Weight Loss Treatment Side Effects and Common Complaints: Separating Fact from Fiction

In this blog, I will address the reported side effects and complications associated with treatment using the Glucagon-Like Peptide-1 Receptors (GLP-1R) agonists including Semaglutide, Wegovy, Ozempic, and Mounjauro. These medications have been used in diabetics for 10 years and there are a significant number of high-quality research studies and reviews that we’ve relied on in providing this review with recommendations.

Side Effects Associated with the Medication

Nausea and Vomiting: Nausea is the most common side effect and approximately 50% of patients have at least one episode of nausea while on therapy. Many patients discontinue the medication because of significant nausea or vomiting. In our experience, the most common reasons patients end up in the ER are:

• They are started on the diabetic dose (0.625mg/week) rather than the non-diabetic dose (0.25mg/week);
• They are sensitive to the medication but the provider does not adjust the dose to be more conservative;
• The medication is increased more often than every 4 weeks – it takes 4 weeks for the medication to reach steady-state so your dose should never increase more often than every 4 weeks except for rare circumstances (patients who are less sensitive to the medication).

Most providers will provide an anti-emetic like Zofran to help with nausea, but this is not the most effective way to manage patients who are sensitive. In these cases, we reduce the dose and create a slower dose escalation than the FDA-recommended dosing for non-diabetics. The benefits of this approach are that the lower dose reduces nausea and vomiting, and treatment is less costly because patients are using less medication. We have a significant number of patients who should be at the maximum dose of 2.5mg per week but stay at a lower dose (40-60% of the maximum dose) for months because the medication is working well, and they don’t need to increase the dose. We also believe that regular exercise increases the effectiveness of the medication.

Constipation and diarrhea: These are relatively common side effects but improve with time on the medication. In general, constipation is usually only reported by patients who have had problems with constipation in the past. We recommend using an over-the-counter supplement that has worked for them in the past. You can consider using Mag07, a magnesium-based motility agent (available on Amazon by clicking here).

Elevated Heart Rate: Some patients may see their resting heart rate increase 10-20 beats per minute, but this is not associated with any heart dysfunction or arrythmias. In fact, a recent clinical trial showed that Wegovy (trade name for semaglutide) reduced heart attack risk by 20%, illustrating the benefits of decreasing caloric intake and losing weight.

Acid Reflux: There are two ways that the stomach produces acid – resting acid secretion and food-stimulated acid secretion. Since the medication can slow stomach motility, it can result in food remaining in your stomach when you go to bed. If that happens, the food can stimulate acid secretion and give you acid reflux. We recommend not eating within 3 hours of bedtime and starting an H2 blocker like Zantac 350 because the H2 blockers inhibit food-stimulated acid secretion. Proton pump inhibitors like Omeprazole/Prilosec are less effective than the H2 blockers because they inhibit resting acid secretion, not food-stimulated acid secretion.

Acute Pancreatitis: Early small studies reported an increased risk of acute pancreatitis. There are now meta-analysis showing that there is no increased risk of acute pancreatitis or pancreatic cancer. We have treated over 400 patients and have not seen a case of acute pancreatitis.

Medullary Thyroid Cancer: High doses of the medication given to rats and mice have been shown to stimulate this tumor, which is normally extremely rare in humans (most common are papillary and follicular subtypes). Since these early studies, researchers have learned that rats and mice have numerous GLP-1 receptors in the medullary cells of the thyroid gland, whereas humans have very few. It is a theoretical risk but considered highly unlikely and there are no reported cases of medullary thyroid cancer in human patients taking these medications.

Gastroparesis and bowel obstruction: this is a functional disorder of the stomach in which it is paralyzed and no longer grinds up food or propels it into the small bowel using peristalsis. We do not believe that the weight loss medications cause gastroparesis. The number one cause of gastroparesis is diabetes and the case reports (only 17 case reports as of the publication of the blog) of the medication causing gastroparesis are in diabetic patients who are taking the medication. We believe that these patients have underlying gastroparesis and slow bowel motility, and the medication makes it worse because it further slows stomach and small bowel peristalsis. We also believe that the few cases of bowel obstruction with the medication occurred because of underlying poor motility related to diabetes that is made worse by the medication.

Ileus: this is a temporary paralysis of the stomach muscles where patients have the same symptoms as gastroparesis, but the stomach recovers over a short time period. Ileus often occurs after surgery, both the anesthetics and pain medications can cause ileus of the stomach. Ileus can also occur after an infection of the stomach or with food poisoning. We see this in less than 1% of patients taking the medication and all of the cases have resolved within 24 hours. Symptoms include feeling full several hours after eating, abdominal bloating, nausea, acid reflux, and foul-smelling burps. Our recommendation is to not eat any food and only take small sips of water or coffee until the symptoms resolve. We can also prescribe a prokinetic medication to speed up recovery.

