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Best Peptides for Fat Loss: Evidence-Based Guide

The search for effective fat loss compounds has changed more in the past five years than in the previous fifty. GLP-1 receptor agonists like semaglutide and tirzepatide have produced weight loss results that were once considered impossible without surgery.

The search for effective fat loss compounds has changed more in the past five years than in the previous fifty. GLP-1 receptor agonists like semaglutide and tirzepatide have produced weight loss results that were once considered impossible without surgery. At the same time, older categories -- growth hormone secretagogues, HGH fragments, and GHRH analogs -- continue circulating in clinics and forums, often with claims that outpace their evidence.

This guide ranks every major peptide studied for fat loss based on what clinical trials actually show. Some have data from trials involving thousands of patients over multiple years. Others have never been tested in a properly controlled human study. Knowing where each peptide sits on that spectrum is the first step toward making an informed decision.

Table of Contents

How Peptides Promote Fat Loss

Peptides used for fat loss work through three broad mechanisms. Understanding these helps explain why some compounds produce dramatic results while others barely move the needle.

Appetite suppression and satiety signaling. GLP-1 receptor agonists mimic the incretin hormone GLP-1, which your gut releases after eating. They slow gastric emptying (food stays in your stomach longer), reduce appetite signals in the hypothalamus, and alter reward-based eating behavior. People eat less without white-knuckling a diet. This mechanism drives the 15-25% body weight reductions seen with modern GLP-1 drugs [1, 2].

Direct lipolysis and fat oxidation. Some peptides act on fat cells directly. Growth hormone and its derivatives stimulate the breakdown of stored triglycerides into free fatty acids (lipolysis) and increase fat oxidation. Peptides like AOD-9604 and Fragment 176-191 were designed to isolate this fat-burning activity from growth hormone's other effects [3].

Metabolic rate and body composition changes. Growth hormone-releasing peptides raise GH and IGF-1 levels, which can shift body composition toward more lean mass and less fat mass over time. Compounds like tesamorelin and CJC-1295 work through this pathway, and the effects tend to be more modest than appetite suppression [4].

The GLP-1 class wins on magnitude because appetite is the primary driver of energy balance. A peptide that consistently reduces caloric intake by 20-30% will outperform one that modestly increases fat oxidation -- which is exactly what trial data shows.

FDA-Approved Peptides for Weight Loss

These three compounds have passed the highest bar of evidence: large, randomized, placebo-controlled trials reviewed by the FDA.

Semaglutide (Wegovy)

Semaglutide is the GLP-1 receptor agonist that started the modern obesity treatment revolution. Administered as a once-weekly injection, it remains one of the most studied weight loss medications in history.

Clinical trial results:

  • STEP 1 trial: 1,961 adults without diabetes lost an average of 14.9% of body weight over 68 weeks, compared to 2.4% with placebo. Over half (51%) of participants on semaglutide lost more than 15% of their body weight [1].
  • STEP 5 trial: Two-year data confirmed weight loss was sustained at 104 weeks, addressing early concerns about durability [5].
  • STEP 8 trial (head-to-head): Semaglutide produced 15.8% weight loss versus 6.4% with liraglutide over 68 weeks [6].
  • STEP UP trial (higher dose): A newer 7.2 mg dose achieved 20.7% weight loss at 72 weeks, with one-third of participants losing 25% or more of their body weight [7].
  • SELECT trial (4-year data): In patients with cardiovascular disease, semaglutide maintained a 10.2% weight reduction through 4 years while cutting major cardiovascular events by 20% [8].

Semaglutide activates GLP-1 receptors in the gut and brain, slowing gastric emptying and reducing hunger. Its long half-life allows once-weekly dosing. It is approved for adults with a BMI of 30+, or 27+ with at least one weight-related condition, and for adolescents aged 12+.

