Comparing the effectiveness of weight loss drugs
A recent analysis has compared the effectiveness of the 5 weight-loss drugs that have been approved by the USA’s FDA. These drugs are: orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide. The drugs were compared against a placebo, and not against each other. The authors of this study conducted a systematic review with a meta-analysis that included 28 randomised clinical trials, which related to 29,018 patients. They also looked at the incidence of adverse events whilst patients were on these drugs.
Each drug was associated with achieving at least 5% weight-loss at 52 weeks, with phentermine-topiramate and liraglutide having the highest odds of achieving 5% weight loss. The authors highlighted that more work is necessary to discover the long-term effects of pharmacotherapy for obesity, as concerns over their safety still exist amongst clinicians. The authors go on to explain how there are no recommendations for clinicians when it comes to choosing individual drugs for patients and with differences in safety, efficacy and response to therapy, the ideal approach to weight-loss should be highly individualised, identifying appropriate candidates for pharmacotherapy, behavioural interventions and surgery.
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Does nanoparticle drug delivery offer hope to obese patients?
Researchers at MIT and Brigham and Women’s Hospital have developed nanoparticles to deliver anti-obesity drugs. In a study using a mouse model, researchers were able to effectively deliver drugs which converted white adipose tissue into brown adipose tissue – thereby helping to burn off the fat. The drugs also increased vasculature to these areas, allowing for more drugs to be subsequently delivered to the correct areas, helping to avoid unwanted side effects in other parts of the body.
The researchers are particularly encouraged to know that they can deliver the drug to particular areas and have an overall positive effect. After treating the mice intravenously, it was noted that those on a high-fat diet lost approximately 10% of their body weight, with cholesterol and triglyceride levels also dropping. Furthermore, the treatment did not cause any side effects to the mice. Further research involves looking into an easier delivery approach of the nanoparticles, such as delivering them by mouth – something that has proven difficult in the past. Overall, the authors are reassured by their results and are looking forward to taking the research further.
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Fatty liver disease reversed by pill in mice
In the search for a pill to combat obesity and its associated co-morbidities, researchers have found a bile acid that is capable of preventing and treating fatty liver disease in mice. In a recent study obese and diabetic mice were fed glycine-beta muricholic acid (Gly-MCA) pills. Even with a high fat diet these mice were less fat and had less insulin resistance than the control group who weren’t given Gly-MCA.
Gly-MCA is a bile acid that can inhibit the farnesoid X receptor (FXR) which maintains metabolism by sensing and regulating bile acids, fats and glucose in the body. The receptor itself plays a complex role in the pathogenesis of metabolic dysfunction in the body and that may be why Gly-MCA had such a large effect on the obesity of the mice. Usually, bacteria break down the bile acids that inhibit FXR, however these researchers found a bacteria resistant acid, Gly-MCA, that also inhibits FXR, allowing them to conduct the study. The drug itself can be consumed in pill form for humans and provides a possible avenue for the treatment of obesity, as well as fatty liver disease. However until now there has been little research into its usage, particularly with regard to toxicity. In the mice, there were no signs of systemic, hepatic or intestinal toxicity, but more work remains to be done in order to fully explore the effects of this drug in animal models and humans.
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Antibiotics encourage obesity
Continued use of antibiotics in children can lead to obesity, changes in bone growth and altered gut bacteria, according to a new study in Nature Communications. The team stated that, in the USA, 262 million courses of antibiotics were prescribed to outpatients, that’s 842 per 1000 people a year, with use at its highest in children under 10. Estimates suggest children may have had 10 courses by this age. Antibiotics are well known to impact on microbial function, but little study has been done into how they affect host health during critical developmental stages.
The researchers mimicked childhood antibiotic use by using mice as their models. They found that early life pulsed antibiotic treatment (PAT) leads to short term increases in mouse weight and bone growth, whilst also leading to long-term changes in composition of gut bacteria. These changes included altering the species of the bacteria present and therefore the metabolic functions as well. Furthermore, they found that the bacteria in the antibiotic treated mice took much longer to adapt to new diets than those without antibiotics. The team remain cautious regarding the implication for humans though.
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Liraglutide, a new drug for weight management
Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon like peptide-1 analogue that is used in pill form to treat diabetes, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. There has been concurrent reductions in glycaemic variables and multiple cardiometabolic risk factors, as well as improvements in health-related quality of life.
The 56-week study was a double-blind trial involving 3731 patients with a BMI above 30 that did not have type 2 diabetes. Patients were randomly assigned in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients). Both groups received counselling on lifestyle modification.
63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight, and 33.1% and 10.6%, respectively, lost more than 10% of their body weight. This illustrates the effectiveness in losing weight from this recently marketed drug, which has been approved by the European Medicines Agency but is yet to be licensed in the UK, where still the only available drug is orlistat.
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