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 27一39.9 kg/m2. In coming several years, semaglutide, tirzepatide, and cargrilintide/semaglutide will become available for obesity treatment in Korea.
In 1971, Dr. Akira Endo succeeded in isolating a cholesterol synthesis inhibitor, compactin. Later, compactin was renamed mevastatin, meaning that it stops the synthesis of mevalonate, which is considered the first statin. However, mevastatin is not commercially released, whereas lovastatin, developed by Alfred Albert of Merk in 1979, was the first commercially developed statin. After the 4S study, the first largescale clinical trial with statins conducted in Scandinavia showed a dramatic secondary preventive effect against cardiovascular disease, and the effectiveness of statins in patients with dyslipidemia was repeatedly demonstrated. Subsequently, many oral drugs that affect blood lipid concentration; statins and ezetimibe aimed at reducing low-density lipoprotein (LDL)) cholesterol; fibrates and omega 3 formulations aimed at reducing triglycerides were widely developed and used in Korea. In this article, we review the results of clinical studies on representative cardiovascular diseases for four types of oral drugs for dyslipidemia, which are currently the most commonly used in Korea.
Dietary therapy is one of the most important treatments for obesity. In general, it is difficult to maintain the recommended diet for weight control for a long time; therefore, it is difficult to achieve weight loss or maintain weight. Intermittent fasting has recently become one of the most popular diets for weight loss. Intermittent fasting is a strategy of repeating intermittent energy restriction and eating, unlike conventional diets of continuous calorie restriction. Studies on intermittent fasting have shown positive results not only in terms of weight loss but also improvement in metabolic indicators, such as glucose control and reduction of blood pressure. Therefore, it is important to maintain a long-term dietary strategy to prevent weight loss in obese individuals. The effect on weight loss was similar to that of an existing continuous energy-restricted diet. However, long term studies and safety data are still lacking, and large-scale studies with various populations are needed. If more evidence is secured for various individuals, it can be expected that intermittent fasting, including time-restricted eating, will be applied clinically in the future.
Although it has been confirmed that excessive body fat increases health risks and all-cause mortality, several epidemiological studies have reported that overweight or obesity in patients with chronic diseases and in older adults is advantageous with respect to mortality. Several mechanisms have been proposed to explain the biological basis of this obesity paradox. The marked heterogeneity of findings observed across studies and the possibility of systematic errors in these studies have cast doubt on the actual existence of the obesity paradox. However, the obesity paradox questioned the validity of body mass index as the best indicator for obesity in terms of predicting its comorbidities and urges clinicians to focus more on changes in body composition and related metabolic derangements, rather than body weight per se.
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 obesepatients with major depressive disorder is complicated. Bariatric physicians shouldprovide 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 withliraglutide will be discussed. This report highlights the safety and efficacy of liraglutide treatment of obesity in patients with depression who take antidepressants and antipsychotics
Intensive lifestyle modifications and anti-obesity medications are essential for obesity treatment. Antiobesity medications should be selected according to the patient’s comorbidities, symptoms, and preferences. This case report describes the treatment of a morbidly obese patient with a history of depression, who complained of tingling and numbness after total thyroidectomy for papillary thyroid cancer. Very low-dose controlled-release phentermine/topiramate was prescribed and intensive lifestyle modifications were encouraged. As a result, the patient effectively lost weight and reached a near-normal weight without adverse drug effects. This implies that even an off-label anti-obesity medication low dose may be better for some patients, and the most important factor in obesity treatment is patient-tailored treatment.