Semaglutide

Status Approved in the US for multiple indicationsBest evidence E1Sources checked 2026-09-17

Semaglutide is approved in the United States across six product configurations, from 2 mg weekly by injection up to 7.2 mg weekly on Wegovy HD, approved 19 March 2026, and up to 25 mg daily as a tablet. SELECT cut major adverse cardiovascular events by 20 percent, but its hierarchical testing failed at cardiovascular death,…

Identity

Sequence: A 31 amino acid GLP-1(7-37) analogue: Aib at position 8, Arg at position 34, and Lys26 acylated with a C18 fatty diacid through a gamma-glutamic acid residue and two 8-amino-3,6-dioxaoctanoic acid units
Formula: C187H291N45O59
Molar mass: 4113.58 g/mol
CAS: 910463-68-2

What it is

Semaglutide is a synthetic 31 amino acid GLP-1 analogue, acylated so that it binds circulating albumin. The half-life is about 165 hours, roughly one week, so steady state takes four to five weeks and each escalation step about a month.

What is approved, and at what dose

The other incretin entries point here. This is a record of what the FDA had approved on 17 September 2026, not an instruction.

Ozempic injection, weekly. 0.25 mg for 4 weeks, then 0.5, 1 and 2 mg, at least 4 weeks per step. Maximum recommended dosage 2 mg weekly.
Ozempic pill, oral daily. 1.5 mg for 30 days, 4 mg for 30 days, then 4 or 9 mg.
Rybelsus, oral daily, outside the US only. 3 mg, then 7 mg, then 7 or 14 mg.
Wegovy injection, weekly. 0.25, 0.5, 1 and 1.7 mg at 4 weeks each, then 2.4 mg, or 1.7 mg.
Wegovy HD, weekly. 7.2 mg, after at least 4 weeks tolerating 2.4 mg.
Wegovy tablets, oral daily. 1.5, 4 and 9 mg at 30 days each, then 25 mg.

Ozempic gained a chronic kidney disease indication on 28 January 2025, on FLOW. Wegovy took accelerated approval for noncirrhotic MASH with F2 to F3 fibrosis on 15 August 2025, conditional on ESSENCE Part 2. Oral semaglutide gained a cardiovascular indication on 17 October 2025, on SOUL. Wegovy tablets at 25 mg followed on 22 December 2025, and the reformulated tablet launched as the Ozempic pill on 4 May 2026, replacing Rybelsus in the US.

Wegovy HD was approved on 19 March 2026 under the FDA Commissioner National Priority Voucher pilot, the first dose above 2.4 mg weekly approved for weight management. In STEP UP, 1,407 adults over 72 weeks, 7.2 mg gave 18.7 percent mean weight change against 15.6 at 2.4 mg and 3.9 on placebo, treatment policy estimand, and dysaesthesia, meaning altered skin sensation, in 22.9 percent against 6.0 and 0.5.

Every product carries the same boxed warning for thyroid C-cell tumours, with the label stating that the human relevance of that rodent finding has not been determined. Personal or family history of medullary thyroid carcinoma or MEN 2 is an absolute contraindication, and pulmonary aspiration under anaesthesia is in Warnings and Precautions.

SELECT, and the hierarchy that failed

SELECT randomised 17,604 adults with cardiovascular disease and BMI 27 or higher, without diabetes, to 2.4 mg weekly or placebo. MACE fell from 8.0 to 6.5 percent, hazard ratio 0.80, 0.72 to 0.90.

Confirmatory secondary endpoints were then tested in a prespecified fixed sequence, and the first, cardiovascular death, missed at p equals 0.07. Under that procedure every endpoint below it is nominal rather than confirmatory, including all-cause mortality at 0.81. SELECT established a MACE reduction. It did not formally establish that semaglutide reduces cardiovascular death or death from any cause, and sources stating those as findings overstate it. Discontinuation for adverse events ran 16.6 percent against 8.2 on placebo, one in six, in a trial with funded drug and structured follow-up.

The prespecified adiposity analysis in the Lancet in 2025 is the most consequential secondary finding. The MACE reduction held across every baseline weight and waist category, no relationship appeared between weight lost by week 20 and later MACE risk on semaglutide, and only about 33 percent of the benefit was mediated through waist circumference. That is the anchor for the rest of this encyclopedia. A compound that produces more weight loss than semaglutide has not thereby been shown to do more for the heart.

