Kelly Lisciandro, DO 585-364-0025
From the Expert
To Inject or not to inject? That is the question.
Written by Dr. Kelly A. Lisciandro, DO
The hype in the weight loss industry is the GLP-1 RA (glucagon like peptide-1 receptor agonists). These are the prescription medications which have been all over the media promising and promoting weight loss.
What is a GLP-1 agonist? What does it do? Why does it cause weight loss? What are the risks associated with this weekly injectable drug for weight loss? I plan to simplify it from a clinical standpoint.
The mechanism of action and pharmacokinetics of any drug is how the drug works in the body, its onset, activity, and excretion. We have natural hormones in our bodies that are released in response to what we do to our bodies. For instance, we eat a carbohydrate load, our body will secrete insulin. This occurs with digestion and absorption of glucose from the GI tract and release of insulin into the blood stream by the pancreas. We give our body carbohydrate and volume, and our brain secretes glucagon like peptide. Think about the brain as an endocrine organ, just like the pancreas. We secrete hormones from it. Our whole endocrine system in the body is controlled by the hypothalamic-pituitary-adrenal axis. The hypothalamus and pituitary glands are in our brains. These are the endocrine organs of our brains. They control all our hormone release in our bodies in response to triggers.
The drug industry synthesizes drugs that mimic what we already do in our bodies, our natural hormonal state. These drugs are longer acting, and time released so the short-lived effect in our brains now will be faster and longer with the drug. Semaglutide is a synthetic (created in a lab) long-acting form of GLP-1 that is a weekly injectable drug. The benefit of long acting GLP-1 is that we feel fuller faster and longer in response to food intake. That leads to early satiety and less hunger. We eat less and we don’t feel hungry for hours. Clinically, what I have seen and heard is that patients on Semaglutide must force themselves to eat and are never hungry.
When we eat, our GI tract stretches by food and our glucose levels increase. Our brains will release GLP-1 in response but it is short lived, and we don’t feel full very long and get hungry easily. We have all experienced this. We eat regularly because we get hungry and are not satisfied by what we ate an hour earlier. I call this “hyperappetitemia”, the driving force of obesity. That is not a medical term, but I like it because it describes so many of obese Americans. We are hungry all the time. We are not balanced hormonally, neurologically, or metabolically.
The GLP-1 receptor agonist will increase glucose dependent insulin secretion with a carbohydrate load, decrease inappropriate glucagon secretion, slow gastric emptying and acts on the part of the brain that regulates appetite and caloric intake. These new medications are designed to address the hormonal aspect of weight management. Weight is not just metabolic; it is hormonal and metabolic. That is why these drugs are so effective for weight loss.
The problem with big pharma is that these drugs are not covered by most insurance plans and are extremely expensive. No one can afford them. I am talking in the range of $800-1000/month or maybe with a coupon $550/month. The cost is astronomical which makes effective prescription weight loss only cosmetic and for the wealthy. These drugs have been shown to decrease weight and maintain weight loss over time in adults and adolescents over the age of 12. They have been shown to decrease repeat heart attacks in obese patients with heart disease without diabetes. They can be used to help cardiovascular disease and weight. Heart disease is the lead killer in the US today. We have drugs that can be used in heart attack survivors for secondary prevention of another heart attack and weight loss. Everyone should have access to these drugs in the patient centered model of disease prevention and even treatment.
The drugs are not the whole answer though. They must be combined with lifestyle changes. That means one must make some changes in their diet. A diet high in vegetables, lean protein with low good carbohydrates and low good fats. Or a plant-based diet that is high in fiber. The American diet is killing us and is unhealthy. We must strive for healthier habits to be healthier and prevent disease. Studies show up to 17% weight reduction in patients that take GLP-1 with lifestyle changes as opposed to 7% with drug alone.
Now, this is a good thing in many ways but it can work against one’s body also. What happens when a person stops eating and drinking fluids? What happens when a patient can’t learn to eat when not hungry? There are risks to every drug and everything we do to our bodies.