Tirzepatide (Zepbound)

Tirzepatide targets two receptors -- GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) -- which is why it is called a "dual agonist." This two-pronged approach produces the highest weight loss numbers of any currently approved medication.

Clinical trial results:

  • SURMOUNT-1 trial: 2,539 adults without diabetes lost 16.0% (5 mg), 21.4% (10 mg), and 22.5% (15 mg) of body weight over 72 weeks. More than half of participants on the highest dose lost 20% or more [2].
  • SURMOUNT-4 trial (continuation data): Participants who stayed on tirzepatide for 88 weeks lost 25.3% of body weight. Those switched to placebo regained substantially, showing that continued treatment is needed to maintain results [9].
  • SURMOUNT-5 trial (head-to-head): Tirzepatide beat semaglutide directly, producing 20.2% weight loss versus 13.7% for semaglutide over 72 weeks [10].
  • Pooled meta-analysis: Across trials, tirzepatide produced an average of 18.7% weight loss, with 56% of patients on the highest dose losing 20% or more [11].

Tirzepatide activates both GLP-1 and GIP receptors. GIP appears to improve fat metabolism, which may explain the additional weight loss beyond GLP-1 alone. Like semaglutide, it is dosed once weekly by injection. Approved for adults with a BMI of 30+, or 27+ with at least one weight-related condition.

Liraglutide (Saxenda)

Liraglutide was the first GLP-1 receptor agonist approved specifically for weight management. It requires daily injections and produces more moderate weight loss than semaglutide or tirzepatide, but it has the longest safety track record of the group.

Clinical trial results:

  • SCALE Obesity and Prediabetes trial: 3,731 patients lost an average of 8.0% of body weight over 56 weeks, compared to 2.6% with placebo. About 63% of patients lost at least 5%, and 33% lost more than 10% [12].
  • SCALE Diabetes trial: Patients with type 2 diabetes lost 6.0% of body weight at the 3.0 mg dose over 56 weeks [13].
  • STEP 8 comparison: When tested head-to-head against semaglutide, liraglutide produced roughly 40% less weight loss (6.4% vs. 15.8%) [6].

Liraglutide works through the same GLP-1 mechanism as semaglutide but has a shorter half-life, requiring daily dosing. Approved for adults with a BMI of 30+, or 27+ with at least one weight-related condition.

Emerging GLP-1 Peptides in Clinical Trials

None of these are FDA-approved for weight management yet, but several have produced striking results that could reshape treatment within the next few years.

Retatrutide

Retatrutide is a "triple agonist" hitting GLP-1, GIP, and glucagon receptors simultaneously. Glucagon receptor activation -- the key differentiator -- increases energy expenditure and promotes hepatic fat oxidation.

Phase 2 trial data (48 weeks):

  • The highest dose (12 mg) produced 24.2% mean weight loss at 48 weeks -- and participants had not yet reached a weight plateau when the study ended [14].
  • 100% of participants on the 8 mg and 12 mg doses lost at least 5% of body weight. On the 12 mg dose, 83% lost at least 15% [14].
  • Liver fat decreased by more than 80% at higher doses, with 9 out of 10 patients with fatty liver disease achieving normal liver fat levels [15].

Current status: Phase 3 trials (the TRIUMPH program) are underway, with results expected in 2025-2026. One caveat: Phase 2 trials are smaller (338 participants here) and often produce better results than Phase 3. The 24% number may come down.

Survodutide

Survodutide is a dual GLP-1/glucagon receptor agonist developed by Boehringer Ingelheim. It shares the glucagon receptor component with retatrutide but does not target GIP.

Phase 2 trial data (46 weeks):

  • The highest tested dose (4.8 mg) produced 14.9% weight loss from baseline [16].
  • Survodutide has shown particular promise for metabolic dysfunction-associated steatohepatitis (MASH), with significant improvements in liver inflammation and fibrosis [16].

Current status: Phase 3 trials are ongoing for both obesity and MASH indications.

