The Best Peptides for Weight Loss: What Physicians Actually Prescribe

Body weight is defended by a control system. Hormones from the gut, the pancreas and fat tissue report to the hypothalamus and brainstem, which adjust hunger, fullness and energy expenditure to hold weight in a range. When intake falls, ghrelin rises, leptin falls, and the drive to eat increases. Diets that rely on tolerating hunger produce short-term loss and long-term regain because the system is doing what it is built to do.

GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) are released from the intestine when food arrives. They are why a meal produces a larger insulin response than the same glucose given intravenously, and GLP-1 also slows gastric emptying and acts on appetite centers in the brain. Native GLP-1 is broken down within minutes by the enzyme DPP-4; the medications with real evidence are analogs engineered to survive for days.

Fat inside the abdomen around the organs (visceral fat) is more metabolically active and more inflammatory than fat under the skin, and more closely tied to insulin resistance, fatty liver and cardiovascular risk. Growth hormone secretion falls with age and with obesity, and reduced growth hormone is associated with visceral fat accumulation. That is the rationale for tesamorelin, which acts on the growth hormone axis rather than on appetite.

Losing weight lowers resting energy expenditure, partly because a smaller body costs less to run and partly because some of the loss is lean tissue. Lose muscle alongside fat and you finish lighter but with a lower baseline burn, the mechanism behind regain. It is why lean mass is part of the prescription, and the honest rationale for the growth-hormone-axis and mitochondrial peptides that appear here as adjuncts.

Semaglutide is a GLP-1 receptor agonist modified to bind albumin and resist DPP-4, which gives it a half-life long enough for once-weekly injection. It prompts insulin release only when blood glucose is high, suppresses glucagon, slows gastric emptying, and acts on appetite centers in the brain, the effect patients describe as the noise around food going quiet.

STEP 1 (New England Journal of Medicine, 2021) randomized 1,961 adults with overweight or obesity to weekly semaglutide 2.4 mg or placebo for 68 weeks; the semaglutide group lost a mean of 14.9% of body weight against 2.4% on placebo. STEP 2 (The Lancet, 2021) repeated this in type 2 diabetes, STEP 5 (Nature Medicine, 2022) held the result over two years, and STEP 8 (JAMA, 2022) put it well ahead of daily liraglutide. SELECT (New England Journal of Medicine, 2023), in more than 17,000 adults with overweight or obesity and established cardiovascular disease, reported a 20% relative reduction in major adverse cardiovascular events.

Compounded semaglutide contains the same active ingredient as the branded product, not its approval; see is compounded semaglutide safe. It suits someone with meaningful weight to lose who is prepared to titrate slowly.

Tirzepatide is a dual agonist at the GIP receptor as well as the GLP-1 receptor; the GIP arm adds separate effects on insulin secretion and on how fat tissue handles nutrients. Which of the two suits you is set out in semaglutide vs tirzepatide. The compounded preparation also contains cyanocobalamin, a form of vitamin B12.

SURMOUNT-1 (New England Journal of Medicine, 2022) randomized 2,539 adults with obesity to tirzepatide 5, 10 or 15 mg weekly or placebo for 72 weeks; the highest dose produced a mean loss of 20.9% against 3.1%. SURMOUNT-2 (The Lancet, 2023) repeated this in type 2 diabetes, SURMOUNT-5 (New England Journal of Medicine, 2025) showed significantly greater loss than semaglutide 2.4 mg head to head, and SURMOUNT-OSA (New England Journal of Medicine, 2024) reported reduced obstructive sleep apnea severity. Compounded tirzepatide suits someone who wants the dual-receptor option, has a lot of weight to lose, or did not respond adequately to semaglutide.

These are dispensed as dose-specific vials, and the active ingredient is the largest cost. A prescriber starts low and steps up over weeks, because tolerance builds and because starting high is the surest way to make someone quit in month one.

Your physician sets the strength and the pace. Current figures are at /cost/semaglutide and /cost/tirzepatide.

Tesamorelin is a synthetic analog of growth hormone-releasing hormone. It acts on the pituitary to increase the body's own pulsatile growth hormone secretion, raising IGF-1 and lipolysis, with visceral fat the tissue most affected. It does not act on appetite.

