Top Weight Loss Peptides: Semaglutide, Tirzepatide & More

 

One notable benefit of peptides is their potential to aid in weight loss.  There are several new peptides that scientists are researching. We will explore top choices and best peptides that can help find the best peptide or compound for your research project.

How Do Peptides Work for Weight Loss

Some peptides promote weight loss by stimulating lipolysis, the breakdown of body fat. Others inhibit lipogenesis, the process of synthesizing body fat. Additionally, certain peptides help regulate hormones like insulin and glucagon. By boosting insulin release, these peptides help maintain low blood glucose levels, reducing the likelihood of weight gain.

The Role of GLP-1 Peptides

GLP-1 medications were first developed to manage blood sugar levels in people with type 2 diabetes. However, they have recently been recognized for their weight loss benefits. Peptides like Semaglutide and Tirzepatide leverage GLP-1 mechanisms by mimicking its natural effects in the body, which enhances feelings of fullness and reduces calorie intake.

These peptides also contribute to better glycemic control, extending their benefits beyond just weight loss. GLP-1-based therapies positively influence overall metabolic health and lower cardiovascular risks. This marks a new era in sustainable weight management that addresses broader health concerns.

Semaglutide

Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that mimics the GLP-1 hormone, which is released in the gut after eating. It's used primarily for managing chronic weight-related conditions such as Type 2 Diabetes, hypercholesterolemia, and hypertension.

As a GLP-1 receptor agonist, Semaglutide helps regulate blood sugar levels by enhancing insulin secretion and reducing glucagon levels, which prevents the conversion of glycogen to glucose. In addition to its effects on blood sugar, GLP-1 also influences brain areas that control appetite and satiety. Semaglutide can help people who are obese or overweight lose a considerable amount of weight and lower their risk of heart disease, diabetes, and cancer when used in combination with diet and exercise. [1]

Clinical trials have shown that Semaglutide can lead to a 15% reduction in body weight. It achieves this by decreasing appetite and lowering fasting triglycerides and VLDL cholesterol over time. Its long half-life supports effective weight management, which contributed to its FDA approval. [2]

For weight loss, Semaglutide is approved under the brand name Wegovy, with a typical dose of 2.4 mg administered weekly via subcutaneous injections. As demand for weight loss treatments grows, some healthcare providers prescribe other Semaglutide brands, like Ozempic and Rybelsus, off-label for this purpose.

Tirzepatide

Tirzepatide is a relatively new medication approved by the FDA in May 2022. Administered through a weekly injection, Tirzepatide is designed to help lower blood glucose levels when combined with a diabetes-friendly diet and regular exercise, contributing to treating Type 2 diabetes and aiding in weight management.

This medication is distinct because it combines the effects of two types of incretin hormones: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Both hormones are naturally released after eating and play a role in regulating blood sugar. Tirzepatide mimics their actions by prompting the pancreas to produce more insulin and signalling the liver to reduce glucose production, which helps lower blood glucose levels. [3]

For weight loss, Tirzepatide helps by reducing the appetite and extending feelings of fullness. It accomplishes this by signaling to the brain that you are full, which helps decrease calorie intake, and by slowing down the rate at which food moves through the stomach, thereby prolonging satiety. Its dual action on GLP-1 and GIP may lead to more significant weight loss compared to other medications that target only GLP-1.  [3]

Clinical trials have demonstrated that Tirzepatide not only facilitates significant weight loss but also exerts profound effects on glycemic control. Participants in these studies experienced remarkable reductions in body weight, with some losing up to 22.5% of their baseline weight, depending on the dosage administered.

