Hello Alpha Reddit AMA on Weight Loss Medication

We Invited Reddit to an Ask Me Anything About Weight Loss Medication — Here’s What Happened

With medications like Ozempic and Wegovy making headlines from the Oscars to viral TikToks, we at Hello Alpha wanted to clear up the myths and misconceptions around the new generation of prescription medications. Our Chief Medical Officer, Dr. Mary Jacobson (affectionately known as Dr. J), recently hosted an “Ask Me Anything” (AMA) thread on Reddit to give meaningful explanations about how these medications work and how they can impact women’s health. As a trained OB/GYN, Dr. J answered questions about how these medications can affect fertility, menstrual symptoms, and more.

If you missed the live AMA, don’t worry — we’ve summarized the highlights below.

Q: I’ve heard a lot about the stomach side effects of Ozempic, like diarrhea and nausea. Are those potentially dangerous or just annoying?

A: Nausea, vomiting, diarrhea, constipation and belching/bloating are the most reported side effects of Ozempic. These side effects can definitely be annoying and uncomfortable, but not necessarily serious.

Nausea is the most common side effect when first starting an injectable medication for weight loss. Nausea decreases over time for most people, as your body gets used to the medicine. Here are a few tips:

• Eat bland, low-fat foods, like crackers, toast, and rice
• Eat foods that contain water, like soups and gelatin
• Don’t lie down after you eat (This can induce reflux symptoms.)
• Go outside to get some fresh air

If the above strategies do not help, you can step down on the dosage which you were able to tolerate.

More serious but rare side effects include gallbladder problems and pancreatitis (inflammation of the pancreas). Symptoms of pancreatitis include:

• Severe belly pain that may spread to your back or chest (it may feel worse after you eat)
• Nausea
• Vomiting
• Rapid heart rate
• Fever

Please contact your healthcare provider immediately if you experience these side effects. Every body is different, and any usual side effects or symptoms you notice deserve care from your provider. If you’re experiencing severe side effects, seek immediate care and call 911 (if you’re in the US) or any emergency services in your area.

Q: Have there been any studies on the link between the use of semaglutides and fertility? Any concerns you see for use ahead of trying to conceive?

A: Fertility is complex, with many different factors that impact it. Being severely overweight or underweight can impact fertility, as well as hormones and other aspects of a person’s health. To my knowledge, there aren’t any studies looking at the relationship between fertility and using semaglutides. For anyone looking to become pregnant who is using semaglutides, I recommend that they speak with their healthcare provider before conceiving.

Data from clinical trials with semaglutide use in pregnant patients are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

Novo Nordisk created a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to semaglutide during pregnancy. Pregnant women exposed to Wegovy and healthcare providers are encouraged to contact Novo Nordisk at 1–800–727–6500.

When a pregnancy is recognized, providers should advise the pregnant patient of the risk to a fetus, and discontinue the semaglutide.

Excess weight during pregnancy is associated with several pregnancy and childbirth complications and the best way to lose weight pre-pregnancy is by making changes in your diet and being more physically active.

Q: I get really bad reflux with semaglutide. What’s the latest you recommend I eat before going to bed at night? I find acid tends to rise at night even with raising my bed.

A: Excess body weight or excess adiposity is an important risk factor for the development or worsening of reflux. Weight loss is an effective lifestyle modification in improving reflux. Lifestyle modifications to help improve reflux related symptoms include elevating the head of the bed which you are already doing and:

• Avoid eating at least 3 hours prior to sleep time
• Avoid sleeping on your right side
• Turn off lights when enter bed and minimize disturbances to a normal sleep
• Improve sleep hygiene, in general, because sleep reduces reflux symptoms by suppressing relaxation of the lower part of your esophagus

Work with your health care provider to add or modify medication to treat reflux symptoms, as needed. They may recommend a procedure called an upper endoscopy depending upon the severity of your symptoms and whether or not your symptoms respond to medication.

