Peptides and weight loss

GLP-1 medicines

GLP-1 is a hormone released by the intestine that lowers blood sugar after meals and acts on brain areas that control appetite.¹⁵ Drugs that mimic it also slow the movement of food through the gut, which can help a person feel full longer.¹⁶ The GLP-1 and weight loss page and the GLP-1 overview cover the class.

Semaglutide (Wegovy, Ozempic and Rybelsus)

Wegovy (semaglutide injection and tablets) is FDA approved to reduce excess body weight and keep it off long term, alongside a reduced-calorie diet and more physical activity.¹⁷ In the STEP 1 trial of 1,961 adults, average weight change at 68 weeks was -14.9% on semaglutide 2.4 mg, against -2.4% on placebo.¹ Ozempic and Rybelsus contain the same ingredient but are approved for type 2 diabetes, not weight loss.⁵¹⁸ For each product, the prescriber sets the dose. Read What is Semaglutide?, Semaglutide and weight loss, Wegovy and weight loss, Ozempic and weight loss and Rybelsus and weight loss.

Tirzepatide (Zepbound and Mounjaro)

Tirzepatide acts on two hormone receptors, GIP and GLP-1.¹⁹ As Zepbound, it is FDA approved to reduce excess body weight and maintain the loss in adults with obesity, or with overweight plus at least one weight-related condition.⁷ In SURMOUNT-1, a 72-week trial of 2,539 adults without diabetes, average weight change was -15.0% to -20.9% across the three doses, against -3.1% on placebo.²⁸ In SURMOUNT-5, a head-to-head trial in 751 adults, weight change at 72 weeks was -20.2% on tirzepatide and -13.7% on semaglutide.²⁰ Mounjaro, the diabetes brand, is not approved for weight loss.⁶ Read What is Tirzepatide?, Tirzepatide and weight loss and Mounjaro and weight loss.

Retatrutide

Retatrutide is an investigational weekly injection that activates three receptors: GIP, GLP-1 and glucagon.²¹ No regulator has approved it.²² TRIUMPH-1 was a phase 3, 80-week trial in 2,339 adults with obesity and no diabetes.³ Average weight change was -17.6%, -23.7% and -25.0% on the 4, 9 and 12 mg doses, against -3.9% on placebo.³ FDA states it has not been found safe and effective for any condition.²³ Read What is Retatrutide?.

Growth hormone axis peptides

Tesamorelin

Tesamorelin's label says it is not indicated for weight loss because its effect on weight is neutral.²⁴ What it reduced in trials is deep abdominal (visceral) fat.²⁵²⁶ In adults with HIV, that fat fell 15.4% against placebo at 26 weeks.²⁵ In 60 adults with abdominal obesity and reduced growth hormone secretion, it fell 35 square centimeters against placebo over 12 months.²⁶ When treatment stopped, the visceral fat came back.²⁷ Read What is Tesamorelin?, or see Tesamorelin for sale.

Sermorelin

Sermorelin has not been shown to cause weight or fat loss: in 11 healthy older men, six weeks of nightly injections did not change weight, BMI, waist-to-hip ratio or DEXA fat.²⁸ Obesity also blunts the response: peak growth hormone after GRF(1-29) was 8.9 mU/L in 14 obese women, against 28 mU/L in 9 normal-weight women.²⁹ Read Sermorelin and weight loss and What is Sermorelin?, or see Sermorelin for sale.

HGH

Prescription growth hormone (somatropin) is used for growth failure, short bowel syndrome and weight gain in some people with HIV, not for weight loss.³⁰ In a review of trials in healthy older adults, it cut fat mass by 2.1 kg but added 2.1 kg of lean mass, so body weight did not change.³¹³² In adults with diagnosed growth hormone deficiency, the GENOTROPIN label reports lower body fat and waist circumference.³³ Read What is HGH?, or see HGH for sale.

AOD-9604 and HGH Fragment 176-191

Fragments from the end of the growth hormone molecule reduced weight gain and body fat in obese mice.³⁴³⁵ Human trials tested AOD-9604 by mouth or by vein, and in the largest, which enrolled 536 adults with obesity, weight loss did not differ significantly from placebo at 12 weeks.³⁶ FDA concluded in 2024 that there is a lack of evidence of effectiveness for obesity by any route.⁴ Read What is AOD-9604? and What is HGH Fragment 176-191?, or see AOD-9604 for sale and HGH Fragment 176-191 for sale.