FLOW, the stronger trial

FLOW randomised 3,533 adults with type 2 diabetes and chronic kidney disease to semaglutide 1.0 mg weekly, not 2.4 mg, or placebo, and stopped early at a prespecified interim analysis. The primary kidney composite gave hazard ratio 0.76, 0.66 to 0.88.

Its hierarchy held. Cardiovascular death 0.71, MACE 0.82 and death from any cause 0.80, the last at p equals 0.01, are confirmatory findings, not nominal ones. The mortality claim people attach to SELECT lives here instead, at 1 mg weekly, which is why the chronic kidney disease instruction on the Ozempic label stops at 1 mg.

What it did not do

EVOKE and EVOKE-plus randomised 3,808 adults with mild cognitive impairment or mild dementia due to Alzheimer disease to oral semaglutide 14 mg or placebo for 104 weeks. It did not separate from placebo on CDR-SB, and the extension was discontinued. That ends the neuroprotection framing.

STRIDE improved walking distance in peripheral artery disease and the EU committee recommended an Ozempic label update on 23 June 2025. As of 17 September 2026 there was no US indication, unchecked past that date.

Lean mass, regain and persistence

The STEP 1 DXA substudy scanned 140 participants at week 68. Total fat mass fell 19.3 percent, lean body mass 9.7 percent and visceral fat 27.4 percent. The much repeated 40 percent lean tissue figure is a derivation from those percentages, not a number the substudy reported.

The 2026 Annals of Internal Medicine review of 35 randomised trials found a median 28.3 percent of weight loss attributable to muscle-based indices. No study in it reported an objective physical function outcome, not one. And 38 percent of lifestyle comparator groups also exceeded the benchmark, which is what losing weight does however it is done.

Two regain figures circulate, both true of different situations. In the STEP 1 off-treatment extension, 327 participants who had lost a mean 17.3 percent regained 11.6 percentage points by week 120, about two thirds of the loss. In a 2026 Cleveland Clinic cohort of 7,938 people who stopped in practice, the obesity group regained a mean of 0.5 percent at one year, because many restarted or switched, which a randomised withdrawal design prevents.

The buried number sits under both. A Prime Therapeutics analysis of 5,780 insured members without diabetes found three-year persistence of 8.1 percent overall and 14.3 percent for weekly semaglutide. In the community, the modal outcome is stopping.

NAION, where regulators split

The EMA safety committee concluded in June 2025 that non-arteritic anterior ischaemic optic neuropathy is an adverse effect of semaglutide, very rare, up to 1 in 10,000. The MHRA followed on 5 February 2026, at about one extra case per 10,000 treated per year. On the US labels NAION is not in Warnings and Precautions, and whether the FDA has added it since 17 September 2026 has not been verified. Pages saying the FDA warns about vision loss were wrong as of that check.

The evidence conflicts. A 2026 meta-analysis in Graefes Archive, eight cohorts and 14,255,247 participants, gave a pooled hazard ratio of 2.37 at two years. A 2026 Military Medicine cohort of 1,212,775 beneficiaries found the opposite direction in type 2 diabetes, odds ratio 0.36. The Disc-at-Risk Study Group, Ophthalmology 2026, found crowded disc anatomy identical in semaglutide users, other GLP-1 users and non-users, with a cup-to-disc ratio of 0.20 or less carrying 46 times the odds of NAION. The dominant risk factor is a disc the person was born with.

What circulates, and why no numbers appear here

Compounding at scale was lawful only while the shortage listing stood. The FDA determined the semaglutide shortage resolved on 21 February 2025, and enforcement discretion ended for 503A compounders on 22 April 2025 and 503B facilities on 22 May 2025. More than 50 warning letters followed that September, alongside an import alert detaining GLP-1 bulk substance from manufacturers not on the FDA Green List. By 31 May 2026 the agency held 990 adverse event reports for compounded semaglutide.

This site does not reproduce the figures that circulate for semaglutide. The escalation is where the harm sits, and the vials have been shown not to contain what the label says.

