Direct Answers, Cited Where They Need To Be

What is semaglutide?

Semaglutide (Ozempic, Wegovy, Rybelsus) is a 31-amino-acid acylated analogue of human glucagon-like peptide-1 (GLP-1), sharing roughly 94% sequence homology with the natural hormone. Structurally it differs from native GLP-1 in three ways that matter: an alpha-aminoisobutyric acid substitution at position 8 blocks the enzyme dipeptidyl peptidase-4 from cleaving it, an arginine substitution at position 34 leaves a single free lysine, and a C18 fatty di-acid side chain attached at that lysine binds serum albumin and shields the peptide from renal clearance. Those changes take a hormone that survives about two minutes and give it a half-life of roughly a week.

It is an approved prescription medicine, available as a once-weekly subcutaneous injection — marketed as Ozempic and as Wegovy — and as a once-daily oral tablet, marketed as Rybelsus. Full briefing: semaglutide.

Is Ozempic the same as semaglutide?

Yes, in the sense that matters here: Ozempic is a brand name for a product whose active ingredient is semaglutide. So are Wegovy and Rybelsus. The peptide is identical in all three.

What differs is the wrapper. Ozempic and Wegovy are subcutaneous injections; Rybelsus is an oral tablet, co-formulated with an absorption enhancer because the peptide is otherwise very poorly absorbed from the gut. The brands also carry different approved indications — broadly, the diabetes indications on one side and the chronic weight management and cardiovascular risk reduction indications on the other — and different approved strength ranges.

This matters when reading research. The trial literature reports the drug name, not the brand: the 68-week weight trial ^[4], the cardiovascular outcomes trial in 17,604 participants ^[3] and the kidney trial in 3,533 participants ^[2] are all semaglutide trials, and this site reports them that way.

Which product, if any, suits a given person is a prescribing decision and not one a website can make.

What is semaglutide used for?

It is approved across four indications: type 2 diabetes mellitus; chronic weight management; reduction of major adverse cardiovascular events in adults with established cardiovascular disease and overweight or obesity; and metabolic dysfunction-associated steatohepatitis.

The cardiovascular indication rests on a trial of 17,604 adults with established cardiovascular disease and a body-mass index of 27 or above but without diabetes, in which the once-weekly 2.4 mg study arm reduced the composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke with a hazard ratio of 0.80 (95% CI 0.72–0.90; P<0.001) ^[3]. A separate trial in 3,533 people with type 2 diabetes and chronic kidney disease reported a hazard ratio of 0.76 (95% CI 0.66–0.88) for major kidney-disease events ^[2].

This site does not advise on whether any of those indications applies to a given person. That is a clinical judgement.

How does semaglutide work?

It activates the GLP-1 receptor, and the effects split three ways.

In the pancreas, it potentiates glucose-dependent insulin secretion from beta cells and suppresses glucagon release from alpha cells. Glucose-dependent is the operative word: the insulin response scales with circulating glucose, which is why the compound does not on its own drive blood sugar below normal the way an insulin secretagogue can.

In the gut, it slows gastric emptying, blunting the post-meal glucose rise and prolonging fullness. This is also the origin of most of its tolerability problems — the nausea is downstream of the mechanism, not incidental to it.

In the brain, it reaches hypothalamic and brainstem appetite circuits. That is where the weight effect lives, and it is covered separately below.

How does semaglutide work for weight loss?

Primarily centrally, and by reducing intake rather than raising expenditure.

Semaglutide reaches appetite circuits in the hypothalamic arcuate nucleus and in the brainstem area postrema and parabrachial nucleus. There it activates anorexigenic POMC/CART neurons — the ones signalling satiety — and inhibits orexigenic NPY/AgRP neurons, the ones driving hunger. The result is reduced food intake and a shift in food preference. Slowed gastric emptying contributes by prolonging fullness after a meal.

Critically, it does this without increasing energy expenditure. The weight change is an intake effect. In the STEP 1 randomised trial of 1,961 adults with overweight or obesity and without diabetes, the once-weekly 2.4 mg study arm produced a mean body-weight change of -14.9% at week 68 against -2.4% on placebo ^[4].

