Why You’re Stuck: GLP-1 Plateaus (And How to Break Through)

Jun 20, 2025

Dive into the world of GLP-1 peptides and the weight loss plateaus they often bring. Discover the hormonal players like leptin and ghrelin that influence our metabolism. Learn why plateaus aren't failures but rather adjustments of the body's weight set point. Get practical strategies to overcome these hurdles, from tweaking your diet to ramping up physical activity. This engaging discussion sheds light on navigating the ups and downs of weight loss while empowering listeners to break through their stalls.

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INSIGHT

Weight Loss Plateaus Are Inevitable

Weight loss plateaus are universal due to the body's drive for homeostasis.
GLP-1 peptides accelerate weight loss but plateaus still occur naturally over time.

INSIGHT

GLP-1 Weight Loss Trajectory

GLP-1 peptides cause rapid initial fat loss followed by gradual slowing and plateauing.
Higher doses and heavier starting weights delay the plateau but do not prevent it.

INSIGHT

Metabolic Adaptation Causes Plateaus

Plateau is a body's adaptive response called metabolic adaptation or adaptive thermogenesis.
This process reduces energy expenditure to defend against continued weight loss.

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In this video, I dive deep into the reasons behind the infamous “GLP plateau”—that frustrating point where fat loss on GLP-1 peptides like semaglutide, tirzepatide, and retatrutide comes to a grinding halt. I break down the physiological, hormonal, and lifestyle factors that drive plateaus, plus practical, science-backed solutions to get results moving again.

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Timestamps

0:00 – Introduction: Why Do GLP-1 Plateaus Happen?
0:35 – Why Weight Loss Plateaus Are Universal
1:22 – How GLP-1s Work (Mechanisms: Semaglutide, Tirzepatide, Retatrutide)
2:36 – Typical Weight Loss Trajectory on GLP-1s
3:18 – When (and Why) Most People Plateau
4:55 – Plateau ≠ Failure: The New Weight Set Point
5:39 – Physiological & Metabolic Causes of Plateaus
6:26 – Resting Metabolic Rate Drop & Adaptive Thermogenesis
7:31 – Decreased Thermogenesis, Exercise Efficiency, & Mitochondria
8:42 – Muscle Loss and Its Impact on Plateaus
9:44 – NEAT (Non-Exercise Activity Thermogenesis) Drops
10:18 – Why the Body Adapts: Our Ancestral Survival Mechanism
11:06 – Hormonal Adaptations: Leptin, Ghrelin, Insulin
13:03 – Leptin Drop: Increased Hunger, Lower Metabolism
13:41 – Ghrelin Rise: Appetite Returns
15:17 – Insulin, Metabolic Health & Fat Loss
17:20 – Thyroid Hormones: T3, Metabolic Rate, and the Plateau
19:03 – Cortisol, Stress, and Fat Storage
20:07 – Sex Hormones: Testosterone, Fat Loss, and Plateaus
21:46 – Amylin, Neuropeptide Y, and Brain Pathways
22:44 – Behavioral & Lifestyle Factors: NEAT, Adherence, Calorie Creep
24:44 – Psychological Fatigue, Sleep, Diet Quality, & Hydration
28:27 – Is It a True Plateau? Body Fat vs. Weight Loss
28:32 – Pharmacological Tolerance & Dosing Issues
30:00 – Appetite Pathways and Receptor Desensitization
31:52 – Dose Ceiling: When More Isn’t Always Better
33:26 – Strategies to Break Through a Plateau
34:16 – Re-evaluating Diet: Macros, Sugar Diet, and Tracking
34:45 – Activity, Resistance Training, and NEAT
35:03 – Sleep, Stress, Thyroid, and Other Medications
35:44 – Add-On Pharmacology: LDN, Cagrilintide, Leptin Analogs
37:01 – Mitochondrial Pathways: BAM15, SLU-PP-332, Carnitine
37:50 – Cycling, Refeeds, and Metabolic Resensitization
39:55 – Fasting, Intermittent Fasting, and Nutrition
40:08 – Recap: Everyone Plateaus—How Will You Respond?
41:02 – Thank You & Outro