Ashraf and colleagues, Journal of Medical Internet Research 2024, test-purchased from illegal online pharmacies. In the delivered vials, measured purity was 7.7 to 14.37 percent against 99 percent claimed, while total semaglutide content ran 28.56 to 38.69 percent above the labelled amount, and endotoxin was in every sample. Both errors at once means no dose is calculable from such a label.

A 2026 EudraVigilance analysis of 234 reports involving suspected counterfeit semaglutide found 89.3 percent serious and a reporting odds ratio of 10.27 for hypoglycaemia. Semaglutide alone does not readily cause hypoglycaemia, because its insulinotropic effect is glucose-dependent. A tenfold excess is most consistent with those products containing insulin or a sulfonylurea instead.

What is not known

Whether the FDA has added NAION to US labelling. On the labels checked for this entry, Ozempic and oral semaglutide revised 10/2025 and Wegovy revised 02/2026, it is not in Warnings and Precautions, while the EMA and MHRA have added it at a very rare frequency. That is the position as of 17 September 2026 and it has not been verified beyond that date.

Whether a US peripheral artery disease indication exists. STRIDE met its walking distance endpoint and the EU committee recommended a label update on 23 June 2025, but the October 2025 US Ozempic label carried no such indication. Also unverified past 17 September 2026.

Whether the MASH histology benefit becomes a clinical outcome. The August 2025 approval is an accelerated one, granted on ESSENCE Part 1 at week 72, and Part 2 runs to week 240 before anyone knows whether liver outcomes follow.

Whether lean tissue loss costs strength or function. The 2026 Annals of Internal Medicine review of 35 trials found that not one of them reported an objective physical function outcome, so the question that actually matters has never been measured in a trial.

Whether the dysaesthesia seen at 7.2 mg persists or resolves. Both STEP UP trials reported it at roughly four times the 2.4 mg rate, neither publication offered a mechanism, and nothing characterises its duration.

Whether semaglutide and SGLT2 inhibitors add together on kidney endpoints. The FLOW subgroup on baseline SGLT2 inhibitor therapy had only 79 events, gave a hazard ratio of 1.07 against 0.73 in non-users, and an interaction p of 0.109. That is an underpowered subgroup, not evidence of no benefit.

Doses used in published research

Semaglutide has approved doses, which is rare on this site. They differ by product and by indication, and every one of them came from a randomised trial. What follows is a record of what a regulator approved, not an instruction.

By injection, weekly. Ozempic escalates 0.25 mg for four weeks, then 0.5, 1 and 2 mg with at least four weeks per step, to a maximum recommended dosage of 2 mg. Wegovy escalates 0.25, 0.5, 1 and 1.7 mg at four weeks each, then 2.4 mg maintenance with 1.7 mg as the stated alternative. Wegovy HD is 7.2 mg weekly, only after at least four weeks tolerating 2.4 mg.

By mouth, daily. The Ozempic pill escalates 1.5 mg, then 4 mg, at 30 days each, then 4 or 9 mg. Rybelsus, now marketed outside the US, escalates 3 mg, then 7 mg, then 7 or 14 mg. Wegovy tablets escalate 1.5, 4 and 9 mg at 30 days each, then 25 mg. All oral products carry the same administration rule, on an empty stomach with no more than 4 ounces of plain water and at least 30 minutes before anything else.

Two doses belong to specific trials rather than to a general ceiling. FLOW used 1.0 mg weekly, and the chronic kidney disease instruction on the Ozempic label follows that trial dose rather than going to 2 mg. STEP UP tested 7.2 mg and found dysaesthesia in 22.9 percent of participants against 6.0 percent at 2.4 mg.

The escalation schedule is not a formality. The half-life is about one week, so each step takes four to five weeks to reach steady state, and compressing the schedule is one of the dosing errors the FDA has linked to hospitalisations in the compounded market.

Compiled from: WEGOVY prescribing information

An approved dose exists for the labelled indication above. No dose has been established as safe or effective for any use outside that label.

Amounts above record what a named source reported administering in a study. They are not a recommendation, not a protocol, and not instructions.

Converting a vial and a syringe into a draw volume is a separate, mechanical question from what amount to use. The reconstitution calculator does that arithmetic for peptide, HCG, and HGH vials.