Q: Have you heard a lot of patients reporting an increase or new onset of anxiety starting Ozempic? I’ve read the package insert top to bottom (I’m a nerd lol) and there’s no mention of anxiety other than symptoms intertwined with hypoglycemia, which I’ve ruled out. I’ve searched for aftermarket reports and studies but I’m not finding anything substantial. Side note…as an ER nurse I tip my hat to you. The speciality of OB/GYN is not for the faint of heart. I applaud your career and training.

A: Thank you for your kind words, and for what you do for your patients! I’m wishing you all the best, and that you find time to take care of yourself, too. A high-stress environment can have a large impact on mental health. I understand your question is about anxiety specifically, but I wanted to share the broader research that’s been done so far.

Molecular studies on the mechanisms of action of antipsychotics and antidepressants, and of hypoglycemic drugs used for metabolic disorders, are beginning to show that some key enzymes can regulate aspects of both energy management and psychopathology.

The STEP clinical trials on semaglutides Ozempic and Wegovy, which has the most robust and longest term data to date, excluded people with the following mental health issues:

• History of major depressive disorder within 2 years before screening
• History of major depressive disorder within 2 years before screening
• Diagnosis of other severe psychiatric disorder (for example, schizophrenia, bipolar disorder)
• A Patient Health Questionnaire-9 score of ≥15 at screening
• A lifetime history of a suicidal attempt
• Suicidal behavior within 30 days before screening
• Suicidal ideation corresponding to type 4 or 5 on the Columbia-Suicide Severity Rating Scale within the past 30 days before screening

Early studies show possible antidepressant and anti-anxiety effects of GLP1s like Ozempic. A Regulatory Post Marketing Surveillance (rPMS) Study of Ozempic (semaglutide) is ongoing. Nonetheless, we recognize individual responses to medication varies.

Q: Are there any good methods to overcome stalls? I lost 40 over about 16 months, however, I would like to lose another 25 and have been essentially stagnant since last fall.

A: Congratulations on your progress so far! Losing weight and maintaining that loss are great accomplishments. A concept called set point theory involves our brains telling us how much fat to store. We can modify our individual set points with lifestyle interventions like dietary changes and adding exercise. As your body adjusts to a different set point, you may experience a stall or plateau. Physiologically, what is happening is that your resting metabolic rate drops dramatically and your body is resisting any further drop in weight.

In this case, focusing on habits can help. Studies show that people can lose, on average, 4–7% of their body weight with lifestyle changes. Lifestyle changes which are effective in losing and maintaining weight include:

• Eat a diet with a focus on of whole and plant-based foods
• Increase in physical activity
• Develop strategies to manage stress
• Form and maintain relationships
• Improve your sleep
• Avoid risky substances, e.g., excess alcohol, prescription medications which can cause weight gain

Q: Can you explain compounded semaglutide? There is so much confusion over the source of compounded semaglutide and how compounding pharmacies work.

A: Semaglutide is a drug class which includes the brands Ozempic and Wegovy. Novo Nordisk owns multiple patents protecting its medications that use semaglutide, including the drugs Ozempic and Wegovy.

Supply and cost constraints have led some companies to formulate compounded semaglutides. Compounded medications are not FDA-approved. The FDA does not verify their safety, effectiveness, or quality of compounded drugs before they are marketed. In addition, according to the FDA, poor compounding practices can result in serious drug quality problems, such as contamination or a drug that contains too much active ingredient.

My team of providers and I echo the sentiment of many health care providers and do not prescribe compounded semaglutide for patients, since we cannot be sure what ingredients are in compounded semaglutides or how the agents work compared to the original drugs.

Q: What do you recommend for women who want to lose weight and are currently perimenopausal heading into menopause? Not a great time to try and lose weight but the weight keeps creeping up.

A: Weight gain is a symptom of menopause experienced by 60%–70% of midlife women and people assigned female at birth. On average, women gain about 1.5 pounds per year during the midlife period (age 50–60 years), independent of their initial body size or race/ethnicity.

