There is so much hype regarding the newest weight loss drugs such as Ozempic, Wegovy and Zepbound and others otherwise known as GLP 1 inhibitors. The generic names are semiglutide, tirzepatide, liraglutide, dulaglutide and others. The demand for the GLP1 inhibitors and others has far outstripped the supply. 

People are using them for short term weight loss for cosmetic reasons and the people that need them the most can’t get them or can’t afford them. They are costly and the treatment is for life unless you want to regain the weight. There are clear indications for the use of these drugs, however they come at a price.

Weight Loss

Is the amount of weight loss all that it hyped up to be? In some cases, yes. It is reported that people can lose 20% of their weight. Some don’t lose any and some hit a plateau and there is nothing left to do.

The tricky part of this is that weight loss is reported in percentage of body weight, not pounds and the definition of success is as follows:

According to FDA Guidance for Industry Developing Products for Weight Management, the criteria for success is after 1 year of treatment, is at least 5% more weight loss than the placebo group or, 35% of subjects who lost ≥ 5% of baseline body is double the proportion in the placebo group.1 Therefore a 200 pound person would lose 10 more pounds than someone who was in the placebo group.

Average weight loss in most studies is reported as 7.9% body weight or 15.6 pounds. 2 Weight loss will hit a plateau and if you stop the medication, you will gain back 80% of what you lost.

For example, a 200-pound man would be expected to lose 15.8 pounds. Weight loss is not sustainable, and you would have to be on a very expensive drug for life.

• The average cost of about $1,000 a month for 12 months is $12,000 for a year. For a weight loss of 15.6 pounds. The cost is about $769 per pound lost!

Loss of Muscle

Loss of muscle mass is associated with an increased risk for osteopenia and osteoporosis, fatigue, injuries, and decreased strength. In addition, muscle is what burns calories and losing muscle will change your metabolism for the worse.

You can be what is called “Skinny Fat.” Even if you look thin, you may have a body composition that is not healthy because of a high percentage of fat and a low percentage of muscle. The medical term for someone who’s lean but has a metabolic profile that puts them at risk of developing metabolic disease is a “metabolically obese, normal weight” individual.

For example, a 200 pound person

200 pounds with 30% body fat and 70% muscle will have the same BMI and weight as someone who weighs 200 pounds with 50% body fat and 70% muscle weight. The body composition of the person with only 50% muscle weight will most likely have metabolic issues such as high cholesterol, high blood pressure and insulin resistance. It will be harder for them to lose weight.

The STEP 1 and SUSTAIN 8 of semaglutide trials found 39–40% of weight lost on the GLP-1 drugs was lean mass otherwise known as muscle mass. A 2021 meta-analysis of 18 randomized controlled studies showed significant drops in fat-free mass (muscle) with GLP-1 drugs. Data from the SURMOUNT-1 tirzepatide study reached more positive conclusions, concluding that fat mass dropped between 33% and 36% and lean mass by 10% to 11%, depending on the age group. In other words, roughly one-quarter of the weight lost in that study was lean mass. For context, some degree of lean muscle mass loss is normal in most weight loss scenarios, as the body tends to shed both fat and some lean tissue when losing weight.3

Side Effects

Side effects are frequent, and some can be quite serious. Most are gastrointestinal consisting of nausea, vomiting, and diarrhea severe enough to discontinue treatment. Most resolve as time goes on. 4

Other side effects include:4

• Loss of appetite
• Aversion to food
• Malnutrition
• Pancreatitis
• Gallstones
• Increased Heart rate
• Allergic reactions
• Upper respiratory tract infections
• Headache
• Acute kidney injury

Wrinkles, sagging skin on face and appearing older5

Benefits

People with diabetes, obesity and risk factors for cardiovascular diseases can benefit the most from these drugs.

Cardiovascular and Metabolic Benefits include:6

• Lower cholesterol, triglycerides, LDL cholesterol
• Lower ALT liver functions
• Weight loss
• Lower hemoglobin A1C levels – a marker for diabetes

Alternatives

These drugs are effective for the right population; however, weight loss and cardiovascular benefits can be achieved in other ways. Participants in the Metabolic Reset Diet and the Group Metabolic Reset diet have reported an average of ½ pound a day for a 40 day program for women and 1 pound a day for men. Average weight loss may be equal to or superior to these drugs and it is only 40 days as opposed to a lifetime. 

Before jumping on the weight loss bandwagon with unknown long term effects such as heart valve problems found to occur with Phen-fen, try an alternative such as the Metabolic Reset Program or the Group Metabolic Reset Program that is far more cost effective with transient side effects such as headache and fatigue for a few days. 

1. Jensterle M, Rizzo M, Haluzík M, Janež A. Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review. Adv Ther. 2022;39(6):2452-2467. doi:10.1007/s12325-022-02153-x
2. Rubino D, Abrahamsson N, Davies M, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity. JAMA. 2021;325(14):1-12. doi:10.1001/jama.2021.3224
3. Buntz B. Semaglutide and GLP-1: Effects on lean body mass still unclear. Drug Discovery and Development. Published November 27, 2023. Accessed March 16, 2024. https://www.drugdiscoverytrends.com/glp-1-impact-lean-mass/
4. Filippatos TD, Panagiotopoulou TV, Elisaf MS. Adverse Effects of GLP-1 Receptor Agonists. Rev Diabet Stud RDS. 2014;11(3):202-230. doi:10.1900/RDS.2014.11.202
5. Humphrey CD, Lawrence AC. Implications of Ozempic and Other Semaglutide Medications for Facial Plastic Surgeons. Facial Plast Surg FPS. 2023;39(6):719-721. doi:10.1055/a-2148-6321

6. Uneda K, Kawai Y, Yamada T, et al. Systematic review and meta-analysis for prevention of cardiovascular complications using GLP-1 receptor agonists and SGLT-2 inhibitors in obese diabetic patients. Sci Rep. 2021;11(1):10166. doi:10.1038/s41598-021-89620-7