Efficacy and safety of semaglutide for weight loss in patients with obesity
In this paper, published in The Lancet, the authors sought to assess efficacy and safety of the glucagon-like peptide-1 (GLP-1) analogue semaglutide, in comparison with a similar drug liraglutide, and placebo. The study was done in 8 countries, involving 71 clinical sites, with the primary endpoint being weight loss at week 52.
GLP-1 analogues mimic the function of human GLP-1, which regulates insulin secretion and glucagon secretion. These processes are linked with appetite, satiety and energy intake. This study found that these drugs, which were initially licensed for diabetes treatment, resulted in weight reductions which were significantly greater than the placebo group at 52 weeks. This weight loss is primarily due to the individuals consuming less energy, because of a combination of appetite suppression and enhanced satiety. Semaglutide was found to be the most effective, with weight loss of 11-14%, compared to Liraglutide’s 7-8%. In terms of side-effects, the most common complaint was of nausea. This was found to be dose dependent, so higher doses made side-effects more likely. Overall however, semaglutide was well tolerated, with no unanticipated safety or tolerability outcomes. Semaglutide has been shown to have a good benefit-risk profile which further supports its use as a weight management drug in its own right, instead of just being licensed for diabetes. Phase-3 studies are ongoing.
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Selective enzyme inhibitor reveals a novel role in fat metabolism
Cellular metabolism is a chain reaction of steps, controlled and aided by enzymes, which leads to the production of molecules that the cell requires. An important family of metabolites, called ceramides, are known to have an important role in cell signalling and apoptosis, as well as other physiological functions
In this study published in Nature, the researchers tested a new selective enzyme inhibitor called CerS1 on mice being fed a variety of different diets. They discovered that it has an important role in fat metabolism, specifically on fat deposition in mice. When they used the enzyme to inhibit metabolism, they significantly lowered fat deposition in mice, even if they were on a high-fat diet. They also found that it did not impact on glucose disposal nor insulin stimulated glucose uptake.
Although a lot more research is needed to go from mice studies to human trials, by directly affecting the cellular metabolism to prevent fat deposition, this research has demonstrated a potentially exciting new therapeutic avenue for treating obesity.
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Does environment influence childhood BMI? A study of children aged 3–11
Obesity is simply caused by an imbalance in energy consumed and calories burned, however what causes this imbalance is complex and multifactorial. If enough calories are burned through physical activity, then an individual should not gain weight. Following this rationale, if an environment is more conducive to exercise then an individual is less likely to be overweight. This argument is the basis of this paper, which explores the relationship between environment and children’s BMI.
The study included 6001 children in England, between the ages of 3 and 11. The environmental measures used looked at levels of green space, gardens, crime or multiple deprivation of a neighbourhood. Crime rates were derived from police force data, on four criminal offences; burglary, theft, criminal damage and violence. The study found that there was a moderate relationship between environment and a child’s BMI, however it is unlikely that this relationship was causal. The results instead suggest that environmental variables, such as amount of parks or recreational facilities, may be driven by selection. So those families that are less likely to have overweight children, are more likely to choose to live in greener areas. This research goes against many previous studies which suggests a strong causal link between exercise promoting environments and obesity. In light of this, future research and health policy should consider the assumption that these two are linked and that managing the environment will invariably lead to lower levels of obesity.
Read MoreCardiovascular Safety of Lorcaserin in Overweight or Obese Patients
In some patients, weight-loss guidelines recommend the use of pharmacological agents as adjuncts to lifestyle modification. Although not many are licensed, they have been shown to be effective for long-term weight management. One of the serious downsides of these drugs is the side-effects. Depending on their sight of action, they have been known to precipitate severe complications in the cardiovascular or neuropsychiatric systems, leading to their removal by regulatory agencies over safety concerns.
Lorcaserin is a selective serotonin 2c receptor agonist that modulates appetite. It has proven efficacy for weight management in overweight or obese patients. This paper published in the New England Journal of Medicine sought to determine the cardiovascular risk associated with its use as an obesity treatment. From the study of 12,000 patients, it found no increased risk of cardiovascular complications. It also found that alongside significant weight loss there were also reductions in triglyceride levels and in dysglycaemia. In addition, it was found that there was an improvement in heart rate and blood pressure, which is in contrast to most other weight loss agents. Overall, this drug is an effective adjunct to lifestyle interventions in patients with obesity and cardiovascular disease, and doesn’t increase the risk of cardiovascular events.
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Obesity and loss of disease-free years owing to major non-communicable diseases
Obesity is known to be associated with an increased risk of several major non-communicable diseases including type-2 diabetes, coronary heart disease, stroke, asthma and several cancers. It was previously thought that metabolically healthy obese (MHO) individuals were at no increased risk of these conditions. MHO is characterised by a healthy blood pressure, low cholesterol, normal insulin regulation and reasonable levels of physical fitness. However, more recent longitudinal studies have found that these individuals show a strong tendency to progress to an unhealthy obese state. What has been relatively understudied is the degree to which obesity is associated with the development of these major non-communicable conditions.
In this large study, published in The Lancet, the health data from 120,181 participants was analysed in order to determine how many disease-free years were lost to obesity. The participants were of a range of BMIs, but free of other comorbidities. They found that overweight patients lost 1 disease free-year, mildly obese patients 3-4 years and the severely obese 7-8 years compared with normal weight participants. Severe obesity was associated with the loss of 7-10 disease-free years in active and inactive individuals; current, past and never-smokers; and those of high and low socioeconomic position. The paper suggests that obesity, even in those with a healthy metabolic profile, leads to a substantial loss of disease-free years, across the social hierarchy and irrespective of lifestyle factors such as physical activity and smoking.
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