TRT, GLP-1s, and peptides: How to counsel patients stacking longevity therapies

The convergence of patient-driven interest in testosterone replacement therapy, GLP-1 receptor agonists, peptides, and longevity optimization is fundamentally changing what patients bring into the exam room — and creating a new clinical responsibility to distinguish evidence-based benefit from marketing-driven expectation, according to Jean Cunningham, PharmD, BCPS, senior director of Medical Affairs for Empower Pharmacy.

Cunningham described TRT as one of the most conversation-generating therapies in the current landscape, driven by patients who notice tangible early effects and then seek broader applications.

"Clinicians can serve a very important role to help individuals understand—here's what we can confidently say based on the evidence, and here's where that might be marketing and those expectations might be a little too high," she said. The established indications and evidence base for TRT are well-characterized; the emerging interest in using it as a health optimization tool in broader populations requires a more nuanced evidentiary conversation.

When patients present wanting to combine TRT with GLP-1 receptor agonists—a common stacking request—Cunningham recommended a specific baseline assessment before adding any new agent. She advised ordering a DEXA scan at the outset, because GLP-1 therapy is associated with reductions in nutrient intake, strength, and bone density that can be meaningfully counteracted by TRT and structured resistance training—but only if those changes are being measured.

"One to two pounds a week with a GLP-1, strength training, and maybe adding in TRT—you should be noticing that muscle loss is not occurring," she said. "But how are you measuring that? How are you observing those changes?" The DEXA scan provides a trackable baseline against which to evaluate whether the combined regimen is achieving its intended effect on body composition.

Peptide therapy represents the frontier where patient enthusiasm most often outpaces the evidence. Cunningham noted that patients increasingly arrive having researched specific agents through medical influencers or peer networks, and they expect their provider to be conversant not only with FDA-approved peptides but with the growing list of agents under regulatory consideration and those already circulating outside formal approval pathways.

"Providers need to be versed in how they can communicate to patients about safety, risk, or quality concerns," she said, while also staying genuinely curious about what patients are trying to accomplish.

"When you start peeling back those layers, you start finding out more about what their goals are and what is at the root of their want to improve their health."

The clinical framework she described operates across three tiers: therapies with established evidence of benefit, emerging therapies with plausible mechanisms but limited human data, and agents where risk signals outweigh theoretical benefit. Helping patients locate each therapy they're asking about within that framework—without shutting down the conversation—is increasingly part of the role clinicians are being asked to play.

"Providers are expected to know what's in the evidence and what's in this emerging field," Cunningham said.