Acceleration of fat mass increase and lean mass decline occurs during the menopausal transition, and a stabilization of body composition postmenopause. This is important because shifts in fat distribution and in body composition that occur during the menopausal transition are associated with increased cardiometabolic risk factors, including elevated blood pressure, elevated low-density lipoprotein, and obesity.

Reasons for weight gain in the menopause transition is that physiological factors, including decreased estrogen concentration and changes in body fat distribution associated with the menopausal transition, as well as chronological aging, may make midlife women more prone to weight gain and subsequent obesity.

The first steps recommended for women experiencing weight gain with menopause are lifestyle changes such as:

• Eat a diet with a focus on of whole and plant-based foods
• Increase in physical activity
  - Weight training to strengthen your muscles, burn calories, and fight osteoporosis
  - Brisk walking
  - Jogging
  - Biking or spinning
  - Aerobics
  - Dancing
  - Tennis
  - Weight training
  - Interval training
• Develop strategies to manage stress
• Form and maintain relationships
• Improve your sleep
• Avoid risky substances, e.g., excess alcohol, prescription medications which can cause weight gain

Q: How can I convince my insurance company to cover some of these drugs? I’m fat, I’ve been fat, I’ve failed at a hospital sponsored bariatric weight loss program (nonsurgical). My numbers (a1c, cholesterol, thyroid, etc) all come back in normal ranges but no weight loss. My joints are starting to be affected, though, so I’d like to work on weight loss, but it feels impossible without my insurance covering something like this.

A: I empathize and agree with your point. Obesity or excess weight is not a lifestyle choice or a lack of willpower. The Obesity Medicine Association defines obesity as “a chronic, relapsing, multifactorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”

Unfortunately, according to a U.S. Government Accountability Office report, coverage of weight loss drugs varied across different types of health insurance, including Medicare and Medicaid. Plans cited factors such as low consumer demand and strong evidence supporting other treatments in their coverage decisions.

I recommend that you use resources from trusted organizations like the Obesity Action Coalition (OAC) to:

• Know your insurance benefits for weight loss medications
• Understand the prior authorization (PA) process
• Denial of an initial PA is very common. Read the details of why your PA was denied and consider working with your clinician to submit an appeal
• Get involved with advocacy organizations like the OAC

Q: I’ve been taking Wegovy for 19 weeks and only lost 11–12 lbs. I just took my third 2.4mg dose last night. I have approximately 80 lbs to lose, do you think switching to Mounjaro would give greater results?

A: From what you describe, this sounds like a titration (changing medication dose) issue. Wegovy comes in 5 different dose strengths. Most people will start Wegovy at a dose of 0.25 mg once a week and increase the dose every 4 weeks until they reach the full dose of 2.4 mg. Clinical guidelines recommend an adjustment to weight loss medication if someone has lost less than 5% of their body weight on the maintenance dose after 90 days. In other words, I recommend that you discuss an adjustment to weight loss medication with your healthcare provider, i.e., in your case, if you have lost less than 5% of your body weight on the maintenance dose of Wegovy 2.4 mg after 90 days.

Q: I’ve heard that there are other drugs in the same class as semaglutide and tirzepatide in the pipeline that may be even better. Any truth to that?

A: Prior to the advent of Glucagon-like peptide 1 (GLP-1) such as liraglutides and semaglutides and the GLP-1/gastric inhibitory polypeptide (GIP) tirzepatide, long-term pharmacotherapy to achieve body weight normalization along with suitable tolerability and safety remained an insurmountable challenge.

Medications in clinical trials which are under investigation for treating type 2 diabetes mellitus and/or obesity commonly target two-three receptors. We are living in an exciting time of targeted drug therapy to address excess weight as researchers close the achievable weight loss gap between medications and weight loss surgery.