Mazdutide

Mazdutide is another dual GLP-1/glucagon receptor agonist, developed by Innovent Biologics in partnership with Eli Lilly. Most of its clinical data comes from trials conducted in China.

Clinical data:

  • GLORY-1 trial (Phase 3): Doses of 4 mg and 6 mg produced clinically relevant weight reductions in Chinese adults with overweight or obesity over 32 weeks [17].
  • Phase 2 data: Body weight changes from baseline to week 24 ranged from -6.7% (3 mg) to -11.3% (6 mg), compared to +1.0% with placebo [17].
  • High-dose Phase 1: A 16 mg dose is being tested and showed encouraging preliminary weight loss with improved metabolic regulation [18].

Current status: Approved in China. Higher-dose formulations are in development, and global trials are ongoing.

CagriSema

CagriSema combines two peptides in one injection: cagrilintide (an amylin analog) and semaglutide (the GLP-1 agonist). Amylin promotes satiety and slows gastric emptying through a pathway distinct from GLP-1.

Phase 3 trial data (REDEFINE 1):

  • In 3,417 adults with overweight or obesity, CagriSema produced 22.7% mean weight loss at 68 weeks [19].
  • While this was a strong result, it fell short of Novo Nordisk's previously communicated 25% target, causing initial market disappointment [19].
  • The earlier Phase 2 trial had shown 15.6% weight loss with CagriSema versus 5.1% with semaglutide alone and 8.1% with cagrilintide alone, suggesting the combination is more than the sum of its parts [20].

Current status: Phase 3 trials are complete. Regulatory submissions are expected.

Orforglipron

Orforglipron is a small molecule (not a peptide) that activates the GLP-1 receptor and is taken as a daily pill. No injections, no cold-chain storage, and potentially lower manufacturing costs.

Phase 3 trial data (ATTAIN-1):

  • In 3,127 adults without diabetes, the highest dose (36 mg) produced 12.4% weight loss at 72 weeks. Lower doses achieved 7.8% and 9.3% [21].
  • Among patients with prediabetes, up to 91% on orforglipron achieved near-normal blood sugar levels [21].

Current status: Eli Lilly submitted orforglipron for FDA review in 2025, with self-pay pricing announced at $149-$399 per month. The 12.4% weight loss is meaningfully lower than injectable tirzepatide (20-22%) or semaglutide (15-17%), but the convenience of a pill is a trade-off many patients will accept.

Growth Hormone Pathway Peptides

These peptides work through the growth hormone axis rather than GLP-1. They raise GH and/or IGF-1 levels, which can influence body composition. The evidence base here is substantially thinner than for GLP-1 agonists.

Tesamorelin

Tesamorelin is the strongest entry in this category. It is an FDA-approved GHRH (growth hormone-releasing hormone) analog, though its approval is specifically for HIV-associated lipodystrophy -- not general obesity.

Clinical trial results:

  • Phase III trials in HIV patients showed 15-18% reduction in visceral adipose tissue over 26-52 weeks, without significant changes in subcutaneous fat or BMI [4].
  • Visceral fat decreased by an average of 34 cm² with tesamorelin versus an 8 cm² increase with placebo [22].
  • Liver fat decreased by 37% in patients with HIV-associated fatty liver disease [23].
  • Tesamorelin also improved muscle quality, increasing skeletal muscle area and density in patients who had significant visceral fat reductions [24].

Tesamorelin selectively targets visceral (belly) fat rather than producing overall weight loss. It will not match the 15-25% total body weight reductions seen with GLP-1 drugs. Its value lies in targeted visceral fat reduction -- particularly relevant for individuals with excess abdominal fat and its associated cardiometabolic risks. Using it for general fat loss outside HIV-associated lipodystrophy is off-label, but it is the only FDA-approved peptide in the GH pathway category.

AOD-9604

AOD-9604 is a synthetic fragment of human growth hormone (amino acids 176-191 with a tyrosine modification) designed to isolate GH's fat-burning activity from its growth-promoting and glucose-raising effects.