In the New England Journal of Medicine in 2007, tesamorelin reduced visceral adipose tissue over 26 weeks in HIV-infected patients with abdominal fat accumulation, against an increase on placebo, with liver-fat trials in JAMA (2014) and Lancet HIV (2019) following. The most relevant trial for a general patient is Makimura's randomized controlled trial (Journal of Clinical Endocrinology and Metabolism, 2012) in obese adults with reduced growth hormone secretion and no HIV: visceral fat area fell against placebo over twelve months while body weight did not meaningfully change.

That last clause is the honest framing. The approved product's own label states it is not indicated for weight loss management because it has a weight-neutral effect. Tesamorelin is prescribed for where fat sits, not how much there is. The product page directions are once daily by subcutaneous injection; your physician sets the dose.

AOD-9604 is a synthetic fragment of the C-terminal region of human growth hormone (amino acids 177 to 191) with an added tyrosine, designed to keep the lipolytic region without the growth and glucose effects. In obese mice, Endocrinology in 2001 and the International Journal of Obesity in 2001 reported increased fat oxidation and reduced weight gain.

The human story has to be told carefully. The FDA's 2024 briefing document for its advisory committee summarized the developer's phase 2b OPTIONS trial: 536 adults with obesity enrolled, oral AOD-9604 or placebo daily for 24 weeks alongside a supervised diet and exercise program; there was no significant difference in weight loss between AOD-9604 and placebo on the primary endpoint. AOD-9604 appears in PHYSIQ and SHRED and on its own as AOD-9604. Anyone selling it as a fat-loss agent is ignoring the trial that tested exactly that; a physician uses it as one component of a body-composition blend alongside training.

MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA rather than the nuclear genome. In Cell Metabolism in 2015, treatment prevented diet-induced obesity and insulin resistance in mice through AMPK signaling in skeletal muscle; Nature Communications in 2021 described it as an exercise-induced peptide whose levels rise with activity in humans, with improved physical capacity in old mice given the peptide. Human data are observational only.

There are no randomized human trials of injected MOTS-c; the FDA's July 2026 review for its advisory committee stated it did not identify any clinical studies or human exposure data for the peptide. MOTS-c is in PHYSIQ, SHRED and FUSION and on its own as MOTS-c, a mitochondrial adjunct alongside training.

5-Amino-1MQ is not a peptide. It is a small molecule that inhibits nicotinamide N-methyltransferase (NNMT), an enzyme upregulated in the fat tissue of people with obesity and insulin resistance (Diabetologia, 2015). Knocking the enzyme down protected mice from diet-induced obesity in Nature in 2014, and the inhibitor reversed diet-induced obesity in mice in Biochemical Pharmacology in 2018; the described mechanism is raising intracellular NAD+ and shifting adipocytes toward energy expenditure. There are no randomized human trials of 5-Amino-1MQ. It is available as 5-Amino-1MQ and inside FUSION, as a metabolic adjunct, never as the answer to meaningful excess weight on its own.

SLU-PP-332 is also a small molecule: a synthetic agonist of the estrogen-related receptors, transcription factors governing mitochondrial biogenesis and oxidative metabolism in muscle. ACS Chemical Biology in 2023 reported an aerobic-exercise-like gene expression pattern and enhanced exercise capacity in mice, and the Journal of Pharmacology and Experimental Therapeutics in 2024 reported increased energy expenditure in a mouse model of metabolic syndrome. There are no randomized human trials of SLU-PP-332, and two 2026 papers characterize its metabolites for doping control, which tells you what class of compound it is. It is available as SLU-PP-332 for someone training seriously who is not a tested athlete.

Adipotide is a peptidomimetic that homes to the blood vessels supplying white fat and triggers programmed cell death there, cutting supply to the tissue rather than acting on appetite. Nature Medicine in 2004 reported reversal of obesity in mice, and Science Translational Medicine in 2011 reported weight loss and improved insulin resistance in obese rhesus monkeys over four weeks, with a dose-dependent, reversible effect on kidney function. There are no published randomized human trials of adipotide. The renal signal is why it is not in routine use and why kidney function is a hard question first; it is available as adipotide for the narrow set of patients whose physician judges it appropriate.

PHYSIQ combines tesamorelin, ipamorelin, AOD-9604 and MOTS-c; SHRED combines AOD-9604, CJC-1295, ipamorelin and MOTS-c; FUSION combines BPC-157, MOTS-c, 5-Amino-1MQ and tesamorelin. Each puts three or four agents into one injection. They are body-composition products used alongside training, and no serious prescriber offers them instead of a GLP-1 where real weight loss is the goal. The evidence for a blend is the evidence for its parts, including CJC-1295's human pharmacology (sustained growth hormone and IGF-1 in healthy adults, Journal of Clinical Endocrinology and Metabolism, 2006) and ipamorelin's selectivity work (European Journal of Endocrinology, 1998).

