History of drugs for weight loss
In 1760, English physician Malcolm Flemyng was the first to refer to obesity as a disease. The public’s view of obesity could shift if it were viewed as a medical condition rather than a social parameter. People are considered overweight if their body mass index (BMI) is 25 or higher, and obese if it’s 30 or higher. The World Health Organization (WHO) estimates that over 1 billion people around the world are obese, putting them at a higher risk of various health complications. Diabetes mellitus, cardiovascular disease, hypertension, stroke, decreased female fertility, mental health issues, worse COVID-19 outcomes, and an increased risk of cardiovascular disease are all linked to obesity. In the United States, anti-obesity drugs have a long and storied past. Until the US Food and Drug Administration (FDA) banned amphetamines as a weight-loss aid in 1979 due to their addictive potential, they were extensively promoted for their ability to suppress hunger during the post-war era. After that, fen-phen, a diet pill that combined the anorectics phentermine and fenfluramine, had a meteoric rise to fame in the mid-1990s. However, the FDA eventually took the product from shelves on concerns about major heart valve issues. Meridia, Acomplia, and Ephedra were all removed off pharmacy shelves due to inconsistent safety records, indicating that more recent attempts have not fared any better.
Efficacy of currently approved medications for obesity
Currently, five drugs have been authorized by the FDA for the treatment of obesity. Lorcaserin was the sixth medicine to be licensed for weight reduction, but it was removed after eight years of clinical usage because of concerns about an increased risk of cancer.
Orlistat: Orlistat, an inhibitor of pancreatic and stomach lipases, can reduce fat absorption by 30% and aid in weight loss. Results showing a decrease in BMI, weight, waist circumference, total cholesterol, and low-density lipoprotein (LDL) cholesterol were obtained by Yu et al. when orlistat was administered in conjunction with a healthy diet or diet plus exercise rather than diet alone. Researchers Khera et al. discovered that compared to those given a placebo, those given orlistat were more likely to lose 5% of their starting weight (Odds ratio (OR) 2.70, 95% credible interval (CrI) 2.34-3.09, surface under the cumulative ranking curve (SUCRA) 0.22). Orlistat resulted with 2.6 kg more weight reduction at one year compared to placebo (95% CrI -3.04 to -2.16 kg). Over the course of seven months, the XENSOR trial conducted by Gorgojo-Martinez et al. shown that both orlistat and liraglutide considerably reduced weight, fasting glucose level, systolic blood pressure, LDL cholesterol, and alanine transaminase. The weight loss was 3.3 kg with orlistat and 7.7 kg with liraglutide, respectively. Compared to 64.7% of liraglutide individuals, 27.4% of orlistat participants dropped 5% or more of their baseline weight. According to Grabarczyk’s research, patients who took orlistat for 20 weeks saw a 2.1% weight loss compared to baseline, those who took phentermine-topiramate for 4.1%, and those who took phentermine for 3.6%. In comparison, patients who participated in MOVE!, the weight management program offered by the Veterans Administration (VA), which required at least three clinic visits, saw a slimmer patient.
Orlistat molecules at BOC Sciences
Phentermine-Topiramate: Phentermine is a sympathomimetic agent that curtails appetite by elevating norepinephrine levels in the central nervous system. Topiramate, a gamma-aminobutyric acid (GABA) receptor agonist, suppresses hunger and enhances fullness. It is frequently utilized for the management of epilepsy and migraine headaches. The FDA has authorized the combination of phentermine and topiramate for obesity control. Substantial weight reduction linked to phentermine-topiramate vs to placebo. A 5% weight reduction was seen in 75% of persons administered phentermine-topiramate compared to 23% of those getting a placebo (OR 9.22, 95% CrI 6.63-12.85, SUCRA 0.95) and 44% of individuals taking orlistat (OR 2.70, 95% CrI 2.34-3.09, SUCRA 0.22). After one year, the excess weight reduction relative to placebo was 8.8 kg (95% CrI -10.20 to -7.42 kg), whereas with orlistat, it was 2.6 kg compared to placebo (95% CrI -3.04 to -2.16 kg).
