Many prescription drugs can have harmful side effects on some people. However, some have beneficial side effects. For example, millions of young women discovered that oral contraceptives improved and sometimes cured their acne. Statins are another example. They were discovered in a type of soil fungus and found to reduce cholesterol levels in many people. Since high cholesterol is a risk factor for heart disease and stroke, statins save lives. They reduce the amount of cholesterol made by the liver and help the liver remove cholesterol that is already in the blood. Statins also reduce inflammation in the arterial walls that can lead to blockages that damage the heart and brain.

Like other prescription drugs, the safety and efficacy of statins were tested in accordance with FDA regulations in clinical trials. After a prescription drug is approved, government regulations and common sense require doctors to monitor the health and blood chemistry of their patients. This provides data on the types of adverse side effects and how often they occur. The data can also show that the drug has additional, unexpected benefits.

In the case of statins, they also lower triglycerides and inhibit the formation of new blood vessels (angiogenesis) that cancer cells need if they are to migrate (metastasize) to other parts of the body and become deadly. So, statins save lives by helping to prevent heart disease, stroke, and cancer. However, statins can cause severe muscle pain in some people. They often cause a key biochemical called coenzyme Q10 (CoQ10) to become depleted in muscle cells. It is a cofactor in the electron-transport chain, which is series of oxidation and reduction (redox) reactions that produce energy in the form of adenosine triphosphate (ATP).

Most cellular functions depend on an adequate supply of ATP. So, CoQ10 is essential for the health of virtually all human tissues and organs. CoQ10 is also one an important lipid antioxidant. As such, it prevents the production of free radicals that damage proteins, lipids, and DNA. In many disease conditions connected with increased production of free radicals and reactive oxygen species, the concentration of CoQ10 in the human body decreases. A deficiency of CoQ10 leads to a dysfunctional respiratory chain, which decreases the efficiency of cells. So, many people who take statins take one form or another of CoQ10 (such as Qunol) to prevent muscle pain. However, clinical trials have produced mixed results1-2.

Metformin (Glucophage®) is another example of a drug with beneficial side effects3-4. It was originally approved to help pre-diabetics and people with type-2 diabetes (T2D) control their glucose levels. It is the first line treatment for T2D. Metformin may also be useful in treating other diseases and possibly even slowing down aging. It reduces the incidence of cancer and mortality while helping people retain proper cognitive function. So, metformin favorably influences metabolic and cellular processes that are closely linked to the development of age-related problems, such as inflammation and cellular senescence. However, it does cause stomach discomfort, diarrhea, dizziness, and muscle pain in some people.

It may also affect aging by activating an enzyme called AMP-activated protein kinase (AMPK) and by reducing DNA damage. Increasing the activity of AMPK can prevent and possibly reverse the life-shortening effects of aging. Some scientists are beginning to refer to AMPK as a suppressor of aging itself. As AMPK decreases as we age, we become less energetic and more obese, while becoming increasingly vulnerable to cancer and diseases associated with impaired DNA and protein function. As a person accumulates abdominal fat, this leads to reduced insulin sensitivity, system-wide smoldering inflammation, and metabolic syndrome. This, in turn, can lead to many forms of cancer, as well as cardiovascular, neurodegenerative, and autoimmune diseases (including T2D).

The modern Western lifestyle, with its overabundance of nutrients and low level of physical activity, exacerbates this. When a person’s caloric intake is too high and/or physical activity is too low, AMPK activation decreases. As a result, cells decrease their energy-releasing ATP-generating activities and shift to energy-storing processes that generate new fat deposits and make excess new glucose. Moreover, energy inefficiency eventually leads to the dysfunctions that are often described as inevitable diseases (or symptoms) of aging. So, restoring the activity of AMPK in the elderly may not only increase longevity but also help to fight the symptoms of aging. This hypothesis was supported by a clinical study in which subjects with T2D either received metformin (which activates AMPK) or placebo. They were compared to subjects who did not have T2D. It was found that the subjects who were diabetic and received metformin lived a median of 15% longer than did matched controls without diabetes.

So, metformin favorably influences metabolic and cellular processes that are closely linked to the development of age-related problems, such as inflammation and cellular senescence. Since it is so inexpensive and easy to obtain, metformin could be especially useful in countries where many people don’t have much money.