In a trial focusing on obese patients without diabetes, Tirzepatide was administered over 72 weeks. Participants achieved a mean weight loss of up to 20% at the highest dose, showcasing its efficacy as a weight loss agent. This study highlighted Tirzepatide’s potential for treating obesity beyond its effects on diabetes management. [4]

Retatrutide

Retatrutide is an emerging peptide developed by Lilly for treating obesity, diabetes, and fatty liver disease. It is common for diabetes medications to be used for weight management, and Retatrutide is a notable example of this trend. Unlike Semaglutide, which works solely as a GLP-1 agonist, Retatrutide employs a combination of three mechanisms: it is a gastric inhibitory polypeptide (GIP) receptor agonist, a GLP-1 receptor agonist, and a glucagon receptor agonist.  This "triple action" approach may enhance its effectiveness compared to other peptides that are strictly binding on a single receptor. [5]

Retatrutide supports weight loss through several mechanisms. It helps extend feelings of fullness by slowing the rate at which the stomach empties after meals. Additionally, it stabilizes blood sugar levels post-eating by boosting insulin release and promoting the conversion of excess sugar into glucose. By affecting glucagon hormone levels, Retatrutide also aids in appetite suppression and enhances energy expenditure. [5][6]

In recent trials, participants with obesity who received the highest dose of Retatrutide lost an average of 17.5% of their initial weight after about six months. By the end of the 48-week period, the average weight loss was more than 24%, equating to roughly 58 pounds. Additionally, participants on lower doses experienced a weight reduction of 5% to 15%, which is noteworthy given that a 5% to 10% weight loss is often recommended to enhance health outcomes related to blood pressure, cholesterol, pre-diabetes, and metabolic syndrome. [6]

Ipamorelin

Ipamorelin is a synthetic growth hormone secretagogue receptor agonist, closely resembling the natural peptide hormone ghrelin. As a ghrelin analog, ipamorelin effectively stimulates the secretion of growth hormone (GH) and is one of the most selective ghrelin mimetics, meaning it has minimal unintended side effects. Research has explored its potential in stimulating bone formation, treating post-operative ileus, and its effects on weight loss by influencing GH secretion, insulin release, and food intake. [7]

When it comes to weight loss, ipamorelin's role might seem counterintuitive since ghrelin, its natural counterpart, is often called the "hunger hormone." However, ipamorelin's impact on weight management lies in its ability to modify energy balance, promoting lean body mass (muscle gains) over fat mass. When combined with a proper diet and exercise regimen, ipamorelin can significantly enhance fat burning. Rather than simply aiding in weight loss, ipamorelin is more accurately described as promoting the development of lean body mass.

Learn more about this peptide in our Ipamorelin Guide.

Tesofensine

Tesofensine is a serotonin–noradrenaline–dopamine reuptake inhibitor, often referred to as a triple reuptake inhibitor. This means it blocks the reabsorption of three key neurotransmitters: serotonin, norepinephrine, and dopamine. By preventing their reuptake, Tesofensine increases the levels of these neurotransmitters in the brain. The therapeutic benefits of Tesofensine are largely due to this mechanism, as each neurotransmitter plays a crucial role in different brain areas. [8]

Originally developed as a treatment for Alzheimer's and Parkinson's diseases, Tesofensines’ trials were halted due to its limited effectiveness in addressing these conditions. However, a significant side effect observed during these trials was substantial weight loss, particularly in overweight or obese patients. Tesofensine primarily aids weight loss by inducing a feeling of satiety, thereby reducing appetite. It tricks the brain into believing the gastrointestinal tract is full by binding to the dopamine D1 receptor and alpha-1 adrenoceptors, which are typically activated by norepinephrine and epinephrine.

Clinical studies have shown that Tesofensine can reduce body weight by approximately 4.5% to 10.6% over a 24-week period when combined with diet, exercise, and lifestyle modifications. In addition to its weight-loss properties, Tesofensine offers several other health benefits. It can improve insulin sensitivity, which may benefit individuals with Type II diabetes. [9]

A Phase 3 trial assessed Tesofensine's efficacy in obese patients. Over 24 weeks, Tesofensine led to a mean weight loss of 10% compared to placebo. The study confirmed Tesofensine's potential as a weight loss agent, driven by its action on neurotransmitter reuptake inhibition. [10]

Learn more about Tesofensine.

Side Effects of Peptides for Weight Loss

Although each peptide may have its own specific side effects, some common ones typically involve the gastrointestinal tract, including nausea, cramping, constipation, and diarrhea. These side effects are generally mild and tend to resolve over time as your body adjusts to the medication.

