Weight Loss Breakthrough
This health information is in no way meant to provide you with medical advice. Please consult a health care provider, in person, for medical advice tailored to your specific needs.
Obesity has been described as both a global epidemic and even a pandemic. Nearly 15% of the world’s population are said to be obese with a body mass index (BMI) ≥ 30 kg/m2. Over 40% of are overweight (BMI ≥ 27 kg/m2) and it’s estimated that by 2030, around 60% of the world’s population will be overweight or obese. https://academic.oup.com/endo/article/161/3/bqaa024/5739626
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155232/
Obesity and suboptimal metabolic health significantly increase a person’s risk of developing type 2 diabetes mellitus (T2DM), cardiovascular disease, neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, cancer and non-alcoholic fatty liver disease (NAFLD). Obesity and impaired metabolic health have also emerged as important determinants in severe coronavirus disease 2019 (COVID-19). https://www.nature.com/articles/s41574-020-00462-1
Social stigma and discrimination toward people living with obesity have been shown to adversely affect psychological and physical health, leading to a lower quality-of life and higher rates of depression. Given that even modest weight loss (5%-10% of total body weight) significantly improves health and wellbeing in people with obesity, effective weight loss strategies have become a major focus in public health policy.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155232/
So what causes overweight and obesity?
The prevailing medical hypothesis and one I was taught in medical school thirty years ago, is that obesity is caused by a simple imbalance between energy in, (excessive calorie intake) and energy out, (insufficient energy expenditure). However, recent studies have demonstrated significant weight increases across populations over time, even with the same amount of caloric intake and energy expenditure. Researchers now agree that the cause of overweight and obesity is multi-faceted. Contributing factors include the quality of carbohydrate calories consumed (high vs low glycemic load), genetic factors and multiple environmental factors. These include exposure to an adverse environment in the womb during fetal development (maternal starvation, smoking, high BMI, gestational diabetes); the composition of our gut microbiome; disrupted circadian rhythms (e.g. in shift workers); psychological distress / stress and endocrine disrupting chemicals, (e.g. in plastics) to name a few. https://academic.oup.com/endo/article/161/3/bqaa024/5739626
Within the body, energy balance is made up of a highly complex system, with interactions between nutritional signals, endocrine hormones, messaging within the nervous system and key areas in the brain (e.g. the hypothalamus). Obesity has been linked to break-downs and dysregulation within this complicated system.
One of the endocrine hormones that plays a key role in energy balance is glucagon-like peptide 1 (GLP-1), an incretin hormone that’s primarily synthesized in the small intestine when we eat. GLP-1 decreases appetite, slows stomach emptying, increases glucose-stimulated insulin secretion (needed to transport glucose for energy into cells) and results in a negative energy balance.
Why doesn’t dieting and exercising cause weight loss in everyone?
It seems that weight gain induces a vicious cycle for many people — It seems to get harder and harder to lose weight, the more weight that they gain. This vicious cycle may, in part, be explained by the finding that weight gain seems to cause abnormal GLP-1 signalling that actually prevents weight loss and promotes further weight gain.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155232/
The breakthrough!
The first injectable GLP-1 agonist therapy, Xenatide (Byetta), was approved by the American Food and Drug Administration (FDA) for the treatment of type 2 diabetes mellitus (T2DM) in 2005. Xenatide’s ability to induce weight loss in people with T2DM led to specific weight loss trials and in 2014, the FDA approved another injectable GLP-1 agonist, liraglutide (Saxenda), for the treatment of obesity.
Several other injectable GLP-1 agonist therapies have since been developed and approved, with the latest, Semaglutide (Ozempic), generating a great deal of excitement. Dr. Wilding and the Step 1 Study Group recently showed that semaglutide plus lifestyle intervention results in significant and sustained weight loss. Those taking semaglutide had a mean reduction in body weight of around 15% over 17 months, while over a third lost more than 20% of their body weight. Nearly 90% of participants achieved at least a 5% reduction in total body weight. This weight loss also translated into an improvement in metabolic status / cardiometabolic risk / pre-diabetes / diabetes and physical ability / functional status.
https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
As with any medication, there are side effects — the most common being nausea, diarrhea, vomiting, and constipation. Less common side effects include gallbladder disorders and pancreatitis. Blood glucose and blood pressure monitoring may also be recommended as some people can experience low blood glucose levels and low blood pressue. People with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome 2 (MEN2) are advised to consult with their specialist care team before using GLP-1 agonists.
I’ve now been prescribing GLP-1 agonist therapies since 2013 (when Xenatide was first approved for people with T2DM in Australia). In 31 years of medical education and more than a decade as a practising endocrinologist, this is the first really effective metabolic therapy that I’ve prescribed. As with all weight loss interventions, it works best when used as one aspect of a tailored, multidisciplinary approach.
Prior to GLP-1 agonist therapy, there should always be a comprehensive medical assessment; to exclude possible reversible causes of weight gain (e.g. thyroid, adrenal, pituitary disease, auto-immune and other conditions) and to check for high blood pressure / pre-diabetes / diabetes / high cholesterol / cardiovascular disease / other significant medical conditions. Monitoring for side effects and response to treatment / ongoing dose titration is also required.
Long term lifestyle changes often require the help of a dietician, specialist nurse practitioner, exercise physiologist, physiotherapist, psychologist, counsellor, lifestyle coach and for many, complementary therapists.
As amazing as GLP-1 agonist therapies are, lifestyle change is still at the forefront of health and wellness. The best news is that the GLP-1 agonists seem to make lifestyle change so much easier by decreasing appetite and increasing wellbeing.
And for those people with needle phobia or for whom injectable therapy is off-putting, there will soon be oral GLP-1 preparations, with semaglutide (Ozempic) likely to be the first.
Although the phrase ‘weight loss’ is still the terminology our society likes to focus on, the real issue here is optimal metabolic health and wellness; not numbers on a weighing scale or clothing size.
GLP-1 agonist therapy is absolutely changing lives — improving physical, metabolic, mental and emotional health.
The next step is to make GLP-1 agonist therapies more affordable and more widely accessible….
