This article was originally written for emeranmayer.com
For those struggling to lose weight, it can seem like a daunting and, at times, insurmountable challenge. We have heard the phrase “eat less and move more” repeated countless times by experts and officials, and yet clearly something more is needed. Nearly half of all adults in the United States reported attempting to lose weight in the last 12 months between 2013 and 2016, most commonly with those exact methods: eating less and exercising more. As traditional interventions and public health measures have failed to stem the growing tide of obesity, a demand for new weight loss methods has increased.
This is where Ozempic, a new weight loss drug touted by celebrities and plastered across social media has come into the picture. It promises steady weight loss without having to focus on eating less or exercising more, and the results are seemingly encouraging, but as with all drugs, there may be downsides to its long-term use.
Obesity is a serious and increasingly common disease impacting a startlingly large population of Americans. It is estimated that about 42 percent of the US population is obese and 1 in 3 US adults is overweight. As discussed many times in this newsletter, this puts close to a half of the population at a greater risk for developing a variety of diseases including heart disease, stroke, type-2 diabetes, early cognitive decline and even certain types of cancer.
“The medication requires a prescription written by a doctor and is then typically self-administered weekly, although it is not currently approved for weight management specifically.”
Ozempic, the brand name for semaglutide, a class of Glucagon-like peptide-1 (GLP-1) agonists, is an injectable antidiabetic medication used for the treatment of type-2 diabetes as well as an anti-obesity medication for long term weight management. The medication requires a prescription written by a doctor and is then typically self-administered weekly, although it is not currently approved by the FDA for weight management specifically.
As a GLP-1 receptor agonist, Ozempic essentially boosts the effects of the body’s naturally occurring GLP-1, a natural peptide hormone that is stored in special cells in the small intestine, so called enteroendocrine cells, and released from them after consumption of a meal. Gut microbial metabolites such as short chain fatty acids and secondary bile acids play a major role in stimulating the release of this satiety hormone from the enteroendocrine cells, and have been implicated in the pathophysiology of overeating and food addiction. The release of GLP-1 has effects both on the gut, the pancreas, and the brain. In the pancreas it stimulates insulin secretion and inhibits glucagon secretion and in the gut it slows gastric emptying. In effect, this hormone can lower blood sugar levels and slow the rate of stomach emptying, and prolong the feeling of fullness after a meal. In the brain, GLP-1 receptor agonist have been found to act on regions involved in the regulation of food intake such as the hypothalamus and reward regions, and this central effect is thought to mediate satiety and weight effects in humans. GLP-1 can influence the brain directly by traveling through the blood stream or indirectly by stimulating vagal nerve fibers that reach the brain. Essentially, taking Ozempic can regulate appetite, satiety and food intake without conscious effort, leading to a reduction in caloric intake and subsequent weight loss.
“Since it is not yet approved specifically for weight management, research has not yet been done on the potential more serious, long term side effects of taking this weekly injection.”
As is typical of any drug, prescription or not, minor side effects may occur, most commonly irritation at the injection site as well as digestive issues such as nausea, vomiting, diarrhea, or constipation. Similar symptoms can occur in gastroparesis a condition in which gastric emptying is delayed, and which is characterized by uncomfortable feelings of fullness, nausea and vomiting. It is unclear which role the drug’s effect on gastric emptying and on brain regions regulating satiety plays in the development of intolerable side effects of nausea and vomiting plays. Since Ozempic it is not yet approved specifically for weight management, research has not yet been done on the potential more serious, long term side effects of taking this weekly injection.
“Administering a drug that causes an unnatural level of stimulation in regard to feeding and digestion, may likely have an indirect impact on the gut microbiome.”
In the case of gastroparesis it is well acknowledged that the disorder stems from a disruption of the bidirectional communication in the brain-gut-microbiome system. The interactions between the microbes living in our gut, and the metabolites they generate from our diet with the hormones stored in the intestinal enteroendocrine cells of the gut play a crucial role in gastrointestinal motility and of satiety mechanisms in the brain. As Ozempic impacts the brain-gut-microbiome system directly by “influencing brain regions involved in the regulation of feeding” dysregulation of this system by chronic stimulation of brain satiety mechanism may likely have an indirect impact on the gut microbiome.
Additionally, the medication “tricks” the body into thinking it is not hungry in order to minimize caloric intake. It is possible for intake to drop too far and too quickly for the body’s energy needs and for proper healthy functioning. Many users have reported heart palpitations and a drastically increased heart rate as a result, putting excess strain on the body. Undereating has also been shown to disrupt the gut microbiome and alter the balance of beneficial microbes. A large number of individuals who have struggled with an eating disorder at some point suffer from gastrointestinal dysfunction, typically either from chronic undereating or vomiting after meals, both of which can be caused by long term usage of Ozempic.
“Once an individual stops taking Ozempic, they will likely gain the weight back, sometimes more than they originally lost, unless further diet and lifestyle changes take place, creating a dependency for medical intervention.”
Undereating can also lead to a lower metabolic rate in the long term as the body learns to adapt to this lower caloric threshold. In short, the body burns fewer calories at rest to compensate for the fewer calories coming in. This can lead to metabolic dysfunction down the line, especially if use of Ozempic is discontinued. Once an individual stops taking Ozempic, they will likely gain the weight back, sometimes more than they originally lost, a phenomenon referred to as the “Yoyo effect”, unless further diet and lifestyle changes are implemented, creating a dependency for medical intervention.
While these “miracle” drugs may seem like the best and easiest option for weight loss, there is much to consider before embarking on such treatment. There is irrefutable evidence for long term, sustainable weight loss, however weight loss occurs only when actively using the medication and may impart numerous side effects, many of which are still unknown. Although the discussion around weight loss is complicated, much is needed to be done to improve the public’s education on a healthy diet and lifestyle interventions as well as make healthier options more accessible and affordable to people in lower socioeconomic sections of the population who suffer disproportionately from the negative health effects of obesity, and may not be able to afford expensive pharmaceutical interventions.