The evidence picture is disappointing:

  • Animal studies showed promising fat loss in genetically obese mice and rats, with increased fat oxidation and reduced lipogenesis [3].
  • One small clinical trial showed subjects lost an average of 2.6 kg over 12 weeks at a 1 mg daily dose, compared to 0.8 kg with placebo [25].
  • A larger 24-week trial of 536 subjects failed to show statistically significant weight loss versus placebo [25].
  • Development was terminated in 2007 after these disappointing results.
  • A safety review of six controlled trials (900+ participants) found AOD-9604 was well-tolerated with no effect on IGF-1 or glucose tolerance [26].

Bottom line: AOD-9604 has a good safety profile but failed to demonstrate meaningful fat loss in adequately powered human trials. It is not FDA-approved for any indication. Despite this, it remains widely sold by peptide clinics and compounding pharmacies, often with claims that overstate its evidence base.

Fragment 176-191

Fragment 176-191 is the parent compound from which AOD-9604 was derived. It consists of amino acids 176-191 of human growth hormone without AOD-9604's stabilizing tyrosine modification.

Evidence: Nearly all the human clinical data in this category was generated with AOD-9604, not with the unmodified Fragment 176-191 itself. The available evidence is almost entirely preclinical (cell culture and animal models). Fragment 176-191 showed lipolytic activity in laboratory settings, but these results did not translate to significant fat loss in the human trials that used the modified version (AOD-9604) [3].

Bottom line: Fragment 176-191 has weaker evidence than AOD-9604, which itself failed in human trials. There is no compelling clinical reason to choose this peptide for fat loss over compounds with actual human data.

CJC-1295 + Ipamorelin

CJC-1295 is a GHRH analog that produces sustained increases in growth hormone and IGF-1 levels. Ipamorelin is a selective ghrelin mimetic (growth hormone secretagogue) that triggers shorter GH pulses. The two are commonly combined in clinical practice.

What the research shows:

  • CJC-1295 increased mean GH levels by 2- to 10-fold for 6+ days after a single injection, and IGF-1 levels by 1.5- to 3-fold for 9-11 days [27].
  • Ipamorelin selectively stimulates GH release without affecting other pituitary hormones (prolactin, cortisol, FSH, LH), which is considered a favorable selectivity profile [28].
  • There are no published randomized controlled trials demonstrating that the CJC-1295/ipamorelin combination produces significant fat loss or body composition changes in healthy adults [27].

We know these peptides raise GH and IGF-1. What we lack is clinical evidence showing those hormone increases translate into measurable fat loss. The claims commonly made for this combination -- fat burning, lean mass retention, better sleep -- are extrapolated from general GH effects, not from direct evidence. Neither peptide is FDA-approved, and the FDA has flagged both for safety concerns in compounding contexts.

MK-677 (Ibutamoren)

MK-677 is an oral GH secretagogue that mimics ghrelin. Not technically a peptide, but it appears in every "peptides for fat loss" discussion.

What the research shows:

  • A 12-month randomized trial in 65 healthy older adults found MK-677 increased fat-free mass by 1.1 kg compared to a 0.5 kg decrease with placebo. However, total fat mass did not decrease, visceral fat did not change, and limb fat actually increased [29].
  • A 2-month study in obese subjects found increases in fat-free mass and a transient increase in basal metabolic rate (at 2 weeks, but not at 8 weeks). Total and visceral fat were not significantly changed [30].
  • MK-677 consistently impairs glucose homeostasis, with increases in fasting glucose and decreases in insulin sensitivity [29, 30].

Bottom line: MK-677 raises GH and IGF-1 and can increase lean mass, but it does not reduce fat mass in human studies. It may work against fat loss by increasing appetite (it mimics ghrelin, the "hunger hormone") and worsening insulin sensitivity. Not FDA-approved; banned in sport by WADA.