What is tirzepatide?

Tirzepatide (Mounjaro, Zepbound) is a linear 39-amino-acid synthetic peptide, built on the native GIP sequence rather than the GLP-1 one, with a C20 fatty diacid attached through a glutamic acid linker and two (2-(2-aminoethoxy)ethoxy)acetic acid units to a lysine side chain. Molecular formula C225H348N48O68. The fatty-diacid arm confers albumin affinity and a half-life permitting once-weekly administration.

It is the first approved dual incretin agonist — one molecule engaging both the GIP and the GLP-1 receptor ^[6]. In the literature it is sometimes called a twincretin; its development code was LY3298176.

It is the lead compound on this desk, because it is the only one here that has beaten the class benchmark in a direct head-to-head randomised trial rather than against placebo ^[1]. Full briefing: tirzepatide.

What is the difference between Mounjaro and Zepbound?

Pharmacologically, none. Both products contain tirzepatide — the same 39-amino-acid dual GIP and GLP-1 receptor agonist, the same mechanism, the same trial programme behind them.

The difference is regulatory. The two brand names correspond to different approved indications: the type 2 diabetes indication, first granted in May 2022 ^[6], is marketed as Mounjaro, while the chronic weight management indication and the moderate-to-severe obstructive sleep apnoea indication are marketed as Zepbound. A manufacturer registers a separate brand per indication, which is a commercial and labelling convention rather than a statement about the molecule.

The practical consequence for a reader is simply that the research is not split the way the brands are. The 72-week trial in 2,539 adults with obesity ^[8] and the 40-week trial in 1,879 adults with type 2 diabetes ^[9] both studied tirzepatide, and both appear on the tirzepatide briefing rather than under one brand or the other.

Which product applies to a given person depends on the indication being treated, and that is a clinical determination.

How does tirzepatide work?

By agonising two incretin receptors at once — but not equally, and that asymmetry is the interesting part.

In vitro receptor-occupancy and signalling assays established that tirzepatide is an imbalanced dual agonist: it engages the GIP receptor to a greater degree than the GLP-1 receptor. At the GLP-1 receptor it also shows biased signalling, favouring cAMP generation over beta-arrestin recruitment, with weaker receptor internalisation than native GLP-1 produces ^[10].

That bias has a plausible functional payoff. Beta-arrestin recruitment is one route by which a receptor is desensitised. In primary islet experiments, beta-arrestin1 limited the insulin response to GLP-1 but not the response to GIP or to tirzepatide ^[10] — which is the proposed basis for a more sustained insulin-secretory signal than an unbiased GLP-1 agonist can maintain.

What does tirzepatide do in the body?

Four things, all downstream of dual receptor engagement.

It enhances glucose-dependent insulin secretion from pancreatic beta cells. It suppresses glucagon, the hormone that raises blood glucose. It slows gastric emptying, which blunts post-meal glucose rises and prolongs fullness. And it reduces appetite and food intake through central mechanisms.

The combination produces larger glycaemic and weight effects than selective GLP-1 receptor agonism alone. In a 40-week trial of 1,879 adults with type 2 diabetes, the three study arms reduced glycated haemoglobin by an estimated 2.01, 2.24 and 2.30 percentage points respectively against 1.86 percentage points with semaglutide 1 mg, and produced greater weight reductions with treatment differences of -1.9 kg, -3.6 kg and -5.5 kg ^[9].

It also slows the absorption of some co-administered oral medicines, which is a labelled interaction rather than a side effect.

What is tirzepatide used for?

It was first approved in May 2022 for type 2 diabetes mellitus ^[6]. Subsequent approvals extended it to chronic weight management in adults with obesity, or overweight with a weight-related condition, and to moderate-to-severe obstructive sleep apnoea in adults with obesity. It is not approved for type 1 diabetes ^[6], and all approved formulations are prescription-only.

