In our foundational guide on geromedicine, we established that biological aging is the single greatest risk factor for almost every chronic illness. By understanding and targeting the underlying cellular drivers of aging, proactive medicine aims to prevent multiple chronic diseases simultaneously [1].
For patients, the most important question is practical: What can we actually do about it today?
While wellness culture often swings between two extremes—either dismissing all anti-aging science as hype or pushing unproven grey-market supplements—evidence-based clinical practice occupies a rational middle ground.
While no medication is FDA-approved specifically to "reverse aging," a select group of pharmaceutical agents and metabolic protocols—termed candidate gerotherapeutics—show varying degrees of evidence for extending healthspan [1, 2].
Crucially, these candidates exist along a wide spectrum of human clinical evidence, ranging from large randomized outcome trials to early-stage feasibility studies [1, 2]. Here is how our telemedicine practice at delaeMD stratifies candidate gerotherapeutics, the evidence and caveats for each, and how we approach safe, transparent clinical decision-making.
1. The delaeMD Framework: High Benefit, Low Risk, Total Transparency
At delaeMD, candidate gerotherapeutics are never prescribed as magic pills, nor are they used as a substitute for foundational exercise, nutrition, and sleep [1].
Instead, we view gerotherapeutics as targeted clinical tools that can be layered onto a strong lifestyle foundation for appropriately screened patients [1]. This commitment to scientific rigor is built directly into our practice's DNA: Dr. Michael Leone, one of our physicians at delaeMD, co-authored a landmark prioritization framework for candidate gerotherapeutics alongside renowned geroscience researcher Dr. Nir Barzilai [2]. Published in Medical Research Archives, their work systematically evaluates and ranks repurposed FDA-approved drugs based on the quality of preclinical and human clinical evidence [2].
Our clinical evaluation framework rests on three non-negotiable principles:
Clear Evidence Stratification: We explicitly distinguish between therapies supported by large human outcome trials (hard clinical endpoints) versus investigational agents supported primarily by preclinical models or small pilot studies [1, 2].
Favorable Risk-to-Benefit Stratification: We only consider candidates that demonstrate a high potential for clinical benefit coupled with a well-characterized safety profile in appropriately selected individuals [1, 2].
Shared Medical Decision-Making: Before initiating any therapy, we conduct an unfiltered discussion with the patient, reviewing the quality of human evidence, potential side effects, exercise interactions, required laboratory monitoring, and long-term goals.
2. Established Cardiometabolic Interventions with Robust Outcome Data
The strongest, most replicated human clinical trial evidence in geroscience currently comes from agents approved for cardiometabolic disease that deliver profound systemic and anti-inflammatory protections [1, 2].
GLP-1 Receptor Agonists
The Evidence: Originally developed for type 2 diabetes and obesity, GLP-1 receptor agonists (such as semaglutide and tirzepatide) modulate glucose-dependent insulin secretion, reduce visceral adiposity, and downregulate systemic vascular inflammation [1, 3]. Landmark clinical trials (such as the SELECT trial) demonstrate major reductions in cardiovascular mortality, major adverse cardiovascular events (MACE), and chronic kidney disease progression in non-diabetic adults with elevated cardiovascular risk [3].
Clinical Context: While frequently discussed in longevity circles, these benefits stem primarily from treating underlying pathology—visceral adiposity, insulin resistance, and vascular inflammation [1, 3]. For patients with elevated cardiometabolic risk or visceral fat, GLP-1 therapies offer some of the strongest human outcome data in modern preventive care [3].
SGLT2 Inhibitors
The Evidence: Sodium-glucose cotransporter-2 (SGLT2) inhibitors (such as empagliflozin and dapagliflozin) promote glucosuria, shift cellular energetics toward ketone utilization, and reduce intraglomerular pressure [1, 2]. Large randomized controlled trials demonstrate robust reductions in heart failure hospitalizations, kidney disease progression, and cardiovascular mortality across both diabetic and non-diabetic populations [1, 2].
Clinical Context: The American College of Cardiology identifies SGLT2 inhibitors as having among the strongest human clinical trial evidence among candidate gerotherapeutics [1]. They provide profound cardio-renal protection, making them a cornerstone discussion for patients with subclinical cardiovascular or renal risk [1, 2].
3. Investigational & Translational Candidates
Beyond established cardiometabolic drugs, several agents show compelling preclinical promise but possess more limited or nuanced human clinical trial data [1, 2, 4].
Rapamycin
The Evidence: Rapamycin inhibits mechanistic target of rapamycin complex 1 (mTORC1), a master nutrient sensor regulating cellular growth and autophagy [1]. It is the most consistent pharmaceutical candidate for extending lifespan across animal species in the National Institute on Aging’s Interventions Testing Program [1]. Early human trials (such as everolimus studies and the RAPA-EX-01 trial) demonstrate that low-dose periodic (weekly) administration is feasible, well-tolerated, and can enhance immune response in older adults [1, 4].