In the STEP 1 extension (Diabetes, Obesity and Metabolism, 2022), participants regained about two-thirds of their lost weight in the year after semaglutide was stopped, and the cardiometabolic improvements largely reversed with it. SURMOUNT-4 (JAMA, 2024) showed the same for tirzepatide: after 36 weeks of open-label treatment, those switched to placebo regained a large share of what they had lost while those who continued kept losing. This is not a failure of the drug; it is the appetite control system returning to its set point once the signal is removed, and it is why treatment is long-term with 28-day refills. See what happens when you stop taking peptides.

Weight lost on a GLP-1 is not all fat. In the STEP 1 body-composition substudy, both fat mass and lean mass fell, though fat fell by more and the proportion of lean mass rose. At this level of appetite suppression most people eat far less protein than they realize. Losing muscle alongside fat leaves you lighter, weaker and with a lower resting metabolic rate, the mechanism behind regain. Four things belong in the prescription, not a footnote:

Some prescribers add a growth-hormone-axis peptide such as CJC-1295 / Ipamorelin or tesamorelin alongside a GLP-1 with lean tissue in mind, as an adjunct to training and protein rather than a replacement; no trial shows that a growth hormone secretagogue preserves lean mass during GLP-1 treatment. Nausea is the most common reason people stop early, and GLP-1 nausea: how to manage it covers what helps.

• That any adjunct on this page adds weight loss on top of a GLP-1. No trial has tested that combination.
• An effect size for MOTS-c, 5-Amino-1MQ, SLU-PP-332 or adipotide in people. Those trials have not been run.
• Long-term safety over years for the adjuncts, which is one reason a physician reviews them at each refill.
• Efficacy for any compounded product as an FDA-approved treatment. Compounded medications are not FDA approved.

Both have approved reference products: semaglutide as Ozempic, Rybelsus and Wegovy, tirzepatide as Mounjaro and Zepbound. Both were on the FDA's drug shortage list from 2022, and while a drug is in shortage federal law allows compounding pharmacies to prepare it. The FDA determined the tirzepatide shortage resolved on 19 December 2024, with 503A pharmacies given until 18 February 2025 and 503B outsourcing facilities until 19 March 2025 to stop compounding copies, and the semaglutide shortage resolved on 21 February 2025, with 503A pharmacies given until 22 April 2025 and 503B facilities until 22 May 2025.

Shortage-based compounding has ended. What remains is the ordinary 503A pathway: a state-licensed pharmacy may compound for an identified patient where the prescriber has determined that the compounded product differs from the commercial one in a way that produces a significant difference for that patient. On 30 April 2026 the FDA proposed to exclude semaglutide, tirzepatide and liraglutide from the 503B bulks list; that is a proposal about outsourcing facilities, not a final rule. The FDA's page on unapproved GLP-1 products, current as of 1 September 2026, warns that some compounders sold salt forms (semaglutide sodium, semaglutide acetate), which it treats as different active ingredients from the approved drug, so ask any provider which form their pharmacy dispenses.

An FDA-approved tesamorelin product exists. Egrifta was approved on 10 November 2010, and the current formulation, Egrifta WR, on 25 March 2025, both for the reduction of excess abdominal fat in HIV-infected adults with lipodystrophy. Because tesamorelin is the active ingredient of an approved drug, it was never nominated for the 503A bulk substances list and appears in none of its categories. Compounded tesamorelin, at a different strength or in a blend, is not FDA approved.

AOD-9604 was placed in Category 2 of the FDA's interim 503A bulk drug substances list in 2023, the category for nominated substances flagged as raising significant safety concerns. It left that category when its nominations were withdrawn; the FDA's safety-risks page, current as of 22 April 2026, lists it under substances nominated but withdrawn, alongside CJC-1295, ipamorelin acetate, BPC-157 and MOTS-c. On 4 December 2024 the FDA's Pharmacy Compounding Advisory Committee voted 0 in favor and 12 against adding AOD-9604 to the 503A Bulks List, having evaluated it for obesity, and 0 to 13 on CJC-1295. On 29 October 2024 it voted 0 in favor, 12 against, with 1 abstention, on ipamorelin, evaluated for growth hormone deficiency and postoperative ileus. Those are advisory recommendations; the FDA has not issued a final determination, and none of the three appears in Category 1, 2 or 3 of the interim list updated 14 May 2026.

