The GLP-1 Era: Why Muscle and Mental Health Have Become Primary Care Responsibilities

FUNDED EDUCATIONAL CONTENT BY WILEY

This funded, non-CME educational content was developed by Wiley with funding from BTL Industries, Inc. to provide convenient access to information that may be of interest. It should not be considered an AAFP or American Family Physician endorsement or recommendation of the funder’s products, services, policies, or procedures. Journal editors were not involved in the development of the content.

GLP-1 receptor agonists represent one of the most consequential advances in obesity and metabolic medicine in decades, delivering meaningful weight reduction, improved glycemic control, and cardiometabolic benefit across diverse patient populations.¹ Yet the success story is more complicated than the headlines suggest. Primary care physicians increasingly encounter downstream consequences among their patients, such as persistent fatigue, loss of lean muscle mass, emotional flattening, and high discontinuation rates.^2,3

The problem intensifies in patients older than 50. Adults entering GLP-1 therapy against a backdrop of hormonal decline, i.e., women in menopause and men in andropause, face compounded vulnerability. Rapid pharmacologic weight loss can unmask sarcopenic and mood-related vulnerabilities that traditional obesity management has never encountered.^4,5

The behavioral and emotional dimensions of GLP-1 therapy land squarely in primary care. Depression diagnosis and management originate in family practice at high rates, with primary care physicians serving as principal treatment providers for the large majority of patients with mood disorders.^6–8 Psychiatry wait times in many markets can stretch for months, and medication stacking remains a common workaround with its own risks in older patients.^9,10 “This is an area of our medical system that is a big letdown—mental health coverage is very poor or non-existent. In my area, it can take four to six months to see a psychiatrist,” says Bradley Perkins, MD, with Transform Wellness in Los Gatos, Calif.

When mental wellbeing determines adherence and behavioral change, outsourcing that dimension of care to an overwhelmed specialty system is not a sustainable strategy. Neuromodulation technologies are emerging as adjunctive tools supporting behavioral health within the primary care environment. These are non-pharmacologic, workflow compatible, and capable of addressing the cognitive and emotional underpinnings of behavior change without adding to medication burden.

Skeletal muscle is a primary metabolic organ. It regulates glucose disposal and insulin sensitivity, supports bone density through mechanical loading, and constitutes the principal reserve against frailty.¹¹ When GLP-1–driven weight loss depletes lean tissue alongside fat, the downstream consequences are clinical, not cosmetic. Georgine Nanos, MD, MPH, with Kind Health Group in Encinitas, Calif., takes it a step further: “In the GLP-1 era, muscle preservation may be the most underrecognized preventive intervention available to primary care,” she says.

Some analyses raise concern about sarcopenia acceleration in older adults, postmenopausal women, and those with low baseline muscle mass.^4,5,12 Hip fracture mortality approaches 20% among older women within the first year following fracture, adds Dr. Nanos, citing Cummings and Melton.¹³

High-intensity focused electromagnetic (HIFEM) technology combined with synchronized radiofrequency has demonstrated clinically relevant results in this context. In a multicenter MRI evaluation study, simultaneous application produced a 25% increase in muscle mass.¹⁴ This directly counteracts lean tissue depletion that accompanies aggressive GLP-1–induced weight loss, with outcomes supported by MRI-confirmed evidence.^15–17

GLP-1 therapy modifies satiety signaling. What it does not reliably restore is the cognitive and emotional architecture that governs food behavior over time. Executive function, reward circuitry, and stress regulation determine whether a patient can sustain behavioral change when pharmacologic appetite suppression is removed.^18–20 As Dr. Perkins explains, “If someone is struggling with stress, depression, anxiety, it is hard to make good choices. We tend to go to comfort foods or do things that are going to stimulate our dopamine (which is usually sugar or alcohol). This becomes a slippery slope … with low dopamine, they crave foods and have low motivation, which leads to apathy and worsening executive function.”

Emerging evidence supports neuromodulation as an adjunct in this space. A systematic review found measurable effects on executive function and food desires in individuals with obesity following neuromodulation interventions, e.g., transcranial magnetic stimulation (TMS).²¹ The Exomind device (BTL Industries, Marlborough, MA, USA) is built on the foundation of TMS. The technology stimulates areas of the brain involved in emotional regulation, cognitive function, and self-control. Recent clinical comparisons of TMS with semaglutide and SGLT2 inhibitors suggest complementary rather than competing mechanisms.²² Supporting cognitive resilience may meaningfully influence long-term metabolic durability.

A persistent barrier to uptake of muscle-strengthening technologies in primary care is their historical association with cosmetic outcomes. That framing no longer applies. For example, FDA clearance for high-intensity focused electromagnetic (HIFEM)-based devices now includes treating medical diseases and conditions.²³ Emsculpt Neo (BTL Industries, Marlborough, MA, USA) is a non-invasive treatment that combines HIFEM technology and radiofrequency for muscle building and strengthening. Functional muscle strengthening applied to patients recovering from illness-related deconditioning, menopausal muscle decline, or injury aligns with fall reduction and mobility preservation goals that primary care physicians already own.^15,17,24

The conventional referral pathway for a GLP-1 patient presenting with mood changes, muscle loss, and deconditioning fragments care across multiple providers, i.e., psychiatry, physical therapy, and other specialties. Each step adds friction and each handoff creates an opportunity for disengagement. Referral fragmentation is a recognized driver of poor follow-through and lost continuity in primary care management of chronic conditions.²⁵ Dr. Perkins agrees, saying, “We are the quarterback of their care; our patients trust us, and if we can provide all of these services, the better. With fragmented care, it can delay care by months when trying to refer to a mental health provider.”

Collaborative care models that deliver behavioral health support within primary care have demonstrated effectiveness for depression management.²⁶ Integrated technologies allow physicians to address interconnected physical and behavioral health concerns without disrupting continuity. Hands-free treatment models supervised by trained staff without continuous physician presence allow practices managing high volumes of GLP-1 patients to expand services without proportionally increasing physician workload.^27,28

The GLP-1 era has changed what patients bring to primary care. “The emerging responsibility of primary care in the GLP-1 era is ensuring that metabolic improvement does not come at the expense of muscle integrity, mobility, or mental resilience," says Dr. Nanos. Many patients arrive having lost weight but feeling depleted, weaker, emotionally flattened, and uncertain whether to continue. These are not transient side effects. They are signals of physiological transformation that appetite suppression alone cannot manage. “The future of family medicine may not depend on prescribing more medication, but on restoring function—physically and mentally—within the same trusted clinical relationship,” she adds.

Muscle preservation, cognitive support, and behavioral resilience are not adjuncts to GLP-1 management. They are its necessary complement.