Though I'm not obese, I'm planning on taking semaglutide for at least 3 months, pending any significant side effects. I'm 5'11'' and currently weigh around 200lbs. My sense is that a healthy weight for me is around 170lbs.
I run short distances 2-3x / week, walk/hike probably 10 miles / week, and do light body weights 2-3x / week. My diet is very poor - I eat a lot of carbs and have a major sweet tooth.
After taking semaglutide for 3 months consecutively, I will weigh myself. If I weigh 20lbs less than when I started the semaglutide, this market resolves Yes. If I weigh more, the market resolves No. If I do not take semaglutide for 3 months straight for whatever reason within 1 year from now, I will [try] to resolve this market N/A.
If you were thinking about stacking, I recently had ChatGPT rank weightloss supplements and Rxs in order of effectiveness for another reason (not a doctor, not medical advice). There are probably better lists like this out there, but I don’t think I’ve seen one before.
1. GLP-1 Agonists (e.g., Liraglutide, Semaglutide)
• Mechanism: Mimics the incretin hormone GLP-1, increasing insulin secretion, decreasing glucagon secretion, slowing gastric emptying, and increasing satiety.
• Evidence: Numerous large-scale clinical trials have demonstrated significant weight loss in patients with obesity and type 2 diabetes .
• Sources: Prescription medications like Saxenda (liraglutide) and Wegovy (semaglutide).
2. Bupropion/Naltrexone (Contrave)
• Mechanism: Bupropion is an antidepressant and smoking cessation aid, while naltrexone is used for alcohol and opioid dependence. Together, they reduce appetite and control cravings.
• Evidence: Clinical trials show this combination can lead to significant weight loss
• Sources: Prescription medication (Contrave).
3. Caffeine
• Mechanism: Increases metabolism and fat oxidation.
• Evidence: Numerous studies show caffeine can boost short-term fat loss by enhancing energy expenditure and mobilizing fats from tissues.
• Sources: Coffee, tea, and many fat loss supplements.
4. Green Tea Extract
• Mechanism: Contains catechins, particularly EGCG, which increase fat oxidation and thermogenesis.
• Evidence: Multiple studies support its effectiveness in enhancing fat loss, especially when combined with caffeine.
• Sources: Green tea, supplements.
5. Phentermine
• Mechanism: Appetite suppressant that affects the central nervous system.
• Evidence: Approved for short-term use (up to 12 weeks) in conjunction with diet and exercise. Studies show significant weight loss in the short term .
• Sources: Prescription medication (e.g., Adipex-P, Lomaira).
6. Topiramate (Qsymia)
• Mechanism: Originally used to treat seizures and migraines, it also affects appetite and satiety.
• Evidence: Often combined with phentermine (brand name Qsymia). Clinical trials demonstrate significant weight loss over extended periods .
• Sources: Prescription medication (Qsymia).
7. Dexedrine, Vyvanse, and Adderall (Amphetamines)
• Mechanism: Stimulants that increase norepinephrine and dopamine levels, leading to appetite suppression and increased energy expenditure.
• Evidence: Studies show significant weight loss in patients using these medications for ADHD, though they are not primarily prescribed for weight loss .
• Sources: Prescription medications (Dexedrine, Vyvanse, Adderall).
8. Protein Supplements
• Mechanism: Increases satiety, helps preserve muscle mass, and boosts metabolism.
• Evidence: High-protein diets are consistently linked to better fat loss outcomes and improved body composition.
• Sources: Whey protein, casein, soy protein.
9. Metformin
• Mechanism: Improves insulin sensitivity, reduces hepatic glucose production, and can promote modest weight loss.
• Evidence: Widely used in type 2 diabetes management, with evidence showing modest weight loss benefits in overweight and obese individuals .
• Sources: Prescription medication.
10. Fucoxanthin
• Mechanism: Enhances expression of mitochondrial uncoupling protein 1 (UCP1) in white adipose tissue, promoting fat oxidation and energy expenditure.
• Evidence: Recent human studies have shown significant weight loss and improvements in metabolic markers, particularly when combined with other compounds like pomegranate seed oil .
• Sources: Brown seaweed, supplements.
11. Orlistat
• Mechanism: Inhibits the absorption of fats in the intestine.
• Evidence: Proven to aid weight loss when used alongside a calorie-restricted diet.
• Sources: Prescription (Xenical) and over-the-counter (Alli) medication.
12. Conjugated Linoleic Acid (CLA)
• Mechanism: May reduce body fat by altering the metabolism of fat cells.
• Evidence: Mixed results, but some studies show modest fat loss benefits.
• Sources: Meat, dairy, supplements.
13. Glucomannan
• Mechanism: A soluble fiber that expands in the stomach, promoting a feeling of fullness.
• Evidence: Studies show that glucomannan can aid weight loss when taken before meals by reducing appetite and calorie intake.
• Sources: Konjac root, supplements.
14. Testosterone Replacement Therapy (TRT)
• Mechanism: Increases muscle mass, reduces fat mass, and enhances metabolic rate.
• Evidence: TRT can help reduce fat mass and improve body composition in men with low testosterone levels .
• Sources: Prescription therapy.
15. Hormone Replacement Therapy (HRT) for Women
• Mechanism: Estrogen helps regulate metabolism, insulin sensitivity, and fat distribution, reducing abdominal fat accumulation during menopause.
• Evidence: HRT can help mitigate weight gain and improve body composition in postmenopausal women .
