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SELECT, STEP, SURPASS, SURMOUNT & FLOW: What the Landmark Semaglutide and Tirzepatide Trials Actually Prove (2026)

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By Dr. Frank Yap, MD  |  Medically reviewed by One Day MD Review Team  |  Last updated: August 2026 Quick Answer SELECT showed that semaglutide 2.4 mg cuts major cardiovascular events by 20% in people with overweight/obesity and existing heart disease who do not have diabetes. The STEP program (STEP 1–5, STEP 8, and the newer STEP UP trials) established semaglutide's weight-loss profile, with losses ranging from roughly 10% to over 20% of body weight depending on dose, population, and duration. The SURPASS program showed that tirzepatide — a dual GIP/GLP-1 agonist — produces larger HbA1c and weight reductions than semaglutide in type 2 diabetes, and the newly published SURPASS-CVOT (December 2025) confirmed tirzepatide is at least as cardioprotective as dulaglutide. FLOW showed semaglutide cuts major kidney disease events by 24% in people with type 2 diabetes and chronic kidney disease, which led the FDA to approve a dedicated kidney-protection indic...
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NAC vs NAD vs NR vs NMN vs Niacin: What Are the Differences?

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By the One Day MD Editorial Team  |  Originally published September 2020  |  Last updated and medically fact-checked: August 2026 NAD, NAD+, NADH, NR, NMN, niacin, niacinamide, and NAC — these overlapping names cause constant confusion, and understandably so. Some are simply different names for the same molecule. Others are metabolic precursors that your body converts, step by step, into NAD+. One of them, NAC, isn't related to NAD+ metabolism at all. This guide breaks down what each compound actually does, how the human evidence stacks up as of 2026, and where the real safety trade-offs lie — including the January 2026 head-to-head human trial that finally pitted NR against NMN directly, and the FDA's 2025 reversal on NMN's legal status. Quick Answer NAD+ is the coenzyme your cells actually need for energy production and DNA repair, and it can't be taken as an oral supplement because it's too large a molecule to survive digestion intact. NR, NMN, n...
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Ivermectin for Parkinson’s and Dementia: Analyzing the Neuroprotective Molecular Evidence and Clinical Case Reports (2026)

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Scientific Review & Regulatory Audit by the Clinical Editorial Team The therapeutic paradigm for progressive neurodegenerative disorders like Parkinson’s disease (PD) and various forms of dementia faces a critical bottleneck. Standard pharmacology, primarily anchored by levodopa (L-DOPA) for Parkinson’s and acetylcholinesterase inhibitors for dementia, remains strictly symptomatic. These options frequently suffer from diminishing efficacy and significant side-effect profiles like L-DOPA-induced dyskinesia over long-term use. Consequently, the pharmaceutical community has focused heavily on drug repurposing—identifying established, safety-vetted compounds capable of crossing pathways to modify disease progression. An unexpected frontline candidate emerging in this space is ivermectin. Traditionally classified as a broad-spectrum antiparasitic agent, a surge of preclinical studies between 2020 and 2024 has unveiled its complex, multi-targeted pharmacodynamics within the mam...
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How Many Years Can a Healthy Lifestyle Add to Your Life? The Evidence on Diet, Exercise, Supplements & Anti-Aging Drugs (2026)

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Short answer: A healthy lifestyle may add years to life—and potentially a decade or more in some populations—but there is no scientifically valid number that applies to everyone. The strongest evidence suggests that the biggest gains come from a combination of not smoking, regular physical activity, a high-quality diet, maintaining a healthy body weight, and controlling major cardiovascular and metabolic risk factors . One influential U.S. analysis estimated that people who followed five low-risk lifestyle factors at age 50 had a projected life expectancy about 14 years longer for women and 12 years longer for men than people following none of those factors. However, this was a prospective observational analysis combined with life-table modelling—not a randomized trial proving that each person will live exactly 12–14 years longer. That distinction matters. It is tempting to interpret longevity studies as if they were a prescription for an extra number of years: exercise gi...
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Testosterone, Men's Health & Healthy Aging: Low T, Testosterone Replacement and the Science of Anti-Aging

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Testosterone is one of the most important hormones in male health. It influences sexual function, muscle mass, bone health, red-blood-cell production, body composition and aspects of mood and energy. Testosterone levels also tend to decline as men age, creating growing interest in testosterone testing, testosterone replacement therapy (TRT), men's health optimization and longevity. Interest in testosterone treatment is also increasing again. New 2026 data from Epic Research show that testosterone prescribing rates in the United States have begun rising again after nearly a decade of decline. The trend is important because it suggests a renewed clinical and consumer focus on testosterone, men's health and hormonal aging—but a rise in prescribing does not itself prove that testosterone therapy is appropriate for every man. The central question remains: Does a man have clinically meaningful testosterone deficiency, what is causing it, and is testosterone replacement lik...
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Top Peptide Protocols 2026: Best Stacks for Fat Loss, Recovery, Anti-Aging & Longevity