The obesity evidence comes from a 72-week phase 3 trial in 2,539 adults without diabetes, where mean weight change reached -20.9% in the highest study arm against -3.1% on placebo ^[8], and from the head-to-head trial in 751 adults where it reported -20.2% against semaglutide's -13.7% (P<0.001) ^[1].

Whether it is appropriate for any individual is a clinical decision this site does not make.

What does retatrutide do?

It agonises three receptors at once — GIP, GLP-1 and glucagon — and the third one is what makes it different in kind rather than merely in degree.

The GLP-1 and GIP arms suppress appetite and improve glucose-dependent insulin secretion, the same job the approved incretins do. Controlled glucagon-receptor activation adds increased energy expenditure and lipid mobilisation. Where the other incretin compounds reduce weight purely by reducing intake, this one has a second lever.

In a 48-week phase 2 trial of 338 adults with obesity, the highest study arm produced a mean body-weight change of -24.2% against -2.1% on placebo ^[15]. A phase 2 liver substudy in 98 participants reported relative liver-fat reductions reaching -82.4% at 24 weeks, with 86% reaching normal liver fat ^[14].

It also produces a dose-dependent increase in resting heart rate, peaking around 24 weeks ^[15].

How does retatrutide work?

Through triple receptor agonism with a deliberately uneven potency profile.

Cryo-electron-microscopy structures resolved retatrutide bound to GLP-1R, GIPR and GCGR at 2.68, 3.26 and 2.84 ångström respectively. cAMP signalling assays put it at roughly 8.9 times the potency of native GIP at the GIP receptor, but only 0.3 times and 0.4 times the potency of the endogenous hormones at the glucagon and GLP-1 receptors ^[13]. The same work found extracellular loop 1 adopts a rigid alpha-helix in GLP-1R and GCGR but a flexible loop in GIPR.

The weak glucagon arm is design rather than deficiency. Glucagon raises blood glucose; a triple agonist with full glucagon potency would be a considerably more dangerous molecule. The incretin arms hold the glycaemic consequence in check while the glucagon arm contributes thermogenesis.

How to reconstitute retatrutide?

This site does not publish reconstitution, preparation, handling or administration procedures for any compound, and it will not make an exception here.

The reason is specific rather than squeamish. Retatrutide is investigational: it has been approved by no regulator, it exists as a supervised trial product only, and there is no approved prescribing information from which a handling procedure could legitimately be drawn ^[12]. Any material circulating outside a clinical trial is of unverified identity, purity and sterility. Independent analyses of comparable gray-market peptides have found truncated sequences, racemised amino acids, and entirely different compounds; without sterility and endotoxin testing, injectable contamination risk includes sepsis. Regulators have issued warning letters to vendors selling it.

Publishing a procedure would imply the underlying material is characterised. It is not. Every figure on the retatrutide briefing describes a supervised trial product, and none of it transfers.

Is retatrutide FDA approved?

No. Retatrutide is investigational, and it has not been approved by the FDA or by any other regulator.

It is in phase 3 trials. There is no approved indication, no prescribing information, and no prescription or consumer product. Every efficacy and safety figure published about it comes from clinical trials rather than approved labelling: a 48-week phase 2 obesity trial in 338 adults ^[15], a 36-week phase 2 diabetes trial in 281 adults ^[16], and a phase 2 liver-fat substudy in 98 participants ^[14]. A 2025 review characterises the up-to-24% weight loss over 48 weeks as a step change against prior incretin therapies while noting the phase 3 programme is ongoing ^[12].

What does not exist: any completed head-to-head trial against an approved agent, any cardiovascular or kidney outcome result, and any long-term safety data.

What is tesamorelin?

Tesamorelin (Egrifta) is a synthetic 44-amino-acid analogue of human growth hormone-releasing hormone — GHRH(1-44)-NH2 — with a trans-3-hexenoic acid group conjugated to the N-terminus. That modification blocks cleavage by dipeptidyl peptidase-IV and extends plasma stability relative to the native hormone. Empirical formula of the free base C221H366N72O67S; supplied clinically as the acetate salt. Its development code was TH9507.