CJC-1295, ipamorelin, GHRP-2 and GHRP-6

For GHRP-2, GHRP-6 and ipamorelin, the data point to more eating, not less.³⁸³⁷⁴⁰ GHRP-2 infusions made 7 lean men eat 35.9% more, and raised intake by up to 33.5% in 19 lean and obese adults.³⁸³⁹ A 2026 review calls appetite stimulation a characteristic effect of GHRP-6,³⁷ and in mice ipamorelin increased body fat, leptin and food intake.⁴⁰ The one registered CJC-1295 patient trial, in HIV-related abdominal obesity, was terminated in 2006 and has no posted results.⁴¹ Read What is CJC-1295 with DAC?, What is CJC-1295 No DAC?, What is CJC-1295 + Ipamorelin?, What is Ipamorelin?, What is GHRP-2? and What is GHRP-6?.

Other compounds searched with weight loss

HCG

HCG labels state that it has not been shown to be effective additional therapy for obesity, and that it has no known effect on fat mobilization, appetite or body fat distribution.⁴²⁴³ Double-blind trials in 51 women (1976) and 40 women on the same diet (1990) found no benefit over placebo.⁴⁴⁴⁵ A 1995 analysis of 24 trials found no scientific evidence that HCG treats obesity.⁴⁶ FDA says any loss on the HCG diet comes from severe calorie restriction, not from the hormone.⁴⁷ Read What is HCG?, or see HCG for sale.

MOTS-c

In mice on a high-fat diet, MOTS-c prevented obesity, and treated mice weighed about 20% less after 8 weeks.⁴⁸⁴⁹ It had no effect on weight in mice on a normal diet.⁴⁹ FDA found no clinical studies or human exposure data for MOTS-c.⁵⁰ Read What is MOTS-c?, or see MOTS-c for sale.

No human weight-loss evidence

• KPV. It reduced fat-cell formation in a dish and weight gain in mice on a high-fat diet, with no human studies.¹³¹² Read What is KPV?.
• Melanotan 2. Rodents ate less after it, but in people decreased appetite appeared only as a temporary side effect in a 10-man trial.⁵¹⁵² Read What is Melanotan 2?.
• NAD+. Oral precursors did not change weight or body fat in 25 women with prediabetes over 10 weeks, or body composition in 40 obese men over 12 weeks.⁵³⁵⁴ Read What is NAD+?.
• IGF-1 LR3. Human studies used natural IGF-1, not LR3.⁵⁵⁵⁶ Given with its binding protein for 28 days, it did not change fat mass in recreational athletes.⁵⁵ High doses in 7 obese adults with type 2 diabetes caused mild weight gain and swelling.⁵⁶ Read What is IGF-1?.
• Kisspeptin-10. A kisspeptin infusion in 15 healthy men did not change gut hormones, appetite or food intake.⁵⁷ Read What is Kisspeptin-10?.
• Selank. In a 4-week rat study, it did not change body mass.⁵⁸ Read What is Selank?.
• ARA-290. It has not been tested for weight loss, and its type 2 diabetes trial reported blood sugar and nerve symptom results, not weight change.⁵⁹ Read What is ARA-290?.

How to read this research

Start by separating approved medicines from research compounds. The Wegovy and Zepbound results come from trials of the approved products at label doses, with diet and activity counseling.¹⁹ FDA does not review compounded versions of these drugs for safety, effectiveness or quality, and it calls versions labeled "for research purposes" but sold for human use of unknown quality.²³ Next, look past the end of a trial: much of the lost weight came back when semaglutide or tirzepatide was stopped.¹⁰¹¹ Then check what was lost: both labels say the drugs lower body weight with greater fat loss than lean mass loss, so some lean mass is lost too.⁶⁰⁶¹ Finally, treat animal fat loss with care, since AOD-9604 cut weight gain in obese mice and then failed in people.³⁶ Class side effects are on the GLP-1 side effects page, the Ozempic vs Wegovy page compares the two semaglutide injections, and the blood sugar page covers the diabetes uses.