Peptides for Weight Loss: A Comprehensive Guide to Current and Emerging Therapies
Peptide-based therapies are transforming weight management by targeting hormonal pathways that regulate appetite, metabolism, and body fat distribution. This article explores both FDA-approved and investigational peptides with potential or proven benefits for weight loss and metabolic health.
GLP-1 Receptor Agonists: Semaglutide, Tirzepatide, Retatrutide, and Survodutide
Glucagon-like peptide-1 (GLP-1) receptor agonists enhance insulin secretion, suppress appetite, and delay gastric emptying, leading to reduced calorie intake and weight loss.
-
Semaglutide: Approved as Ozempic (type 2 diabetes) and Wegovy (obesity), semaglutide has achieved up to 15% body weight reduction in clinical trials.
-
Tirzepatide: Marketed as Mounjaro (diabetes) and Zepbound (obesity), tirzepatide combines GLP-1 and GIP receptor agonism, achieving up to 22% weight loss, the highest among approved drugs.
-
Retatrutide: Currently in Phase 3 trials, this triple agonist (GLP-1, GIP, and glucagon receptors) has shown 24.2% average weight loss in a Phase 2 study.
-
Survodutide: An investigational dual GLP-1/glucagon receptor agonist, early trials have shown meaningful weight loss and metabolic improvements.
Amylin Analog: Cagrilintide
Cagrilintide is a long-acting amylin analog that enhances satiety and reduces food intake. When combined with semaglutide, it has delivered superior weight loss compared to either agent alone.
Cagrilintide can be used in combination with any of the GLP-1 medications listed above. Adding Cagrilintide can increase the effectiveness and may decrease the needed dose of GLP-1 medications.
Growth Hormone Secretagogues: Tesamorelin, Ipamorelin, and CJC-1295
These peptides stimulate growth hormone (GH) release, potentially promoting fat reduction and lean mass preservation.
-
Tesamorelin: FDA-approved for HIV-associated lipodystrophy; shown to reduce visceral adiposity and improve liver fat.
-
Ipamorelin: A GH secretagogue that increases GH without significant impact on cortisol or prolactin. Animal studies support its potential for fat reduction.
-
CJC-1295: A long-acting GHRH analog that boosts IGF-1 and GH, leading to improved body composition.
Mitochondrial Peptide: MOTS-c
MOTS-c is a mitochondrial-derived peptide that has emerged as a promising metabolic regulator.
-
It enhances insulin sensitivity, supports glucose utilization, and promotes fatty acid oxidation.
-
Animal studies and early human data suggest MOTS-c can improve endurance and promote fat loss by activating AMPK (a key metabolic switch).
-
MOTS-c also shows potential for combating age-related metabolic decline and obesity resistance.
Though still investigational, MOTS-c represents an exciting new avenue in peptide-assisted weight management.
Other Investigational Peptides: AOD-9604 and Tesofensine
-
AOD-9604: A fragment of human growth hormone designed to stimulate lipolysis without impacting blood sugar. Preclinical studies have shown body fat reduction.
-
Tesofensine: Originally developed for neurodegenerative disorders, this triple monoamine reuptake inhibitor demonstrated substantial appetite suppression and weight loss in clinical trials.
Conclusion
Peptide therapies offer diverse and promising approaches to weight loss by modulating appetite, metabolism, fat storage, and energy expenditure. While semaglutide and tirzepatide are already widely used, emerging candidates like retatrutide, survodutide, cagrilintide, MOTS-c, and others are expanding the frontier of peptide-assisted weight management.
Always consult with a qualified healthcare provider before initiating any peptide-based therapy.
Here is our Weight Loss Mastery program as well.Â