Clinical Context: Human data for healthspan extension remain entirely experimental [1, 4]. While short-term feasibility studies exist, rapamycin completely lacks long-term human outcome trials demonstrating disease prevention or extended healthspan [1, 4]. Given the absence of confirmed clinical outcomes, rapamycin is ideally suited for formal clinical trial enrollment rather than routine off-label prescribing. Any off-label consideration requires explicit counseling regarding its experimental status, potential metabolic side effects (such as altered lipid profiles or glucose tolerance), and strict laboratory monitoring [1, 4].
Metformin
The Evidence: Metformin activates AMPK and suppresses hepatic gluconeogenesis, improving insulin sensitivity [1, 2]. Observational studies in diabetic patients showed reduced rates of cardiovascular disease, cancer, and cognitive decline [1, 5]. The ongoing TAME (Targeting Aging with Metformin) trial is evaluating its ability to delay multi-morbidity in non-diabetic humans [1, 5].
Critical Exercise Nuance: Clinical trials in non-diabetic older adults demonstrate that metformin can attenuate exercise-induced gains in muscle mass, strength, and mitochondrial adaptations [5]. Because preserving skeletal muscle mass is a primary goal of healthspan care, metformin is evaluated cautiously in non-diabetic individuals who are actively engaged in structured resistance training [1, 5].
Fasting-Mimicking Diet
The Evidence: The Fasting-Mimicking Diet (FMD) is a structured, plant-based, 5-day periodic fasting protocol designed to downregulate mTOR and IGF-1 signaling while providing enough energy to maintain compliance [6]. Secondary exploratory analyses of small randomized trials demonstrate that 3 monthly FMD cycles reduce body weight, trunk fat, systolic blood pressure, hepatic fat, and algorithmic estimates of biological age [6].
Clinical Context: FMD trials represent small, hypothesis-generating pilot studies rather than large outcome trials [6]. Crucially, while studies report reductions in algorithmic "biological age" markers, these composite biomarkers remain unvalidated as surrogate endpoints for hard clinical outcomes [7]. Furthermore, FMD research centers on a proprietary commercial product (ProLon), a commercial context that patients should understand when evaluating the literature [6].
4. What to Expect in a Healthspan Consultation
If you are interested in exploring candidate gerotherapeutics, care begins with diagnostic clarity, not a prescription pad.
A comprehensive healthspan evaluation includes:
Baseline Biomarker Mapping: Advanced lipid panels (ApoB, Lp(a)), glycemic markers (fasting insulin, HbA1c), inflammatory indicators (hs-CRP), and organ function markers [1].
Body Composition & Cardiovascular Screening: Assessing visceral adipose tissue, lean skeletal muscle mass, and vascular risk [1, 3].
Personalized Risk-Benefit Review: Reviewing the clinical literature together, mapping candidate therapies against your health profile, and ensuring medications do not interfere with physical training adaptations [1, 5].
Continuous Clinical Tracking: Regular follow-up laboratory testing and clinical check-ins to monitor safety, adjust dosages, and confirm therapeutic efficacy over time [1].
Aligning Science with Patient Care
Geromedicine is not about chasing online trends or buying into unverified supplement stacks. It is about applying rigorous clinical science to help you make informed decisions about your long-term health trajectory [1, 2].
Whether your strategy relies entirely on optimizing physical fitness and nutrition or includes carefully monitored candidate therapeutics like GLP-1s, SGLT2 inhibitors, rapamycin, metformin, or the Fasting-Mimicking Diet, the objective remains the same: protecting your physical independence, cognitive clarity, and vitality for decades to come.
Explore where candidate aging interventions stand on the clinical evidence spectrum using our free Gerotherapeutics Dashboard, or evaluate your broader physical and metabolic metrics with our Healthspan Engine.
(Disclosure: The Gerotherapeutics Dashboard and Healthspan Engine are free educational tools provided by delaeMD.)
References
Forman DE, Kuchel GA, Newman JC, et al. Impact of Geroscience on Therapeutic Strategies for Older Adults With Cardiovascular Disease: JACC Scientific Statement. Journal of the American College of Cardiology. 2023;82(7):631-647.
Leone M, Barzilai N. An Updated Prioritization of Geroscience-Guided FDA-Approved Drugs Repurposed to Target Aging. Medical Research Archives. 2024;12(2):5138.
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). The New England Journal of Medicine. 2023;389(24):2221-2232.
Stanfield B, Leroux B, Kaeberlein M, Jones J, Lucas R. Exercise and Weekly Sirolimus (Rapamycin) in Older Adults: RAPA-EX-01 Randomised, Double-Blind, Placebo-Controlled Trial. Journal of Cachexia, Sarcopenia and Muscle. 2026;17(2):e70274.
Kritchevsky SB, Cummings SR. Geroscience. JAMA. 2025;334(12):1094-1102.
Brandhorst S, Levine ME, Wei M, et al. Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Nature Communications. 2024;15(1):1309.
Moqri M, Herzog C, Poganik JR, et al. Validation of Biomarkers of Aging. Nature Medicine. 2024;30(2):360-372.
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