Feature Article: May 2023 – Contraindications and Side Effects of the New Effective Weight Loss Drugs

Contraindications and Side Effects of the New Effective Weight Loss Drugs

Jeff Morris

Semaglutide — better known by the brand names Ozempic, Wegovy, and Rybelsus — was originally intended for people with Type 2 diabetes. But the medications are frequently prescribed for weight loss, as well, as is tirzepatide, sold under the brand name Mounjaro. Multiple side effects have been identified, with new possible unwanted consequences continuing to be noted. How effective is this treatment for weight loss, how serious are the side effects, and can these side effects be lessened?

You may know semaglutide as Ozempic, an injectable medication used in people with Type 2 diabetes. Ozempic can help manage blood sugar, and it can also lower the risk of heart attack and stroke in those who also have heart disease. It is also available as an oral pill, called Rybelsus. Wegovy, a higher-strength version, is approved to help people lose weight.

Semaglutide works by mimicking a gut hormone that causes the pancreas to release insulin, blocks the liver from releasing sugar, and slows down the speed at which food leaves the stomach. While these actions can be beneficial for Type 2 diabetes and weight loss, they can also cause some side effects.

Some semaglutide side effects can be bothersome and make the medication difficult to tolerate, but they usually subside over time. Although rare, there are also some serious side effects. According to the Mayo Clinic, some of the less common side effects patients should report to their doctor immediately include belching; a bloated, full feeling; excess air or gas in the stomach or intestines; gaseous stomach pain; heartburn; passing gas; recurrent fever; stomach discomfort, fullness, or pain; and yellow eyes or skin. 

There are some side effects that may occur but usually do not need medical attention; they may go away during treatment as the body adjusts, but they should be reported if they continue or are bothersome. The most common is diarrhea. Less common are constipation and hair loss. Rare side effects include change in, or loss of, taste; bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site.

Additional rare side effects include a burning feeling in the chest or stomach; indigestion; stomach upset; and tenderness in the stomach area. 

There is yet another long list of other possible side effects, the incidence of which is not known. Alphabetically, these include anxiety; blurred vision; chest tightness; chills; cold sweats; confusion; cool, pale skin; cough; darkened urine; difficulty swallowing; discouragement; dizziness; fast heartbeat; feeling sad or empty; headache; hives, itching; increased heart rate; increased hunger; irritability; lack of appetite; large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs; loss of consciousness; loss of interest or pleasure; nausea; nightmares; pains in stomach, side, or abdomen, possibly radiating to the back; puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue; redness of the skin; seizures; shakiness; skin rash; slurred speech; tiredness; trouble breathing; trouble concentrating; trouble sleeping; unusual tiredness or weakness; and vomiting.

Besides all of these, the National Library of Medicine’s MedlinePlus has what it categorizes as an important warning: Semaglutide injection may increase the risk that you will develop tumors of the thyroid gland, including medullary thyroid carcinoma (MTC; a type of thyroid cancer). Laboratory animals who were given semaglutide developed tumors, but it is not known if this medication increases the risk of tumors in humans. Tell your doctor if you or anyone in your family has or has ever had MTC or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2; condition that causes tumors in more than one gland in the body). If so, your doctor will probably tell you not to use semaglutide injection. If you experience any of the following symptoms, call your doctor immediately: a lump or swelling in the neck; hoarseness; difficulty swallowing; or shortness of breath.

As was noted, hair loss is one of the less common side effects that is not considered to need medical attention, but it has received considerable attention in social media posts, and it is listed as a possible consequence by at least one of the manufacturers. 

An April 22 report by Kaitlin Sullivan of NBC News quoted Dr. Susan Massick, a dermatologist at Ohio State University, who has seen patients who have lost hair following weight loss surgery. “What is really striking for folks is that there are no scalp symptoms,” said Dr. Massick. “It doesn’t hurt, there’s no itching, but you can run your hands through your hair and you have a handful of hair. It can be really disconcerting to see that.”