However, metformin is not sufficiently effective for everyone. For such people, Ozempic®, Wegovy® or Rybelsius® can be prescribed5-6. All three drugs contain the same active ingredient, semaglutide. When combined with proper diet and exercise, they can lower blood glucose and reduce the risk of major cardiovascular events such as heart attack, stroke, or death in adults with type 2 diabetes with known heart disease7-8. Ozempic® is injected once weekly at a dose of 0.5, 1.0, or 2.0 mg once weekly, depending on the needs of the patient. Wegovy® is injected at a dose of 2.4 mg when used for weight loss. Rybelsius® tablets containing 7 or 14 mg of semaglutide are also available. Their most common side effects of semaglutide are nausea, vomiting, diarrhea, stomach (abdominal) pain, and constipation. Less common, but sometimes severe side effects include thyroid tumors, pancreatitis (inflamed pancreas), changes in vision, hypoglycemia (low blood sugar), kidney failure, allergic reactions, and gallbladder problems.

Semaglutide influences blood glucose levels by binding to a specific receptor on cells in the lining of the small intestines (L-cells), as well as subcutaneous fat, neutrophils, the liver, pancreas, central nervous system, and kidneys. This receptor binds the hormone called glucagon-like peptide-1 (GLP-1). GLP-1 is produced in the gut and is released into the bloodstream in response to food consumption. It reduces appetite and increases the secretion of insulin when it binds to its receptor. So, the stomach is an endocrine organ as well as an organ in the digestive system. When the body does not produce sufficient GLP-1, agonists such as semaglutide can bind to the receptor and have the same effect. This is different than the way that metformin acts. So, Ozempic® Wegovy® or Rybelsius® can be given as a monotherapy or in combination with metformin or insulin. It is highly advisable in people who have a cardiovascular disease, especially atherosclerosis. Semaglutide increases the endocrine activity of epicardial fat, and it has antithrombotic properties. Moreover, it decreases inflammation and atherogenesis.

Obesity, inflammatory and metabolic disorder can lead to dysfunctional adipose tissue, insulin resistance and cardiovascular disease6. Neutrophils from the immune system communicate with adipose cells and infiltrate them. Chronic inflammation due to obesity leads to higher infiltration of neutrophils, atherosclerosis and heart disease. Metabolic syndrome (a high body mass index) was estimated to cause 4 million deaths in 20159. More than two-thirds were caused by cardiovascular disease.

However, there is currently a shortage of the semaglutide that is needed to make Ozempic®, Wegovy® and Rybelsius®. This has caused complaints and controversy. Many people think that T2D is a much bigger and more imminent threat to patients’ lives than obesity and should be given priority. In the meantime, the producer of these drugs, Novo Nordisk is working three shifts, 24 hours per day, seven days per week to make as much semaglutide as possible.

Notes

1 Taylor, B. A., Lorson, L., White, C. M., & Thompson, P. D. (2015). A randomized trial of coenzyme Q10 in patients with confirmed Statin Myopathy. Atherosclerosis, 238(2), 329-335.
2 Caso, G., Kelly, P., McNurlan, M. A., & Lawson, W. E. (2007). Effect of Coenzyme Q10 on Myopathic Symptoms in Patients Treated With Statins. The American Journal of Cardiology, 99(10), 1409-1412.
3 Metformin (Glucophage) May Extend Lifespan.
4 Metformin and aging.
5 Cigrovski Berkovic, M., & Strollo, F. (2023). Semaglutide-eye-catching results. World Journal of Diabetes, 14(4), 424–434. doi:10.4239/wjd.v14.i4.424.
6 García-Vega, D., et al. (2024). Semaglutide modulates prothrombotic and atherosclerotic mechanisms, associated with epicardial fat, neutrophils and endothelial cells network. Cardiovascular Diabetology, 23(1).
7 Lincoff, A.M. et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. [New England Journal of Medicine] Vol. 389.24, p. 2221-2232, 2023.
8 Novomedlink, 2024.
9 The GBD 2015 Obesity Collaborators. (2017, July 6). Health Effects of Overweight and Obesity in 195 Countries over 25 Years. New England Journal of Medicine, 377(13), 13-27. doi:10.1056/NEJMoa1614362