Additional side effects can include low blood sugar, reactions at the injection site (such as redness, swelling, or pain), headache, dizziness, and fatigue. However, in rare instances, more serious side effects may occur, such as gastroparesis (a condition that slows or stops the movement of food from the stomach to the small intestine), pancreatitis, and changes in vision.

The Future of Peptides for Weight Loss

The future of peptides for weight loss is promising and transformative. As research continues to advance, peptides like Semaglutide, Tirzepatide, and Retatrutide are setting new standards in weight management. These therapies not only offer substantial weight reduction but also improve overall metabolic health, addressing broader issues like diabetes and cardiovascular risk.

It is anticipated these peptides will redefine weight management by delivering more targeted, efficient, and sustainable outcomes. As these innovations evolve, peptides are likely to become a cornerstone in obesity management, offering hope to those who have struggled with traditional methods. However, as with any emerging treatment, it's necessary to continue monitoring the long-term effect. With more clinical trials on the way, we will hopefully see peptides as a ground-breaking weight loss option.

References

[1] Mahapatra MK, Karuppasamy M, Sahoo BM. Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes. Rev Endocr Metab Disord. 2022 Jun;23(3):521-539. doi: 10.1007/s11154-021-09699-1. Epub 2022 Jan 7. PMID: 34993760; PMCID: PMC8736331.

[2] Lincoff, A. M., Brown-Frandsen, K., Colhoun, H. M., Deanfield, J., Emerson, S. S., Esbjerg, S., Hardt-Lindberg, S., Hovingh, G. K., Kahn, S. E., Kushner, R. F., Lingvay, I., Oral, T. K., Michelsen, M. M., Plutzky, J., Tornøe, C. W., & Ryan, D. H. (2023). Semaglutide and cardiovascular outcomes in obesity without diabetes. New England Journal of Medicine, 389(19), 2221-2232. https://doi.org/

[3] Dubey, A.. "tirzepatide." Encyclopedia Britannica, August 8, 2024. Britannica Ttirzepatide.

[4] Ryan, D.H., Lingvay, I., Deanfield, J. et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nat Med 30, 2049–2057 (2024). https://doi.org/10.1038/s41591-024-02996-7

[5] Kaur, Manmeet & Misra, Saurav. (2024). A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity. European Journal of Clinical Pharmacology. 80. 1-8. 10.1007/s00228-024-03646-0.

[6] Naeem M, Imran L, Banatwala UESS. Unleashing the power of retatrutide: A possible triumph over obesity and overweight: A correspondence. Health Sci Rep. 2024 Feb 5;7(2):e1864. doi: 10.1002/hsr2.1864. PMID: 38323122; PMCID: PMC10844714.

[7] Sinha DK, Balasubramanian A, Tatem AJ, Rivera-Mirabal J, Yu J, Kovac J, Pastuszak AW, Lipshultz LI. Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Transl Androl Urol. 2020 Mar;9(Suppl 2):S149-S159. doi: 10.21037/tau.2019.11.30. PMID: 32257855; PMCID: PMC7108996.

[8] Appel L, Bergström M, Buus Lassen J, Långström B. Tesofensine, a novel triple monoamine re-uptake inhibitor with anti-obesity effects: dopamine transporter occupancy as measured by PET. Eur Neuropsychopharmacol. 2014 Feb;24(2):251-61. doi: 10.1016/j.euroneuro.2013.10.007. Epub 2013 Oct 22. PMID: 24239329.

[9] Astrup A, Madsbad S, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Nov 29;372(9653):1906-1913. doi: 10.1016/S0140-6736(08)61525-1. Epub 2008 Oct 22. PMID: 18950853.

[10] Rebello CJ, Greenway FL. Obesity medications in development. Expert Opin Investig Drugs. 2020 Jan;29(1):63-71. doi: 10.1080/13543784.2020.1705277. Epub 2019 Dec 19. PMID: 31847611; PMCID: PMC6990416.