Comparing Fat Loss Peptides

PeptideMechanismMean Weight LossTrial DurationFDA StatusEvidence Level
Tirzepatide 15 mgGLP-1/GIP dual agonist20.2-22.5%72 weeksApproved (Zepbound)Phase 3, 2,500+ patients
Semaglutide 2.4 mgGLP-1 agonist14.9-17.4%68 weeksApproved (Wegovy)Phase 3, 1,900+ patients
Semaglutide 7.2 mgGLP-1 agonist20.7%72 weeksUnder reviewPhase 3
Retatrutide 12 mgGLP-1/GIP/glucagon triple agonist24.2%48 weeksInvestigationalPhase 2 (Phase 3 ongoing)
CagriSemaGLP-1 + amylin analog22.7%68 weeksInvestigationalPhase 3, 3,400+ patients
Survodutide 4.8 mgGLP-1/glucagon dual agonist14.9%46 weeksInvestigationalPhase 2 (Phase 3 ongoing)
Orforglipron 36 mgOral GLP-1 agonist12.4%72 weeksUnder reviewPhase 3, 3,100+ patients
Liraglutide 3.0 mgGLP-1 agonist8.0%56 weeksApproved (Saxenda)Phase 3, 3,700+ patients
Mazdutide 6 mgGLP-1/glucagon dual agonist11.3% (24 wks)24-32 weeksApproved (China)Phase 2-3
TesamorelinGHRH analog15-18% visceral fat only26-52 weeksApproved (HIV lipodystrophy)Phase 3
AOD-9604HGH fragmentFailed in Phase 2b24 weeksNot approvedDevelopment terminated
CJC-1295 + IpamorelinGHRH analog + GH secretagogueNo fat loss dataN/ANot approvedNo body composition RCTs
MK-677Oral GH secretagogueNo fat reduction12 monthsNot approvedNo fat loss demonstrated
Fragment 176-191HGH fragmentNo human dataN/ANot approvedPreclinical only

The pattern is clear: GLP-1-based therapies dominate on both efficacy and evidence quality.

Safety Considerations

GI side effects are the signature of GLP-1 therapy. Nausea, vomiting, diarrhea, and constipation are the most common adverse events. These are typically mild to moderate, peak during dose escalation, and decrease over time. In SURMOUNT-1, GI events led 4-7% of participants to discontinue; rates were similar for semaglutide in STEP 1 [1, 2].

Lean mass loss is real but manageable. With GLP-1 therapies, lean mass can account for 25-40% of total weight lost. In STEP 1, semaglutide reduced lean mass by about 6.9 kg alongside 15.3 kg of total weight loss [31]. Tirzepatide showed a better ratio, with lean mass at roughly 26% of total weight lost [31]. Resistance training combined with adequate protein (1.0-1.2 g/kg/day) can significantly reduce lean mass loss [32]. See our guide on best peptides for muscle growth for more.

Long-term data is still accumulating. The SELECT trial provides 4-year data for semaglutide [8], but newer compounds have 68-72 weeks at most. Questions about decades-long use remain open.

Weight regain after stopping is expected. The SURMOUNT-4 trial showed substantial regain after switching from tirzepatide to placebo [9]. These medications manage a chronic condition -- stopping treatment generally means the condition returns.

Growth hormone pathway peptides carry different risks. Tesamorelin carries a warning about use in patients with active malignancy due to elevated GH/IGF-1 signaling [4]. MK-677 worsens insulin sensitivity [29, 30]. CJC-1295 and ipamorelin have less-characterized long-term safety profiles, and the unregulated nature of compounded peptides introduces risks around purity, potency, and sterility.

Sourcing matters enormously. FDA-approved medications are manufactured under strict regulatory standards. Compounded and research-grade peptides sold online often lack the same quality assurance. The FDA has warned that unregulated peptide products may contain harmful ingredients, incorrect doses, or no active ingredient at all.