Topiramate molecules at BOC Sciences
| Name | CAS | Category |
| Topiramate | 97240-79-4 | Impurities |
| Topiramate D-galactopyranose | Carbohydrates, Nucleosides & Nucleotides | |
| Topiramate Dimer Impurity | Impurities | |
| Topiramate impurity B | Carbohydrates, Nucleosides & Nucleotides | |
| N-Methyl Topiramate-d3 | Stable Isotope Labelled Compounds | |
| Topiramate Azidosulfate | 106881-35-0 | Impurities |
| Topiramate Desacetal Impurity (4,5-diol-Topiramate) | 106881-41-8 | Impurities |
| Topiramate Didesacetal Impurity | 106881-42-9 | Impurities |
| Topiramate-[13C6] | 1217455-55-4 | Stable Isotope Labelled Compounds |
| Topiramate-[d12] | 1279037-95-4 | Stable Isotope Labelled Compounds |
| R-Hydroxy topiramate | 198215-60-0 | Carbohydrates, Nucleosides & Nucleotides |
| S-Hydroxy topiramate | 198215-62-2 | Impurities |
| Topiramate Related Compound A | 20880-92-6 | Impurities |
| 2,3-Desisopropylidene Topiramate | 851957-35-2 | Impurities |
| Topiramate EP Impurity D | 950603-46-0 | Impurities |
| Topiramate N-Methyl Impurity | 97240-80-7 | Impurities |
| 1,2:4,5-di-O-Isopropylidene-beta-D-fructopyranose | 25018-67-1 | Impurities |
Naltrexone/Bupropion: Naltrexone functions as an opiate antagonist, whilst bupropion serves as a mild inhibitor of dopamine and noradrenaline reuptake. It has received approval from both the FDA and EMA for the treatment of obesity. These medications together induce satiety by promoting the production of melanocyte-stimulating hormone (MSH) from hypothalamic pro-opiomelanocortin (POMC) cells, resulting in decreased food consumption and higher energy expenditure. Naltrexone/bupropion, similar to other obesity pharmacotherapies, is advised for those with a BMI of ≥30 kg/m2 or ≥27 kg/m2 when accompanied by additional obesity-related comorbidities. An extra yearly reduction of 4.8% in total body weight (average 4.4 kg) has been seen, accompanied by side symptoms such as nausea, headache, and dizziness.
Bupropion molecules at BOC Sciences
Liraglutide: Liraglutide is a glucagon-like peptide-1 (GLP-1) agonist, initially developed for the management of type 2 diabetes (T2D). Administered as a daily injection at a dosage of 3.0 mg, in contrast to a maximum of 1.8 mg daily for the treatment of T2D. Liraglutide facilitates weight reduction by augmenting satiety by hypothalamic activation and prolonging gastric emptying, thus reducing food consumption. It is sanctioned by the FDA and EMA to facilitate weight reduction in individuals with a BMI of ≥30 kg/m2 or ≥27 kg/m2 with obesity-related comorbidities. Prevalent adverse effects encompass nausea, vomiting, and pancreatitis. A supplementary yearly weight reduction of 5.3-5.9 kg has been noted in comparison to placebo.
Semaglutide: Semaglutide is the latest GLP-1 analogue authorized for Type 2 Diabetes (T2D) and is presently administered via subcutaneous injection at a maximum dosage of 1.0 mg once weekly for T2D therapy. It is authorized for use as monotherapy for individuals who cannot tolerate metformin or as an adjunct therapy. The total weight reduction linked to semaglutide administration is up to 4.6 kg and 6.5 kg at dosages of 0.5 mg and 1.0 mg, respectively, during a duration of 40 weeks. Comparative investigations have indicated that semaglutide 1.0 mg had superior weight reduction effectiveness compared to dulaglutide 1.5 mg (6.5 kg versus 3.0 kg). A phase II dose-finding experiment revealed more significant reductions in body weight with daily subcutaneous semaglutide at doses beyond 0.2 mg compared to daily liraglutide at 3.0 mg. The advancement of oral semaglutide for type 2 diabetes and/or obesity is noteworthy, as alternative GLP-1 analogues are now accessible just as injectables, sometimes constraining their application. A recent experiment indicated that oral semaglutide (14 mg once day) produced superior weight reduction compared to subcutaneous liraglutide (4.4 kg vs. 3.1 kg) over a period of 26 weeks.
Semaglutide molecules at BOC Sciences
References
- Idrees Z., et al., FDA-approved pharmacotherapy for weight loss over the last decade, Cureus, 2022, 14(9).
- Williams D M., et al., Drug therapy in obesity: a review of current and emerging treatments, Diabetes Therapy, 2020, 11(6): 1199-1216.
- Tak Y J., et al., Anti-obesity drugs: long-term efficacy and safety: an updated review, The world journal of men’s health, 2021, 39(2): 208.