GLP-1–based therapies, including glucagon-like peptide-1 receptor agonists (e.g., semaglutide), dual incretin agonists (e.g. tirzepatide), and forthcoming GLP-1–modulating drugs like retatrutide, have rapidly reshaped the clinical management of obesity, type 2 diabetes, and cardiometabolic disease.

In less than a decade, these drugs have moved from the weight management and endocrinology niches to much wider use in primary care, neurology, and hepatology, as well as longevity, integrative, and functional medicine practices, where clinicians are using them for an ever-expanding list of conditions.

Recent estimates suggest that every 1 in 8 Americans has tried a GLP-1 therapy, with that number forecasted to reach 1 in 4 by 2030. That number sounds impressive, but includes the 12% of Americans who are active users, as well as 15% who are lapsed users.

The rapid assimilation of these drugs into every facet of medical and preventative care underscores both the clinical demand and cultural impact of this therapeutic class.

At the same time, the widespread use of drugs that have such powerful impact on human physiology urgently requires awareness and thoughtful consideration of what is still unknown about them.

While randomized trials and real-world data demonstrate a wide range of meaningful benefits from GLP-1 therapies, widespread use has also revealed persistent challenges: gastrointestinal intolerance, fatigue, sarcopenia, micronutrient inadequacy, sudden discontinuation due to side-effects, cost, or loss of access, and what no one wants to think about: high rates of weight regain after cessation.

Rather than positioning GLP-1 medications as either miracle cures or problematic shortcuts, Koff reframes them as one component in an array of approaches we can take to affect the physiologic system that governs appetite, digestion, metabolism, and weight.

Dietitian Ashley Koff’s new book, Your Best Shot: The Personalized System for Optimal Weight Health—GLP-1 Shot or Not, arrives at a pivotal moment in the GLP-1 trend and our understanding of it.

Rather than positioning GLP-1 medications as either miracle cures or problematic shortcuts, Koff reframes them as one component in an array of approaches we can take to affect the physiologic system that governs appetite, digestion, metabolism, and weight. This ecosystem-based approach makes the book particularly relevant for clinicians seeking durable strategies for patients currently using GLP-1 therapies, those tapering off, and those unable or unwilling to use pharmaceuticals.

The Switch Framework

One of the book’s most clinically useful contributions is its conceptual model of appetite and metabolic regulation.

Koff introduces the idea of the “Switch,” a network of peptide hormones including GLP-1, peptide YY (PYY), cholecystokinin (CCK), and glucose-dependent insulinotropic peptide (GIP). As she explains, “Together these activate insulin and the hormones that trigger appetite and satiety. I call them the Switch.” This framing explains why GLP-1 RAs are effective while also clarifying why pharmacologic intervention alone rarely produces durable outcomes.

Koff emphasizes that endogenous GLP-1 signaling is short-lived by design, likening it to a motion detector that turns off quickly. In contrast, GLP-1 agonists act as a prolonged “force field,” remaining active for days. While this extended signaling produces powerful appetite suppression and other metabolic effects, it carries physiologic trade-offs that require careful management.

For clinicians, the Switch framework offers practical language for patient counseling, helping individuals understand that sustainable, healthy weight depends on restoring and supporting the underlying regulatory system rather than relying indefinitely on a single external signal.

GI Side Effects: Mechanism-Based Management

Gastrointestinal adverse effects are among the most common reasons patients stop taking GLP-1 therapies. Koff’s discussion of these symptoms stands out for its mechanistic clarity. She notes that GLP-1 agonists are “always on,” delaying gastric emptying day and night, and reducing time spent in a true parasympathetic “rest and digest” state.

Rather than attributing nausea, bloating, constipation, or early satiety solely to dietary indiscretion, Koff reframes these symptoms as signs of digestive under-resourcing. Throughout multiple patient cases, she demonstrates how targeted interventions—hydration optimization, electrolyte support, supplementation with the right form of magnesium, glutamine supplementation, microbiome support, and meal timing—can significantly reduce the GI side-effect burden.

In one illustrative case, a patient experienced resolution of gas and bloating alongside improved treatment adherence and better functional outcomes, highlighting the value of addressing digestive physiology rather than simply lowering medication dose.

Koff emphasizes that endogenous GLP-1 signaling is short-lived by design, likening it to a motion detector that turns off quickly. In contrast, GLP-1 agonists act as a prolonged “force field,” remaining active for days. While this extended signaling produces powerful appetite suppression… it carries physiologic trade-offs that require careful management.

For clinicians, this approach provides a practical framework for managing side effects without defaulting to discontinuation as soon as a problem arises, while also reinforcing the importance of adequate nutrition in patients whose appetite signals are profoundly altered.