MOTS-c was placed in Category 2 in 2023. On 15 April 2026 the FDA announced the removal of twelve peptides from Category 2, effective about a week later, and MOTS-c was among them, alongside BPC-157, KPV and TB-500. The FDA was explicit that removal does not by itself place a substance on the 503A Bulks List. On 23 July 2026 the Pharmacy Compounding Advisory Committee reviewed MOTS-c for obesity and osteoporosis and voted 7 in favor, 5 against, with 2 abstentions, to recommend adding it to the 503A Bulks List; BPC-157, a FUSION component, was recommended 8 to 6 the same day. A recommendation is not a rule; the FDA's final determination is pending.

None of the three appears in any category of the FDA's interim 503A list updated 14 May 2026, none was ever in Category 2, and none was on the agenda when the advisory committee met on 23 and 24 July 2026. None is a component of an approved drug. They are prescribed under the ordinary 503A framework, and a physician weighs the thinner regulatory record when deciding whether one is appropriate.

The WADA Prohibited List in force is the 2026 List, effective 1 January 2026. Growth hormone releasing factors and secretagogues (tesamorelin, CJC-1295, ipamorelin) and growth hormone fragments are prohibited at all times; the anti-doping literature describes AOD-9604 as banned by WADA and published a urine detection method for it (Drug Testing and Analysis, 2015). SLU-PP-332 falls under WADA's prohibition of exercise mimetics and metabolic modulators, with detection methods published in 2026, and a validated plasma test for MOTS-c exists (Rapid Communications in Mass Spectrometry, 2019). GLP-1 receptor agonists are not among the prohibited classes, but a tested athlete should confirm their own medication on Global DRO and tell their physician before starting anything on this page.

The starting dose is deliberately low and is not the dose that produces most of the weight loss. What most people notice first is appetite: smaller portions feel like enough, snacking drops away, and food is less present in the mind. Nausea, if it comes, tends to arrive in the days after each dose increase and to settle. Weight change in this window is modest and is not the measure of whether the medication is working.

Doses step up roughly every four weeks as tolerated, which is why refills run on a 28-day rhythm and why one vial per fill is the rule. In the trials, most of the weight loss accrued steadily across the first year rather than in a burst. A prescriber who moves you up faster than you tolerate is trading a month of nausea for nothing.

Every trial curve flattens, typically well into the second half of the first year, as the body adapts and the new intake meets the new expenditure. A plateau is not a sign to stop; it is the point at which protein, resistance training and the dose are reviewed. Why am I not losing weight on semaglutide exists because this is ordinary. Tesamorelin's visceral fat effect was measured by imaging, not on a scale, so look at waist measurement rather than weight. What prescribers describe for the blends and single adjuncts is change in body composition over months alongside training; nobody can give you a number for MOTS-c, 5-Amino-1MQ or SLU-PP-332 because the human trial that would produce one has not been run.

Appetite returns when a GLP-1 stops, and the withdrawal trials show what follows. Treatment is long-term, on 28-day refills, with the dose adjusted by your physician as your weight and tolerance change. The people who keep the result are the ones who built eating and training habits while the medication made that easier.

Commonly: thyroid function, fasting glucose or HbA1c, a metabolic panel including kidney and liver function, and lipids. For tesamorelin, a baseline IGF-1. For adipotide, kidney function is non-negotiable. At-home blood testing covers the markers without a lab visit; your physician decides what is needed.

A GLP-1 is reviewed at each 28-day refill: weight, tolerance, hydration, and whether the dose moves. HbA1c and lipids are typically repeated after several months because they are the markers that improve. Tesamorelin's label calls for monitoring IGF-1 during treatment, considering stopping if it stays persistently high, and watching glucose. For the blends and single adjuncts, a physician repeats the metabolic panel periodically because there is no trial-derived monitoring schedule to lean on.

Severe or persistent abdominal pain, vomiting that stops you keeping fluids down, signs of gallbladder disease, a lump in the neck or trouble swallowing, symptoms of low blood sugar if you also take insulin or a sulfonylurea, and any reaction that is severe, spreading or involves difficulty breathing. Your physician stays reachable for exactly these.