Ozempic and Wegovy - Effortless fat loss or Ticking time bombs?
The (initial) results are in from various studies and a recent review which followed nearly 2,000,000 individuals for between 2 and 5 years:
GLP-1 receptor agonists such as semaglutide(Ozempic, Wegovy) and tirzepatide(Mounjaro) - were originally designed to lower blood sugar in diabetics, but one of the side effects of using these drugs was a profound lowering of appetite, which in turn led to substantial weight loss.
TL;DR
GLP-1RAs certainly seem to be wonder drugs when it comes to weight loss for the obese or overweight, however they do not come without risks. Patients taking these drugs should keep a close eye on their hormone levels, lean body mass loss (resistance training should probably be undertaken for the duration of treatment to help mitigate muscle and bone loss), their mental health and of course their digestive system. Although they come with the risk of side effects it would appear for the time being that the positive effects outweigh the negative for those with substantial amounts of fat to lose and for whom traditional methods of fat loss have failed or are unworkable.
Weight Loss
Some studies have shown GLP-1RAs achieving as much as 30% weight loss from baseline [13], with other studies showing weight loss of up to 15% of body mass with a substantial amount of test subjects achieving, and subsequently maintaining, weight loss of 5 - 10% of body mass. [15]
Appetite suppression
In addition to curbing eating further studies have shown they also seem to reduce users’ desire to drink alcohol[4][3], smoke cigarettes[3], gamble[3], shop compulsively[3] and use cannabis[2] - it would appear they reduce appetites across the board. [1] This is possibly due to their ability to mitigate the rewarding properties of alcohol and other addictive drugs. [13]
Health risk reductions
Some studies suggest GLP-1 receptor agonists reduce the risk of heart attacks, stroke, heart failure, high blood pressure and Alzheimer’s. [4]
Bone Health
Some studies have shown that GLP-1RAs can enhance bone density and improve bone quality. [7] [8] Other studies have shown GLP-1RAs lowered bone density over the course of a year of treatment. [14] The overall data indicates that GLP-1RAs have a neutral impact on bone health and do not appear to increase bone breaks or fractures. [6]
Digestive System Health
GLP-1RA use was associated with an increased risk of abdominal pain, nausea and vomiting, GERD (acid reflux/heartburn), gastritis, gastroparesis, diverticulosis and diverticulitis. [13] It would seem prudent to closely monitor those taking GLP-1RAs, especially at high doses, for gastrointestinal adverse events.[5]
Lean Mass Loss
GLP-1 receptor agonists may cause substantial muscle loss. Studies suggest muscle loss with these medications (as indicated by decreases in fat-free mass) ranges from 25% to 39% of the total weight lost[11] with some studies suggesting as much as 60% of the weight lost could be lean mass.[12] Lean mass reductions of this scale seem concerning, but changes in lean mass may not be fully attributable to reductions in muscle mass as the lean mass lost includes mass lost from organs, bone, fluids, and water from fat tissue. [12]
Hormonal Effects
GLP-1RAs appear to have a negative impact on the endocrine system of some users - males using semaglutide were significantly more likely to be subsequently diagnosed with ED(Erectile Dysfunction), and males with a prescription for semaglutide were more likely to receive a subsequent diagnosis of testosterone deficiency. [9]
Mental Health
Initial reports raised concerns about suicidal thoughts and self-injury among GLP-1RA users[10], however, later studies have not replicated these results and in fact have shown the opposite where GLP-1RA drug use was shown to reduce these risks.[1][13] A 2023 review of GLP-1RA use by the European Medicines Agency found no evidence of a causal link between GLP-1RA use and the risk of suicidal ideation, attempt or intentional self-harm.
Cardiovascular Health
GLP-1RAs were associated with reduced risk of major adverse cardiovascular events (MACE) including heart failure and stroke and major adverse kidney events (MAKE) including acute kidney injury and chronic kidney disease.[13] Studies have also shown consistent associations between GLP-1RAs and the blood coagulation system, with a reduced risk of deep vein thrombosis, pulmonary embolism and post-thrombotic sequelae, including pulmonary hypertension.[13]
Side Effects
GLP-1RAs increased the risk of hypotension (low blood pressure) and syncope (fainting) and suggest that careful monitoring of blood pressure (and adjustment of antihypertensive medications) in patients on GLP-1RA may be required. [13] Other side effects noted were sleep disturbances, headaches, joint pain and arthritic disorders, nephrolithiasis(kidney stones), interstitial nephritis(kidney inflammation) and drug-induced pancreatitis.[13]
Conclusion
All medication comes with the risk of side effects and GLP-1RAs are no exception. Multiple side effects are noted above and anyone taking these drugs for weight loss should be aware of the potential side effects and monitor themselves so as to catch any adverse effects before they become problematic. The main effects which should be monitored in my opinion would be unwanted lean mass loss (muscle or bone loss), hormonal changes (in the case of men taking these drugs - women do not seem to be as affected here). Obviously gastric problems and mental health problems should be monitored but these are more obvious in their presentation, so should be easier to spot. For the time being, with the evidence we so far have to work with it would appear that the positive effects outweigh the negative for those with substantial amounts of fat to lose and for whom traditional methods of fat loss have failed or are unworkable. The bottom line, as always - Caveat Emptor.
[1] https://pubmed.ncbi.nlm.nih.gov/37499675/
[2] https://www.nature.com/articles/s41380-024-02498-5
[3] https://www.mdpi.com/2076-3425/14/6/617
[4] https://doi.org/10.1038/s41598-023-48267-2
[5] https://www.bmj.com/content/384/bmj-2023-076410
[6] https://pmc.ncbi.nlm.nih.gov/articles/PMC8878541/
[7] https://pmc.ncbi.nlm.nih.gov/articles/PMC8243369/
[8] https://pmc.ncbi.nlm.nih.gov/articles/PMC5413504/
[9] https://academic.oup.com/jsm/article/21/Supplement_1/qdae001.148/7600659?
[10] https://www.nature.com/articles/s41598-024-75965-2
[11] https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00272-9/abstract
[12] https://pubmed.ncbi.nlm.nih.gov/38937282/
[13] https://pubmed.ncbi.nlm.nih.gov/39833406/
[14] https://pubmed.ncbi.nlm.nih.gov/38737002/
[15] https://pmc.ncbi.nlm.nih.gov/articles/PMC8189979/ \