Side Effects Associated Weight Loss (not the Medication)

Hair Loss: This is a known consequence of rapid weight loss and not directly caused by the medication. There are many studies that link hair loss to rapid weight loss, calorie restriction, nutrient deficiencies, and psychological stress. Calorie restriction with gradual weight loss is associated with improved hair regrowth and retention. We recommend limiting weight loss to 1 pound per week on average, taking supplements that include a multivitamin, moderate exercise (extreme exercise is also associated with hair loss), a balanced diet that includes protein and carbohydrates like the Mediterranean diet (low calorie diets such as Atkin’s and Keto are associated with hair loss), and minimizing stress. There are also several effective treatments, including supplements and growth injections.

Read more about hair loss and treatment with supplements and growth factor injections by clicking here.

Supplements we recommend:

• Vitamin C
• Methyl B Complex
• Vitamin D3
• Melatonin Puritan’s Pride Super Strength
• Resveratrol
• Quercetin
• PreserVision AREDS 2 Eye Vitamin & Mineral Supplement
• DIM

Changes in Menstrual Cycle: This is also a known consequence of weight loss, as a woman’s estrogen level can change based on the amount of body fat. Estradiol levels decrease in proportion to the reduction in body weight. Significant (more than 20%) or rapid weight loss can cause irregular periods or amenorrhea, which is not having a period. Another cause is menopause, in which the ovaries produce significantly less estrogen than a woman in her 30’s. We recommend hormone replacement with bio-identical hormones for women who are postmenopausal because of the numerous health benefits, noting that the health benefits are greatest when hormone replacement is initiated within 10 years of menopause.

Read more about hormone replacement for women by clicking here.

Gallbladder disease: It is unclear if the increased reports of gallbladder disease including gallstones, acute cholecystitis, and rates of cholecystectomy in patients on these weight loss treatments is related to the medication or weight loss. There are several clinical studies that suggest these entities are unrelated to the medication and a consequence of weight loss, similar to the conditions above.

Common Complaints You Will See Online

“I took the medication and lost weight, but when I stopped I put the weight back on”: This might be the most concerning complaint from patients who have tried the medication. Based on our experience, we believe there are three main contributors to putting weight back on after stopping treatment.

• First is that patients go on a starvation or crash diet and lose more than 2 pounds per week. At that rate, 50% of the weight loss is fat but the other 50% is muscle. This contributes to weight gain because muscle affects your metabolic rate, which is how many calories you burn in a day. Muscle burns calories when you work out and when you are asleep. If you lose 30 pounds and 15 pounds is muscle, then you will burn fewer calories and be more likely to put the weight back on.
• Second is that the provider did not talk to the patient about their goals during treatment, acting as if the medication was the solution. We use the medication as a tool that you can use to assist with weight loss, but to keep the weight off, you must work every day to develop the behaviors and habits that will allow you to keep the weight off when you stop taking the medication. This includes a healthy diet, regular exercise (both aerobic and anaerobic), adequate sleep (at least 7 hours a day), hormone replacement if you are deficient in testosterone (both men and women), and reducing stress.
• Third is that patients stop the medication when they achieve their goal weight without tapering off or going on a maintenance dose. A taper is when you change injections to be every month instead of every week, and slowly decrease the dose over time. A maintenance dose is when change injections to be every month instead of every week, using the same dose of your last weekly injection. We recommend going on maintenance for 6-12 months after achieving your goal weight because your body has more time to adjust to the new weight.

“I feel fatigued, anxious, and/or panicky on the medication”: This typically indicates the patient is losing too much weight too quickly, i.e. a starvation or crash diet. Most patients who are in a mild calorie deficit (300-500 calories a day) experience increased energy because of the cells in the body becoming more efficient at housekeeping activities such as mitochondrial homeostasis (repairing damaged mitochondria, creating new mitochondria, and eliminating dysfunctional mitochondria – the power plant of the cell). It can be difficult to associate these symptoms with low calories because the medication suppresses the hunger signal. People who do weight-bearing exercises, particularly men who are regularly doing heavier exercises like bench press, squats and deadlifts, may notice the weights they use go down over time – a sign that you are losing muscle mass in addition to fat. We recommend adding 200-300 calories to your daily diet.

CONCLUSION

There has never been a more effective weight loss treatment than the GLP-1R agonists, including semaglutide. The only known intervention that’s more effective is bariatric surgery, which can result in a decrease in 25% of a patient’s body mass index (BMI). The GLP-1R agonists can result in a 15% decrease in BMI without any of the complications associated with bariatric surgery, including death. More importantly, because these medications reduce calorie excess and promote healthier food choices, when coupled with exercise, they can also reduce the rates of most of the most common causes of death in this country including cardiovascular disease like heart attack and stroke, metabolic disorders like diabetes and fatty liver, Alzheimer’s disease, cancer, renal disease and liver disease. We predict that more patients will be taking this medication in the next 5-10 years for the health benefits, not just weight loss.

REFERENCE

Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1

Read about how I lost 17 pounds in 10 weeks semaglutide by clicking here 

Read about how I maintained the weight loss using maintenance dosing by clicking here

Read a success story from one of our female patients by clicking here 

Read a success story from one of our male patients by clicking here