I had a patient that didn’t eat or drink for 3 weeks. By the time she saw me, her kidneys had shut down and she was on the verge of hypovolemic shock. I learned of the new medication, a GLP-1 RA, when she came to see me for extreme fatigue and weakness. She was so sick. She thought it was okay because she was supposed to be losing weight on the medication. She was diabetic so had both me as her PCP and an endocrinologist managing her diabetes. She had lost about 40 lbs since starting the medication. This was not the right way to lose weight and the drug almost killed her. She is thankfully still alive with a prolonged hospitalization to manage the ill effects of the drug. The drug is contraindicated in her now.
There are contraindications for all drugs. For the GLP-1 receptor agonists, a history of pancreatitis or a family history of medullary thyroid cancer are absolute contraindications. I have had to stop the medication in 2 patients for pancreatitis and 1 with ileus meaning the GI tract stopped moving. If an ileus becomes gastroparesis this is an irreversible adverse reaction.
When considering injectable drugs for weight loss, you must decide if the drug is right for the patient, do they meet criteria for treatment and what is the risk vs. benefit of the drug. To inject or not to inject is not just the choice of the patient, it is also the choice of the physician. We individualize the decision to prescribe with every single patient. To sign or not to sign, that is the question.
Mastering Primary Care and Medication Management
Written by Dr. Kelly A. Lisciandro, DO
When I first considered online teaching as a side gig to practice in primary care, my first thought was, “what am I good at? What can I teach the public or young physicians, residents, physicians assistants and nurse practitioners?” My a-ha moment was medication management. As primary care physicians, we do become experts. We become experts at this. What is the value of that expertise for our patients?
We take so many considerations into account when prescribing medications. First, cost. I don't want to break the bank for my patients. I understand the pharmaceutic world in this country and the burden it places on patients just to get or obtain treatment for an ailment or a disease. Cost effective medication management is crucial in primary care. Think about it, would you stay on a medication that costs you $500 a month? That happened to me as a patient. I needed the medication, but it was $496 on my high deductible plan. It was an asthma medication. I needed it to breathe. I refused to pay it. Instead, I sought out a foreign pharmacy online to get a three-month supply. I got the equivalent drug for $136 with shipping fees!
We must take cost into consideration as the number one factor. Our goal is for compliance with medication management. If I don't advocate for my patients then who will? We, as primary care physicians, become experts at it.
The second issue is risk versus benefit for that patient and the treatment necessary. We become experts at knowing our patients and knowing the potential risks associated with every single medication we prescribe. For example, a patient wants Naltrexone because she heard it can help with weight loss and “inflammation” in her body. Inflammation has become a buzzword in medicine these days. The requested “CRP” lab test because “I need to know how much inflammation I have in my body”. And if it comes back elevated, what do we do as clinicians? Nothing.
Back to Naltrexone. Do you know the risk associated with Naltrexone? It has serious mental health contraindications such as suicidality, psychosis, and mania. Now, I don't know about you, but these are absolutely devastating and potentially fatal adverse reactions to a medication. I don't prescribe Naltrexone. I don't prescribe it because of these risks. Weight loss and unnecessary treatment of subjective “inflammation” would not warrant such great risk of a medication with no real benefit for the condition. What I recommend for both weight loss and inflammation is diet and exercise. There's great information out there on the web for anti-inflammatory foods. There is an excessive amount of information out there on diet, exercise, and weight loss. All come without the serious side effects of psychosis, suicidality, or mania.
Mental health issues are rampant in primary care currently considering the aftermath of a global viral pandemic. There is very little care available out there for psychotherapy and/or psychiatry. We must take into consideration every single potential side effect of a medication before prescribing it. First, do no harm. That is the oath we all took.
Every drug must have risk versus benefit profile. Do the risks of the drug outweigh the benefit of the drug in this patient? We become experts at this. We are not perfect and there will always be mistakes but not without the utmost of consideration prior to signing that prescription.
That leads to the third consideration in medication management. If you prescribe medication to a patient who already is prone to that side effect, do you think that patient will take the medication or remain on it? Especially if that medication makes their quality of life worse than what it was prior to that 15-minute office visit. Absolutely not.
For example, would you put a patient with chronic bronchitis with a persistent cough on an ACE inhibitor? Absolutely not. Because a dry cough is the most common reason to stop an ACE inhibitor. Or would you put a patient riddled with the pain of fibromyalgia on a statin? That would be a hard sell. The most common side effect to the statins is body aches.
We do become experts. Jack of all trades, master at none. I disagree. Primary care physicians are masters. We master patient care.
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