Frequently Asked Questions

What is the most effective peptide for fat loss?

Tirzepatide (Zepbound) produces the highest weight loss among FDA-approved treatments: 20-22% of body weight in clinical trials. Among investigational compounds, retatrutide showed up to 24% in Phase 2, though this needs Phase 3 confirmation. Both require a prescription.

Do growth hormone peptides like CJC-1295 and ipamorelin help with fat loss?

These peptides raise GH and IGF-1, but no randomized controlled trials show they produce significant fat loss in humans. Tesamorelin is the exception -- it has Phase 3 data showing 15-18% visceral fat reduction, though it is approved only for HIV-associated lipodystrophy.

Can I take peptides for fat loss without a prescription?

FDA-approved GLP-1 agonists require a prescription. Non-approved peptides like AOD-9604, CJC-1295, and ipamorelin are sometimes obtained through compounding pharmacies or research vendors, but the FDA does not regulate these products for safety or quality. You cannot be certain of what you are injecting.

How much weight can I expect to lose on GLP-1 peptides?

Average weight loss ranges from about 8% (liraglutide) to 22% (tirzepatide at the highest dose) over 56-72 weeks. Individual results vary widely -- some trial participants lost 25-30% while others lost less than 5%. Starting weight, dose, diet, exercise, and genetics all matter.

Will I lose muscle mass on GLP-1 medications?

Some lean mass loss occurs with any significant weight loss. With GLP-1 therapies, lean mass can account for 25-40% of total weight lost. Resistance training and protein intake of 1.0-1.2 g/kg/day can substantially reduce this. A trial combining semaglutide with bimagrumab showed 92.8% of weight loss came from fat, compared to 71.8% with semaglutide alone [32]. See our best peptides for muscle growth and athletic performance guides for more.

Is AOD-9604 worth trying for fat loss?

No. The 24-week Phase 2b trial of 536 subjects failed to show statistically significant weight loss versus placebo. Development was terminated in 2007. Despite this, it continues to be marketed by peptide clinics.

Do I have to inject, or are there oral options?

Orforglipron, an oral GLP-1 agonist under FDA review, showed 12.4% weight loss as a daily pill. It is less effective than injectable options but removes the injection barrier. Oral semaglutide (Rybelsus) is already approved for type 2 diabetes, and higher-dose oral semaglutide for obesity is in development.

How long do I need to take peptides for fat loss?

Current evidence suggests GLP-1 medications are long-term treatments. When participants stop taking them in trials, weight regain is the norm. Whether lower maintenance doses can sustain weight loss is an active area of research.

The Bottom Line

The evidence hierarchy for fat loss peptides is steep and unambiguous.

At the top: FDA-approved GLP-1 agonists tirzepatide and semaglutide, with 15-22% weight loss across large trials and well-characterized safety profiles. The December 2025 WHO guideline on GLP-1 therapies for obesity -- the organization's first -- reflects the strength of this evidence [33].

Below that: investigational compounds like retatrutide, CagriSema, and orforglipron, with strong Phase 2-3 data that may bring even better results or more convenient delivery soon.

Then a large drop-off. Tesamorelin has solid evidence for visceral fat reduction in a specific population. Every other GH pathway peptide in this guide -- AOD-9604, Fragment 176-191, CJC-1295, ipamorelin, MK-677 -- either failed in human trials or has never been properly tested for fat loss in humans.

If you are considering peptides for fat loss, start with the evidence. Talk to a physician about FDA-approved options. Be skeptical of compounds marketed on animal studies, elevated biomarkers, or testimonials. The science of obesity treatment has advanced enormously -- but only for the compounds that have actually been through the scientific process.

This article is for educational purposes only and does not constitute medical advice. Peptide therapies should only be used under the supervision of a qualified healthcare provider. Do not start, stop, or change any medication without consulting your doctor.

References

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