It is the only compound on this desk that is not an incretin drug. It was approved in the United States in November 2010 to reduce excess abdominal fat in adults with HIV-associated lipodystrophy ^[18], and it has no approved indication outside that one.

It is also prohibited in sport under WADA category S2, in and out of competition. Full briefing: tesamorelin.

Is Egrifta the same as tesamorelin?

Yes. Egrifta is the brand name under which tesamorelin is marketed; the active ingredient is the same synthetic GHRH(1-44) analogue.

Unlike semaglutide and tirzepatide, which each carry several brand names because each carries several approved indications, tesamorelin has one brand name because it has one approved indication: reduction of excess abdominal fat in adults with HIV-associated lipodystrophy, approved in the United States in November 2010 ^[18].

That one-to-one mapping is worth noticing rather than skipping. It means anything described as tesamorelin for a purpose other than that indication is off-label — general visceral-fat reduction in people without HIV, anti-ageing use, cognitive enhancement and non-HIV fatty liver disease all fall outside it. It also means research-grade material sold under the drug name is not the approved product and carries none of its purity or potency oversight.

The trial evidence ^[17][19][21] was generated in HIV-positive adults on antiretroviral therapy, and that population is part of what the result means.

What does tesamorelin do?

It reduces visceral adipose tissue — the deep fat packed around the internal organs — and hepatic fat, while increasing lean body mass.

A 2026 meta-analysis of five randomised controlled trials in HIV-associated lipodystrophy found a mean visceral adipose tissue reduction of -27.71 cm² (95% CI -38.37 to -17.06; P<0.001), a trunk fat reduction of -1.18 kg, a hepatic fat fraction reduction of -4.28%, and a lean body mass increase of +1.42 kg, all at P<0.001 and without serious adverse events ^[17].

That lean-mass result is the sharpest contrast on this desk: every incretin compound here loses lean mass alongside fat, and this one adds it.

The effect is contingent on continued administration. In the 52-week programme, visceral fat reduction was sustained at -18% but reaccumulated on discontinuation ^[21].

How does tesamorelin work?

It binds the growth hormone-releasing hormone receptor on anterior-pituitary somatotroph cells, activating the Gs/adenylyl-cyclase/cAMP/PKA cascade and stimulating synthesis and pulsatile secretion of the body's own growth hormone.

Pulsatile matters. Growth hormone is normally released in bursts rather than continuously, and because tesamorelin amplifies an existing rhythm rather than supplying exogenous hormone at a flat concentration, its metabolic profile differs from recombinant growth hormone — most consequentially with respect to insulin sensitivity.

The released growth hormone drives hepatic production of IGF-1, and the two together promote lipolysis preferentially in visceral rather than subcutaneous fat. In 13 healthy men receiving 2 mg daily for two weeks, mean overnight growth hormone rose by 0.5 µg/L (P=0.004) and IGF-1 by 181 µg/L (P<0.0001), while neither fasting glucose (P=0.93) nor insulin-stimulated glucose uptake (P=0.61) was significantly affected ^[20].

Will tesamorelin help me lose belly fat?

The honest answer separates two different questions that the phrase "belly fat" runs together, and neither of them can be answered for an individual by a website.

What the trials measured. Tesamorelin reduces visceral adipose tissue — the deep fat around the organs, measured by imaging — not subcutaneous fat and not weight on a scale. The pooled randomised evidence reports a mean visceral reduction of -27.71 cm² ^[17], and a six-month randomised trial in 50 adults reported a treatment effect of -42 cm² (P=0.005) ^[19].

In whom. Those trials were conducted in HIV-positive adults on antiretroviral therapy, and the approval is limited to HIV-associated lipodystrophy ^[18]. Extending the result to people without HIV is mechanistically plausible but is not established by large randomised trials, and it is off-label.

Two further facts belong in the same answer: the effect reverses within weeks of stopping ^[21], and this is a prescription decision requiring a clinician, not a search result.