• Sources: Prescription therapy.
16. Yohimbine
• Mechanism: Acts as an alpha-2 adrenergic receptor antagonist, increasing norepinephrine release and fat breakdown.
• Evidence: Some studies suggest modest benefits for weight loss, particularly in stubborn fat areas, though evidence is mixed and side effects can be significant .
• Sources: Supplements.
17. Garcinia Cambogia
• Mechanism: Contains hydroxycitric acid (HCA), which may inhibit fat-producing enzymes and increase serotonin levels.
• Evidence: Mixed results with some studies showing moderate weight loss benefits.
• Sources: Garcinia Cambogia fruit, supplements.
18. Rapamycin
• Mechanism: Inhibits mTOR, a protein that regulates cell growth, proliferation, and survival; associated with lifespan extension and reduced fat mass in animal studies.
• Evidence: Limited human data, but animal studies show promising results for fat reduction and healthspan improvement .
• Sources: Prescription medication, primarily used for immunosuppression.
19. Chromium Picolinate
• Mechanism: Helps regulate blood sugar levels and may reduce appetite and cravings.
• Evidence: Mixed results, with some studies suggesting modest weight loss benefits and others showing minimal effects .
• Sources: Dietary supplement.
20. Probiotics
• Mechanism: May influence gut microbiota, which can affect weight regulation and metabolic health.
• Evidence: Some studies show promising results in terms of weight loss and reduction of body fat, but more research is needed .
• Sources: Supplements, fermented foods.
21. Berberine
• Mechanism: An alkaloid that can improve insulin sensitivity and has anti-inflammatory effects.
• Evidence: Some studies suggest it can help with weight loss and improve metabolic health markers .
• Sources: Supplements.
22. Capsaicin
• Mechanism: Found in chili peppers, it can increase metabolism and promote fat oxidation.
• Evidence: Studies show it can aid in weight management by boosting metabolic rate and reducing appetite
The annoying thing about weight loss supplements in my experience is that they fall into 3 categories:
1. Legal but barely effective
2. Illegal and/or slightly harmful but effective
3. Illegal and very harmful but very effective
Semaglutide is a legal and effective one, which makes it so amazing.
Also, most supplements either
- Increase metabolism
- Decrease appetite
or
- Try to change absorption of food
Issue here is that the first two mostly happen by taking stimulants (coffee, nicotine, amphetamines, ephedrine) which is not always good for you (but maybe better than obesity).
In particular ephedrine is often used by bodybuilders in the so called "ACE" stack.
But sadly ephedrine is a controlled substance in most parts of the world (afaik because you can easily use it to cook more dangerous drugs)
For the third category (very harmful) there are things like DNP, which also increases your energy expenditure. Not as a stimulant, but by destroying the function of you mitochondria. Also sometimes used by bodybuilders, which to me seems crazy. It was made illegal in germany after a teenage girl accidentally over-dosed.
All other substances have rather negligible effects on weight loss iirc.
Examine.com has amazing write-ups on this too, focusing on supplements.
I had a max BMI of 41, clinically obese, and was prescribed a few medications at different times to encourage weight loss. From my experience, you can’t sustainably lose more than .5 kg/1 pound per week without changing your habits.
In that regard, I’d say your diet is more impactful than physical activity. For many months I had 10-15 hours of light outdoor activity per week, plus moderate-intense workouts 1 or 2 days a week, but did not lose nor gain weight. By calories alone, swapping an ounce bag of Lay’s chips for one cup of strawberries is the same as running a mile. You’d need to walk over an hour to burn off a small Wendy’s Frosty.
I haven’t tried semaglutide specifically, but I doubt you’ll lose much weight using it without changing anything else.
I think this is realistically <10%. but I haven't bet it that far because of time value of money and also some risk aversion. Semaglutide works, but it's not this fast for most people, especially not for people like OP who are not extremely obese.
So it's about 13 weeks of semaglutide. Assuming you start at low dose then increase.
You won't be losing more than 1lb per week in the first 4 weeks. Assuming you increase dose successfully, you'd need to lose 16lb in 9 weeks. That's just under 2lb every week.
It's possible but is at the right tail of distribution of semaglutide studies.
If you hold willingness to exercise constant (or maybe higher if he’s motivated) and then add semaglutide, I think you’ll see more weight loss as you’ll have two mechanisms by which he’s losing weight rather than one where it’s maintaining “homeostasis.” In addition weightloss from decreasing appetite, my model says this would also enable the exercise to be more effective (if he can continue it).
Can you give us some more info about your eating habits? Do you know approximately how many calories you eat per day on average in a typical week? How many meals do you eat per day and how large is the largest meal, usually? Do you occasionally eat meals (in the loose sense; a day of prolonged overeating could also count) much larger than this, such that the meal might significantly detract from weight loss efforts? Roughly how many calories do you get from processed foods? How many calories from liquids?
My typical day looks like:
Bagel / eggo / Starbucks sandwich for breakfast / huel
Frozen gnocchi from Trader Joes / other freezer meal / sandwich for lunch
Hello Fresh / Indian/Thai takeout for dinner
Snacking on almonds / peanut butter cups / sour candy / baked goods / fruits during day
Dinner is largest meal. I do occasionally overeat such that I've had significantly more during a day than I typically do. Probably 50%+ of my calories are from processed foods (total estimate).
I've never tracked calories and have no idea how much I eat per day.