The Benefits
The data from clinical trails such as SUSTAIN and STEP, show a reduction of overall body weight on average of 10–15% and improvement in cardiovascular and metabolic health markers such as blood pressure, inflammation, liver fat, and improving heart and kidney outcomes.
Unfortunately, what these trials fail to assess is what was actually lost—body fat or muscle mass. When you look deeper into the data, you’ll find that many patients lost a significant amount of muscle mass.This happens due to, the rapid reduction of calorie and protein intake and lack of exercise, especially resistance training. Additionally, there may be a hormonal effects of GLP-1 drugs, leading to blunting the anabolic pathways (muscle-building). In other words, if you’re eating much less on a poor-quality diet, and not engaging in weight-bearing exercise, you will lose muscle.
Here is the Evidence of What Was Lost
Lean body mass accounts for 20–32% of the weight lost. A 2019 systematic review of GLP‑1 receptor agonists (GLP‑1 RAs, e.g., semaglutide) and SGLT2 inhibitors in humans found that 20–50% of total weight loss came from lean body mass (LBM) across over half of the studies examined (1 )
Older adults are at much higher risk. Experts warn that older people who are already prone to muscle loss (sarcopenia ) should be extra cautious as the muscle loss in this population is even higher. The weight loss drugs are believed to be responsible for accelerating 20 years’ worth of age-related muscle loss in about 16 months. Protein intake and resistance training are essential mitigation strategies to prevent muscle loss (2)
Gastrointestinal Issues
The weight loss drugs are known for slowing down your digestions and absorption therefore leading to gastroparesis (paralyzed stomach), dehydration, constipation and pancreatitis.(3)
Weight Regain
In the study by Wilding et al., The Lancet Diabetes & Endocrinology, 2022, patients who discontinued semaglutide regained approximately two-thirds of their lost weight within one year. However, a critical question remains unanswered: what kind of tissue was regained—was it primarily fat, or was muscle mass restored? Notably, the same group of patients experienced a worsening of cardiometabolic markers, including blood pressure, cholesterol, and glucose levels.¹This raises an important clinical consideration: if weight regain is accompanied by deteriorating health markers, does this suggest that long-term—perhaps even lifelong—use of the medication is necessary to sustain the benefits?It is especially important to ask: what exactly comes back during weight regain? Is it the lean muscle mass patients need, or is it primarily fat, which contributes to metabolic dysfunction? The answer remains unclear, as data on body composition in long-term discontinuation studies are limited.
Thyroid Cancer
In earlier laboratory studies, researchers noticed an increased incidence of a specific type of thyroid cancer called medullary thyroid cancer. This lead to FDA to mandate a boxed warning on the following drugs Rybelsus as well as Ozempic and Wegovy.
Pancreatitis
Pancreatitis is inflammation of the pancreas. There are several case reports where patients were hospitalized with elevated pancreatic enzymes and after the discontinuation of the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) the patients enzymes came back to normal.
Other Warnings Issues By FDA
FDA has requested that Novo Nordisk issues the following warnings on the labels of the semaglutide:
- Hypoglycemia Gall bladder issues Vision
- Increased heart rate
- Depression
- Suicidal thoughts
- Pancreatitis
Bottom Line
Achieving sustainable weight loss is hard work—it requires long-term lifestyle changes. It starts with changing your mindset about eating. If you’ve weighed all the risks of weight loss drugs and still believe they’re a good fit for you, and you want to do it the right way—by preventing muscle loss and avoiding gastrointestinal issues—then know this: you’ll still need to eat well-balanced, high quality, high protein diet (1.6gm/kg), rich in fiber and antioxidants, stay well hydrated, address emotional triggers as meds reduce appetite but not cravings or emotional patterns and engage in weight-bearing activity daily.