Sarcopenia & Lean Mass Preservation

A major strength of Your Best Shot is its sustained attention to body composition. Koff repeatedly emphasizes that scale weight alone is an insufficient marker of success, particularly in patients using GLP-1 drugs. She describes patients who achieved substantial weight loss only to discover, through DEXA scanning, that in addition to fat loss, they’d also lost muscle and bone mass. This, writes Koff, is “a troubling situation” because it is as a clear risk factor for metabolic decline and post-medication weight regain.

Importantly, Koff moves beyond generic recommendations to “eat more protein.” She details the importance of protein distribution across meals, minimum effective doses per meal, and the risks of excessive protein loading in patients with slowed gastric emptying. She also highlights the role of targeted amino acids, creatine, taurine, and resistance training in preserving lean mass during pharmacologic weight loss.

For clinicians managing older adults, perimenopausal women, or patients with chronic disease, this emphasis on muscle preservation is particularly salient. The book offers practical, actionable guidance that aligns with emerging concerns about sarcopenic obesity and frailty in long-term GLP-1 users.

Longevity Trade-offs

The persistent “on” signaling Koff describes may be the most important but overlooked downside of GLP-1 based therapies which as she explains, “can impair heart rate variability.” This consideration of the autonomic effects of these drugs will be eye-opening to many.  In fact, recent human studies demonstrate that GLPs increase resting heart rate while impairing parasympathetic tone, and heart rate variability. In effect, they are damaging several important hallmarks of healthy aging.

These autonomic effects appear related to the continuous receptor stimulation and may contribute to many of the other downsides: fatigue, impaired recovery, and reduced muscle preservation. This points to an interesting conundrum: These drugs while promoting longevity by reducing weight and glycemic excursions, may also hamper it by challenging autonomic balance and creating downstream problems. This realization makes Koff’s emphasis on proper nutrition, physical activity, and comprehensive lifestyle change even more salient.

Long-Term Weight Maintenance

Patients frequently ask whether GLP-1 medications must be used indefinitely. Koff addresses this question directly and candidly.  She writes that neither clinicians nor manufacturers can reliably predict long-term individual needs. Rather than framing discontinuation as success or failure, she positions it as a test of ecosystem readiness.

A major strength of Your Best Shot is its sustained attention to body composition. Koff repeatedly emphasizes that scale weight alone is an insufficient marker of success, particularly in patients using GLP-1 drugs.

Koff explains that stopping hormone replacement without restoring endogenous function predictably leads to relapse. “If you replace your body’s own hormones,” she notes, “going off it without addressing the preexisting suboptimal function is a recipe for a return to the prior results.”

This perspective is particularly useful for clinicians navigating insurance-driven discontinuation, where patients may be forced off a GLP-1 therapy before physiologic resilience has been established. 

Your Best Shot provides structured guidance for tapering, maintenance dosing, and non-pharmacologic support strategies, helping clinicians reframe the conversation around preparedness rather than permanence.

GLP-1 Supplements & Clinical Integrity

In an environment saturated with marketing claims around “natural Ozempic,” Koff’s evidence-aware approach to supplements is another notable strength of her book. She states unequivocally, “There is no ‘nature’s Ozempic’ and there likely never will be.” She differentiates between GLP-1–activating compounds found in supplements and pharmacologic agonists, explaining the limited but potentially supportive role of the former within a comprehensive plan.

By clearly outlining the benefits, limitations, and appropriate use cases for supplements, such as rectifying well-documented nutrient insufficiencies resulting from GLP drugs, or mitigating GI complaints, Koff maintains clinical credibility while offering practical options for patients. This balanced perspective is particularly valuable for clinicians seeking to integrate nutrition and supplementation without compromising scientific rigor.

Real World Complexity

Your Best Shot succeeds because it reflects the complexity of real-world clinical care. Koff acknowledges constraints such as time, insurance coverage, patient fatigue, and life stressors, while still advocating for thoughtful, personalized interventions. The book’s case-based format mirrors clinical encounters, making it both relatable and instructive.

For clinicians, the book offers language, frameworks, and practical strategies that can immediately improve counseling around GLP-1 therapy. For patients, it provides empowerment without oversimplification, emphasizing that sustainable weight health is built through physiology, not willpower alone.

By clearly outlining the benefits, limitations, and appropriate use cases for supplements, such as rectifying well-documented nutrient insufficiencies resulting from GLP drugs, or mitigating GI complaints, Koff maintains clinical credibility while offering practical options for patients.

As you consider GLP-1 based therapies for patients, make sure to recommend this book alongside the prescription.  In an era of rapid pharmacologic expansion, Your Best Shot offers a much-needed systems-based roadmap for using GLP-1 therapies wisely, ethically, and sustainably—protecting digestion, preserving muscle, and prioritizing long-term health over short-term weight loss. 

Ashley Koff will be providing a keynote presentation and workshop on Nutritional Considerations in the GLP-1 Era at UCI Susan Samueli Integrative Health Institute Nutrition & Supplementation in Clinical Care Conference January 29-February 1, 2026 at the Westin Carlsbad Resort & Spa, Use HPC15 for 15% off in person or virtual attendance.