide 15 mg reduced the initial body weight by >13%. Cotadutide, a glucagon/GLP-1 receptor dual agonist, showed weaker weight-lowering effects than semaglutide and tirzepatide, while it was comparable to that of liraglutide in a phase 2 clinical trial for non-alcoholic fatty liver disease in patients with BMI≥25 kg/m² and T2DM. Additionally, its effect on the liver was noticeable. The long-acting amylin receptor agonist cargrilintide combined with semaglutide can be another effective option for obesity treatment. Even in a small phase 1 trial with a short study period of 20 weeks, cargrilintide 2.4 mg/semaglutide 2.4 mg reduced by 17% of initial body weight in people with BMI 27-39.9 kg/m². In coming several years, semaglutide, tirzepatide, and cargrilintide/semaglutide will become available for obesity treatment in Korea.

• 비만대사연구학술지
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• 제3권1호
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• pp.27-34
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• 2024

The prevalence of obesity in children and adolescents is increasing worldwide. Obesity in children and adolescents not only increases the risk of transitioning to obesity in adulthood but also increases the risk of cardiometabolic diseases such as high blood glucose, high blood pressure, dyslipidemia, fatty liver, and hyperinsulinemia during childhood. The goal of treating obesity in children and adolescents is not to focus on weight loss but to help children reach a healthy weight while maintaining normal growth appropriate for their age and sex. To achieve this goal, regular physical activity and exercise, dietary modification, improvement of obesity-prone environmental factors, and behavioral changes are required for a healthy lifestyle. If appropriate weight control is not achieved through lifestyle modifications, pharmacotherapy may be considered for adolescents with severe obesity aged 12 and above. Recent clinical trials have reported the efficacy and safety of pharmacotherapy in severely obese adolescents. Currently, two medications can be prescribed in Korea for patients with obesity aged 12 and above: Orlistat and Liraglutide. However, despite effective weight control through drug treatment, body weight may increase again after treatment discontinuation. Therefore, it is crucial to evaluate adherence to health behaviors during visits and continue to educate on lifestyle modifications, even during pharmacotherapy, to minimize weight regain.

• 한국임상약학회지
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• 제21권2호
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• pp.57-65
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• 2011

Incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide delay gastric emptying, increasing satiety, and enhance insulin secretion. Two new classes of treatments related to incretin hormones for the management of type 2 diabetes mellitus have emerged: GLP-1 receptor agonists (e.g., exenatide, liraglutide) and the dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin, saxagliptin, vildagliptin, alogliptin), which prevent the degradation of GLP-1. A MEDLINE search was conducted in order to evaluate the efficacy and safety of incretin-based therapies and publications were reviewed. Data from clinical trials indicated incretin-based treatment showed clinically significant reductions in hemoglobin A1c with low risk of hypoglycemia. Weight reductions were observed with GLP-1 receptor agonists where as DPP-4 inhibitors are weight neutral.

• The Korean Journal of Medicine
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• 제93권6호
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• pp.501-508
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• 2018

Obesity is a chronic disorder that is a significant risk factor for diabetes, cardiovascular diseases, malignancy, and other chronic diseases. Lifestyle modifications form the basis of most treatments for obesity, but it has become clear that such modifications alone are not enough for many obese patients. When a behavioral approach is insufficient, pharmacological treatment may be recommended. In recent years, the US Food and Drug Administration (FDA) has withdrawn several therapeutic options for obesity due to their side effects, but has approved four novel anti-obesity agents. Until recently, orlistat was the only drug approved for the management of long-term obesity, but the US FDA approved the novel anti-obesity drugs lorcaserin and phentermine/topiramate in 2012, and naltrexone/bupropion and liraglutide in 2014. The present review discusses the different pharmacotherapeutic options for the treatment of obesity.

• 생명과학회지
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• 제31권11호
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• pp.1037-1045
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• 2021

전세계적으로 비만의 유병률은 증가하고 있으며 비만 유행은 식이요인과 좌식 생활 방식과 관련이 있기 때문에 현대인에게 발병하기 쉬운 질병이다. 또한 비만은 당뇨병, 심혈관계 질환과 같이 심각한 합병증을 동반하기 때문에 비만을 예방하고 치료하는 것이 중요해지고 있다. 현재 Liraglutide와 phentermine과 같은 의약품이 식욕억제 및 위장관 운동 지연을 유도해 비만 치료를 하고자 사용되고 있지만 갑상선암, 심혈관계 부작용, 중추 신경계 부작용 등 다양한 부작용이 발생하는 것으로 알려져있다. 따라서 상대적으로 부작용이 적은 비만 치료 방법을 탐색하기 위해 백색 지방조직을 갈색조직지방으로 바꾸어 에너지 소비를 증가시켜 비만을 치료하는 "Fat browning"이라는 방법이 도입되었다. 임상적으로 안전하게 "browning"을 유도하기 위해 효과 있는 천연 물질을 탐색하기 위한 연구가 진행중이며 현재 많은 천연물 소재가 연구되었다. 천연 물질 치료를 통한 "Browning" 유도는 일반적으로 "Browning" 유도 인자의 긍정적인 제어, 백색지방조직으로의 분화 억제, "Browning"과 관련된 메커니즘의 활성화의 세 가지를 포함한다. 따라서 Strawberry, Black raspberry, Cinnamomum cassia, Ecklonia stolonifera와 같은 "Browning" 유도 효과가 알려진 식물 추출물에 대한 연구를 설명한다. 우리는 또한 이러한 추출물이 "Browning"을 유도하고 그들이 매개하는 신호 경로를 통해 지금까지 확인된 메커니즘을 요약한다. 나아가 Browning을 통해 생성된 갈색지방조직이 내분비 기관으로써 심장 질환에 미치는 영향까지 확인해본 후 정리했다.