Q: What is the safest way to combat extreme fatigue on this medication? I’ve been sleeping an easy 10–12 hours a night since starting.

A: I am unsure what medication you are taking for weight loss. However, semaglutides like Ozempic and Wegovy as well as tizepatide (Mounjaro) can cause fatigue and somnolence (drowsiness). However, I recommend that you identify all sources of fatigue.

Bear in mind that patients with excess weight have higher rates of obstructive sleep apnea. In people with obesity, fat deposits in the upper respiratory tract narrow the airway; there is a decrease in muscle activity in this region, leading to hypoxic and apneic episodes, ultimately resulting in sleep apnea which causes fatigue and somnolence.

Q: My girlfriend is 33, has endometriosis, and has been on Ozempic for 4 months now. So far, as she is losing weight her periods are getting worse. When she was a teen/young adult she would constantly vomit, have terrible cramps, and be physically exhausted on her periods. She used to take birth control to prevent them but she went off around age 25 and her symptoms decreased so she didn’t go back on it. Her doctor says there shouldn’t be any correlation between her period symptoms and taking Ozempic. What do you think is happening? She is afraid to titrate up.

A: The specific impact of semaglutides on the menstrual cycle is not yet well understood. The relationship between semaglutides, weight loss, and the menstrual cycle is complex.

Women and people who are assigned female at birth who have excess weight have a higher incidence of menstrual dysfunction and anovulation. As people lose weight, they may begin to ovulate and regularly menstruate. Initially, people who are not ovulating regularly and are taking semaglutides for weight loss may experience heavy menstrual bleeding due to the build-up of the endometrial lining (the innermost layer of the uterus). Eighty-five percent of people with polycystic ovarian syndrome have excess weight and the majority of these people do not regularly ovulate.

Your girlfriend’s recurrence of symptoms around her menstrual period may be recurring due to resumption of menses. If your girlfriend isn’t already doing so, I would recommend that she keep a detailed journal of her symptoms and when they occur may help her and her healthcare provider understand what’s happening. Menstrual issues deserve care and medical attention, especially when they interfere with daily life.

Q: What is a healthy amount of monthly weight loss with prescription medication? I’m on Wegovy, and seeing results monthly. However, given some of my dysmorphia and general anxiety surrounding weight/weight loss/eating, I yo-yo between happy with my weight loss and super sad. I’d love to have a legitimate number to refer to.

A: A healthy amount of monthly weight loss with prescription medication for people with excess weight is less than 10% of your body weight. More than that is concerning because of the potential for breakdown of muscle mass which can cause kidney damage. Remember that weight loss is a lifelong journey and not a sprint. As a rule of thumb, 1–2 pounds of weight loss per week is a good target.

A concept called set point theory involves our brains telling us how much fat to store. We can modify our individual set points with lifestyle interventions like dietary changes and adding exercise. As your body adjusts to a different set point, you may experience a stall or plateau. Physiologically, what is happening is that your resting metabolic rate drops dramatically and your body is resisting any further drop in weight. Once you stop an intervention, your body will return to its prior body fat mass set point and you’ll gain weight. The scientific term for this physiologic process or “yo-yoing” is called weight cycling.

Q: I recently started Ozempic but I am thinking of quitting. I’m sick three out of four days. I took my fourth shot today and so far I haven’t lost one pound. Is that normal?

A: Weight loss is a lifelong journey and not a sprint. Immediate weight loss is uncommon. Working with your provider to step down on the dosage which you were able to tolerate or switching medications, as needed, would be my recommendation. Every body is different, and side effects and symptoms deserve care from your provider. These medications can cause serious but rare side effects including gallbladder problems and pancreatitis which require immediate attention.

Q: If you do not have any side effects and have been on semaglutide for two weeks at the 1.0 ml level, can you up it to 2.0 ml at week 3? My doctor told me at 2.0 is when you lose weight. I am ready to lose more weight.