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By Dr. Frank Yap, MD  |  Originally published April 2026  |  Fully updated August 26, 2026 for the FDA's July 2026 compounding committee vote Quick Answer As of August 2026, GLP-1 receptor agonists (semaglutide, tirzepatide) remain the only peptides in this guide with full FDA approval. On July 23–24, 2026, an FDA advisory committee (PCAC) recommended adding BPC-157, KPV, TB-500, MOTS-c, Semax, and Epitalon to the list of substances compounding pharmacies may use — but that vote is non-binding, and none of the six is lawful to compound yet; formal rulemaking is expected to take 12–24 months. Separately, AOD-9604 failed its pivotal human obesity trial back in 2007. The best human evidence among the non-GLP-1 peptides here belongs to topical GHK-Cu (skin) and Selank (anxiety); the weakest belongs to BPC-157 and TB-500 (mostly animal data). Any protocol should run through a licensed physician — not a gray-market vendor. Medical & regu...
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Preventive Medicine & Longevity Science (2026)

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An evidence-based guide to reducing chronic disease risk, extending healthspan, and understanding what truly works — beyond hype, supplements, and shortcuts. This page serves as the central hub for OneDayMD’s coverage of preventive medicine, cancer prevention, cardiometabolic health, and longevity science, grounded in epidemiology, clinical trials, and systems biology. What This Hub Covers (Quick Overview) This hub explains: What preventive medicine actually means in modern clinical science The difference between lifespan and healthspan Which interventions reduce disease risk with high-quality evidence Where longevity science is promising — and where it becomes speculation How lifestyle, medications, and emerging tools interact over decades It is designed for readers who want risk reduction, not biohacking fantasy . Executive Summary Preventive medicine focuses on reducing the probability of disease before it occurs , rather than treating pathology after it is established. Longevity ...
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GLP-1 Drugs, Vitamin B1 and Wernicke Encephalopathy: What Happens When Weight Loss Goes Too Far?

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GLP-1 drugs can be highly effective for weight loss, but extreme appetite suppression, persistent nausea or vomiting, and very rapid weight loss can create a nutritional problem that is easy to overlook. One of the most serious possibilities is thiamine (vitamin B1) deficiency leading to Wernicke encephalopathy , a neurological emergency. Recent case reports, a 2025 pharmacovigilance analysis and a 2026 systematic review have raised a safety signal involving semaglutide, tirzepatide and other GLP-1-based therapies . The evidence remains limited and does not establish that GLP-1 drugs directly cause Wernicke encephalopathy in most users. Instead, the leading concern is an indirect pathway involving markedly reduced food intake, gastrointestinal intolerance, nutritional depletion and rapid weight loss . ( Gras et al., 2025 ; Goldman et al., 2026 ; Bidesie & Oudman, 2026 .) Key takeaway: The concern is not that everyone taking a GLP-1 medication ...
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9 Best Berberine Supplements (2026 Review): Evidence, Dosage & New EU Safety Data

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By Dr Frank Yap, MD | Medically reviewed by the One Day MD Editorial Team | Last updated: August 2026 | Original publication: March 2023 Quick Answer A 2024–2025 meta-analysis of 50 RCTs (4,150 patients) confirms berberine modestly but reliably lowers fasting glucose, HbA1c, LDL cholesterol and inflammatory markers in type 2 diabetes and metabolic syndrome — solid, Tier 1a evidence. It is not "nature's Ozempic." Semaglutide produces roughly 10–15%+ body-weight loss in trials; berberine averages only about 2–4 lb a month. The mechanisms and effect sizes aren't comparable. Typical dosing is 500 mg, 2–3x daily with meals (1,000–1,500 mg/day). Bioavailability — not the milligram number on the label — is the biggest real difference between brands. New in 2026: A draft EU/UK scientific opinion (EFSA/COT, March 2026) flagged in-vitro genotoxicity signals, confirmed the CYP3A4 drug-interaction risk, and stated that regulators cannot yet establish a formal "...
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Why Keto Can Dramatically Raise LDL While Triglycerides Fall: The Lean Mass Hyper-Responder Phenomenon

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Why does LDL cholesterol sometimes rise dramatically on a ketogenic diet while triglycerides fall and HDL cholesterol rises? This is one of the most intriguing and controversial lipid responses associated with very-low-carbohydrate diets. For many people, a ketogenic diet produces a relatively modest change in LDL cholesterol. But a subset—particularly some lean individuals—can experience a much larger increase, occasionally reaching LDL-C levels above 300, 400, or even 500 mg/dL. At the same time, triglycerides may fall dramatically and HDL-C may rise. LDL-C ↑↑↑ Triglycerides ↓↓↓ HDL-C ↑ This combination is commonly referred to in the research literature as the Lean Mass Hyper-Responder (LMHR) phenotype. The phenomenon is important because it challenges the assumption that LDL and triglycerides must always move together. It also raises a difficult clinical question: what does dramatically elevated LDL mean when the individual otherwise appears metabolically healthy?...
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