OB=obesity; T2D=Type 2 diabetes; n=population sample

As we can see from the graph above, incretin-based weight loss pharmacotherapy achieves ∼15–24% reductions in body weight. However, an important but often overlooked factor in incretin studies relates to the type of weight lost. When looking at “type” of weight lost it is important to consider whether it is fat-mass (FM) or fat-free mass (FFM), also commonly called lean mass (LM). Fat free mass or lean mass is often considered skeletal muscle, which naturally is lost with age. 

Jastreboff et al, evaluating Tirzepatide (a GLP-1) found that a sequential dose (from 5 mg to 10 mg to 20 mg/once weekly over 72 weeks) produced an average weight loss of 20.6 kg (19.6%) at 72 weeks evaluation. Of this, the change in fat mass was 17 kg (33% of weight lost) and the change in lean mass was 6 kg (10.9% of weight lost). The loss of 6 kg LM likely underestimates the loss of LM at higher doses of Tz and in more responsive individuals. This is a profound level of muscle loss. It is possible that the loss of LM parallels the loss of fat and reduction in overall weight, reflecting the dosage and reaching a plateau after extended durations of treatment. It is not known whether a slower dose titration of these medications to bring about slower weight loss would cause less loss of lean muscle.

Why does muscle mass matter? 

The development of obesity is affected by the quantity and quality of muscle mass and its metabolic rate (in other words, the energy burned at rest to keep a system going). Evidence indicates that excess adipose (fat) tissue impairs muscle recruitment and activation (an important feature for postural strength and control). Adipose tissue also affects the energy burned at rest (aka resting metabolic rate). In short, more energy is burned at rest with higher amounts of muscle tissue. This is really important to consider as we age since higher amounts of muscle mass means healthier body composition.

For some perspective, there is a natural loss of lean mass that occurs with age (also known as sarcopenia) and increases significantly when a woman enters menopause. Sarcopenia is something we want to curb, especially as we age since it increases the risk of cardiovascular disease, reduces bone health, impairs metabolism, creates frailty and from a musculoskeletal perspective, perpetuates musculoskeletal pain. 

While greater incretin-induced body weight reduction induces larger improvements in HbA1c, triglycerides, ALT, waist circumference, and blood pressure, it remains unclear whether loss in LM has detrimental long-term impacts on cardiovascular risk factors or its total effect on the musculoskeletal system. 

To place the relevance of these differences in context, aging-related reduction in LM in older individuals ranges from 1 to 3 kg per decade, depending upon age and other factors. Lean mass loss is related to loss of strength and function in humans. Studies indicate that, from the third to fourth decade onwards, aging is accompanied by loss of strength of around 2.5–4.0% per year (73). Why does this matter? It can be estimated that loss of 6 kg LM associated with incretin therapies approximates the impact of a decade or more of human ageing on skeletal muscle mass 

In general, to fight the loss of lean muscle mass, one can add resistance training and a high protein diet. One study showed that diet and resistance training lessened the loss of LM by 93.5%. Doing supervised resistance training interventions with a duration above 10 weeks, a frequency of up to 2–3 times/week, an intensity range between 50 and 80% of 1 repetition maximum, and a minimum of seven exercises/session (e.g., large muscle groups) elicit improvements in LM acquisition and/or maintenance in aging men and women, with an average increase of approximately 1.1 kg.

How does this clinical picture relate to Physical Therapy at The Perfect Squat?

We just learned that prolonged use of a GLP-1 does lead to weight loss and a significant percentage of that is lean muscle mass. We also learned that as we age we naturally lose lean muscle mass. Given that we see adult clients who are approaching if not over the age of 40, the majority of our clients are experiencing a loss of lean muscle mass. If you are also on a GLP-1, then your risk of lean mass loss is even greater. We also learned above that resistance training (weight lifting) and a protein rich diet can help decrease the dramatic loss of lean muscle mass as we age. 

Now for the physical therapy part. In “physical therapy speak”, pain and function are two different things. To address one implies addressing the other. To overcome pain originating from the musculoskeletal system it is very helpful if there is baseline conditioning. In the absence of this base fitness, it must be built first (even if uncomfortable!) before the movement dysfunction causing the pain is addressed. Functional fitness is our focus knowing that as we improve one (function) we are improving the other (pain). 

Here at the Perfect Squat we use a three step process to achieve health and wellness. 

• Step 1: Recover from pain and limitations

• Step 2: Rebuild proper mechanics and address root cause

• Step 3: Redefine future performance and prevent recurrence

Clearly, physical therapy alone is insufficient to reverse effects listed above. It must be combined with a lifestyle change of a healthy well balanced diet and exercise, which always works best in the midst of solid social support. Our specialty is helping you get the know-how and movements properly loaded to fight those effects of aging (and GLP-1s if that’s your case). So, yes, it matters that your physical therapist be aware of your intake of GLP-1s, as is true that they are aware of your full medical history, so that they can prescribe the correct dosage, target specific movements, and give you truly personalized and effective care.