A: It’s great that you’re not experiencing side effects. Clinical guidelines recommend a dose escalation of a minimum every 4 weeks to minimize gastrointestinal adverse reactions. Weight loss is a lifelong journey, not a sprint. These guidelines are meant to keep your whole health in mind while you take this medication. I encourage you to keep sharing progress with your doctor.

Q: If a patient is losing weight steadily on a lower dose of semaglutide, should they increase per the recommended titration schedule or should they remain at the lower dose until it no longer becomes effective?

A: Patients who achieve adequate results at a lower dose of a semaglutide can certainly remain at the lower dose. Patients should work with their healthcare provider to make a shared treatment plan.

Q: I am insulin resistant and hesitant to try semaglutide because the Ozempic/Wegovy website says that it works by triggering insulin to reduce blood sugar, which is the last thing I need. Yet it’s prescribed for people with insulin resistant PCOS. Can you explain its mechanism for people with insulin resistance or should we avoid it? My doctor says to ignore the website and that that’s not how it actually works unless you’re diabetic.

A: Semaglutide works by mimicking the action of GLP-1, a naturally occurring hormone that helps to regulate blood glucose levels. Semaglutides reduce insulin resistance by binding to and activating the GLP-1 receptor, which stimulates insulin secretion and lowers glucagon secretion when blood glucose levels are high.

Semaglutides reduce body weight through distributed activation throughout the brain. Specifically, semaglutides directly activate GLP-1 receptors in neurons involved in appetite in the hypothalamus and the hindbrain. Secondarily, semaglutides activate neurons in key appetite-modulating relay stations (e.g. parabrachial nucleus) via several independent brain nuclei. In other words, semaglutides affect the brain’s appetite centers to reduce the feeling of hunger. It treats and does not worsen insulin resistance, just like semaglutides treat diabetes.

Q: Is Ozempic needed for life, meaning weight will go back up if the medication is stopped? What are the long term risks of using Ozempic?

A: A concept called set point theory involves our brains telling us how much fat to store. We can modify our individual set points with lifestyle interventions like dietary changes and adding exercise. As your body adjusts to a different set point, you may experience a stall or plateau. Physiologically, what is happening is that your resting metabolic rate drops dramatically and your body is resisting any further drop in weight. Once you stop an intervention, your body will return to its prior body fat mass set point and you’ll gain weight. The scientific term for this physiologic process or “yo-yoing” is called weight cycling.

According to the Obesity Medicine Association:

1. The current standard of care with respect to obesity pharmacotherapy is that medications should be prescribed long-term.
2. Short-term use of obesity pharmacotherapy is not recommended as it has not been proven to provide a benefit.

Since semaglutides are relatively new medications, long-term risks of semaglutides are not known. Regulatory Post Marketing Surveillance trials are underway.

Clinical studies have proven that carrying extra fat leads to serious health consequences such as cardiovascular disease (mainly heart disease and stroke), type 2 diabetes, musculoskeletal disorders like osteoarthritis, and some cancers (endometrial, breast and colon). These conditions can cause premature death and substantial disability. Many doctors believe that the as yet unknown risks of taking semaglutides long term are outweighed by the health consequences of carrying excess weight.

Q: I have suffered from diarrhea since starting semaglutide 2.5 months back. My prescriber suggested injecting in my upper thigh vs. stomach. Also, splitting to 0.35 twice a week. Is that as effective?

A: I am sorry that you are having side effects from the semaglutide. Gastrointestinal side effects from semaglutides are common. I recommend that you continue to work with your provider to explore other reasons for diarrhea, review your dietary history, and step down on the dosage which you were able to tolerate or switch medications, as needed. Injection sites which the manufacturer recommends under the skin are in the upper arms, stomach (keep 2 inches away from belly button), or upper legs (front of thighs). The manufacturer specifically recommends against counting pen clicks to estimate the amount of drug to dispense because this method is inaccurate. Only use the dose counter and dose pointer which shows how many mg you select per dose.

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