She also quoted Dr. Vijaya Surampudi, assistant director of the UCLA weight management program in Los Angeles, who said although hair loss a shocking side effect, it’s relatively uncommon among people taking the medications. “Hair loss is unlikely related to the drugs,” said Dr. Surampudi, who has counseled patients who have experienced hair loss while on the medications, “but more likely related to weight loss that is a result of these drugs.”

Indeed, hair loss is common with major weight loss. Hair loss during a time of stress, whether it is pregnancy, divorce or dramatic weight loss, is extremely common, and even has its own name: telogen effluvium.

According to the NBC News report, hair loss is not listed as a side effect of Ozempic, but in clinical trials for Wegovy, 3% of people reported hair loss, compared to 1% of people who got a placebo. (While Ozempic and Wegovy are the same drug, Wegovy is given at a higher dose.) In a clinical trial for tirzepatide’s effects on weight loss, nearly 6% of people taking the highest dose reported alopecia, compared to 1% of those who got a placebo. Tirzepatide drugmaker Eli Lilly said in a statement that the hair loss seen in the clinical trial was generally short-lived. “Hair loss is a side effect that has been associated with significant weight loss in many previous clinical trials for obesity treatment,” the statement said.

A long time participant in Age Management Medicine conferences and member of the AMMG Advisory Board, Dr. Mickey Barber of Better Life Carolinas, told the E-Journal, “We are using semaglutide and tirezepatide in our practice, and have been for several months. In general we are very pleased with the results, which includes weight loss and better glucose control.”

Dr. Barber said the main issue she has seen with semaglutide is, “the long list of GI side effects and our inability to really predict who will get them and how debilitating they may be. Most commonly we have seen nausea, heartburn and constipation. Usually patients push through these and but we have had patients stop the medication due to nausea.” 

Despite these problems, Dr. Barber said that overall, “I really think that these medications could be a game changer for obesity and type 2 diabetes, with fewer side effects as new generations hit the market.”

Dr. William Clearfield, Medical Director, Clearfield Family Medicine in Reno, Nevada, Executive Director of the American Osteopathic Society of Rheumatic Diseases, and a leading figure in family and integrative medicine, gave an extensive presentation on The New Face of Weight Loss at the AMMG Conference in April. He called Semaglutide a game changer, pointing to a 14.9% average weight loss of 68 weeks, with 32% of patients losing 20% of initial body weight, and 70% of patients losing at least 10% of initial body weight.

Dr. Clearfield repeated the same warnings about side effects, referencing a Medscape listing:

  • Nausea (44%)
  • Diarrhea (30%) 
  • Vomiting (24%) 
  • Constipation (24%) 
  • Abdominal pain (20%) 
  • Headache (14%) 
  • Fatigue (11%) 

He noted semaglutide is contraindicated if there is a personal or family history of medullary thyroid cancer, but that routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with semaglutide. Other weight loss drug issues he noted are cholelithiasis; hypoglycemia; heart rate increased (mean 1-4 bpm) 10-19 bpm (41%) and 20 bpm (26%); and suicidal behavior and ideation.

But the biggest problem Dr. Clearfield noted with Semaglutide is the cost: it is $1500-$1700/month at retail, and with discount coupon, approximately $1350/month.

The biggest medical issue he found, similar to Dr. Barber, is nausea, with a 44% incidence of nausea severe enough to cause discontinuation of regimen. However, he said, “we can fix it!” and offered what he called his Weight Loss Game Changer that combines Semaglutide injections with Vitamin B6, which reduces nausea and vomiting up to 50% more than placebo.

Dr. Clearfield’s Improved Semaglutide Injection Plan comprises multiple elements, including his dosing and schedule for the Weight Loss Game Changer, combined with AMPK as a regulator of energy homeostasis and coordinator of metabolic pathways that balances nutrients with energy demands, along with different options for diet and exercise. 

“By making a few simple changes to a patient’s eating habits, we can attain short term benefits in the form of weight loss, and instill lifelong habits leading to physical, mental and spiritual well being,” he said.