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The Ramifications of Obesity on the Physiology and Medication Utilization

January 1 gives us an opportunity for self-assessment and evaluation of our physical, spiritual, and emotional lives. I am continually asking myself how to be a better person, husband, dad, pharmacist, pilot, and flight instructor than I was before. 

I enjoy digesting surveys on the most popular New Year’s resolutions each year. In a Statista study of 1,500 Americans, the second most common New Year’s resolution was losing weight. Almost 50% of the respondents wanted to lose weight.

The body mass index (BMI) is the standard measurement used to classify if a person is overweight. A BMI between 18.5 and 24.9 is average, 25 to 29.9 is overweight, 30 to 34.9 obese, 35 to 39.9 morbid obese, and greater than 40 is super obese. Based on 2018 data from the Center for Disease Control (CDC), the obesity prevalence was 40.0% among adults aged 20 to 39 years, 44.8% among adults aged 40 to 59 years, and 42.8% among adults aged 60 and older.

The comorbidities of obesity increase each year in the U.S. Obesity may cause obstructive sleep apnea (OSA), endometrial, colon, prostate and pancreatic cancer, depression, hypertension, stroke, coronary heart disease, surgical risk, diabetes type 2, and dyslipidemia (high cholesterol). Many of these disease states have an increased risk of mortality. A majority of the acute coronary syndromes (heart attacks) I saw as a cardiology pharmacist were obese patients with BMIs over 30.

Obesity causes an increase in adipokines in the body. Adipokines are cell signaling molecules produced in adipose tissue that cause an increase in inflammation and thrombosis (clots). Obesity increases the risk of developing atrial fibrillation by 50%. Atrial fibrillation increases the risk of stroke by five times versus a patient without atrial fibrillation.

The significant contributors to our obesity crisis are diet, inactivity, and social behavior. In the past decades, obesity has been commonly seen as being lazy and weak by their friends, leading to social stigmatization. Medical schools, nursing schools, and physician assistant programs have added nutrition education as part of their curriculum.

The physicians’ big question is, do I need to increase the dose of the medication due to the patient’s weight? The answer to this question is “sometimes.” The increase in drug dose leads to an increased risk of side effects and complications. Many medications are dosed by weight. Antibiotic therapy, especially in children and adolescents, is weight-based dosing. With the increasing rate of child obesity, this becomes a challenge. Children who are obese may receive adult doses, which increases the risk of side effects.

As I mentioned above, there is an increased risk of the obese patient manifesting atrial fibrillation. The mainstay medication to prevent a stroke in atrial fibrillation is warfarin therapy. Warfarin is an anticoagulant with some significant adverse effects of severe GI bleeding and intracranial hemorrhage. It takes higher doses and a longer timeline for warfarin to reach a therapeutic level in obese patients. The patient needs to be bridged with low molecular weight heparin (enoxaparin) until the warfarin comes to a therapeutic level. The double whammy is that enoxaparin is a milligram per kilogram dose given twice a day. The patient now needs two anticoagulants to prevent stroke, and both anticoagulants have a high risk of causing bleeding. The data with the newer anticoagulants, such as apixaban (Eliquis®) or rivaroxaban (Xarelto®), is not robust for dosing obese patients. So, for now, a dosing change with these medications is not indicated.

In the ’90s, amphetamine-like medications were given for weight loss. My experience with weight loss medications started with methamphetamine hydrochloride (Desoxyn®). A few observational, small population studies showed about a half-pound per week weight loss. Once the trial was stopped, the weight came back. The abuse potential was increased the longer the patient was on methamphetamine. Another option was the Fen-Phen combination medication regimen. This weight loss regimen combined fenfluramine and phentermine for weight loss. Fenfluramine was an appetite suppressant, and phentermine has amphetamine-like properties. Thirty percent of the patients prescribed this combination had valvular problems. Upon surgery to replace the dysfunctional valves, the valves had become hard with a pearly appearance. Fenfluramine and dexfenfluramine were taken off the market by the FDA on September 15, 1997.

The current medications that the FDA has approved are orlistat (Xenical®), phentermine/topiramate (Qsymia®), naltrexone/bupropion (Contrave®), liraglutide (Saxenda®), and semaglutide (Wegovy®) for long-term use in weight loss. Liraglutide is FAA approved for diabetes type 2 only. Naltrexone/bupropion and phentermine/topiramate are not FAA approved for weight loss. Orlistat and semaglutide are FAA-approved for weight loss.

Orlistat (Xenical®), 120 mg dose, is a prescription-only medication. This dose prevents 1/3 of dietary fat from being digested. Forty percent of the patients enrolled in the initial Xenical® study, in conjunction with exercise and caloric restrictions, lost 5% or greater initial body weight (package insert Xenical®). Five percent of weight loss is necessary to decrease cardiovascular disease and diabetes. Orlistat (Alli®) is a 60 mg dose, sold over the counter, and prevents ¼ of dietary fat from being digested. Orlistat blocks lipase, an enzyme that breaks down dietary fat to be absorbed in the body. The side effects are pretty benign except for uncontrolled leakage of oily stools. Orlistat is prescribed or used in adults and children over 12 years.

Semaglutide (Wegovy®) is an intramuscular injection approved for weight loss administered once a week. Semaglutide mimics glucagon-like peptide-1, targeting brain areas that regulate food intake and appetite. Before starting semaglutide, the patients must also have high blood pressure, diabetes type 2, or hyperlipidemia. Semaglutide (Ozempic®) is the same medication used in diabetes type 2 to control glucose by increasing insulin production. There are four 68-week randomized controlled trials that studied semaglutide. In the largest trial, patients lost 6.2% of their initial body weight (N Engl J Med 2021; 384:989-1002).

Over-the-counter products, such as Hydroxycut® and Hoodia Gordonii, lack studies showing consistent, safe, and efficacious weight loss. I have multiple stories of young patients coming in with deadly cardiac arrhythmias due to the high amounts of caffeine and guarana (potentized caffeine) in each product. The patients had been at their gym. The combination of high caffeine levels and low potassium caused a very dangerous cardiac arrhythmia.

If weight loss is your resolution for 2022, please contact your healthcare provider for your annual physical, laboratory evaluation, and nutrition consult. Diet, exercise, and behavior modification is your best option to start. Weight loss with medications is the last option to discuss with your healthcare provider. Weight loss, in conjunction with exercise, will decrease your blood pressure, reduce your risk for diabetes and provide an overall feeling of wellbeing. Be well and fly safely.

Larry M. Diamond, PharmD, CFII

Larry Diamond has a Doctor of Pharmacy Degree and has been a pharmacist for 37 years. Larry’s pharmacy practice has been as a Clinical Pharmacy Specialist in Cardiology, Orthopedic Surgery Specialist and most recently Clinical Pharmacy Coordinator. He is a CFII, a pilot for 33 years and has been an AOPA member since 1984.

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