Semaglutide - Revision history

MDElliottMD: Strip Category:MedCategory marker per interface-claude 2026-05-20 hygiene order: this page is a medicine, narrative, wiki-meta page, or stylesheet rather than a class-overview category, so it should not carry the MedCategory tag. Class memberships and other tags preserved.

2026-05-19T18:00:11Z

Strip Category:MedCategory marker per interface-claude 2026-05-20 hygiene order: this page is a medicine, narrative, wiki-meta page, or stylesheet rather than a class-overview category, so it should not carry the MedCategory tag. Class memberships and other tags preserved.

← Older revision		Revision as of 18:00, 19 May 2026
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	}}		}}

	~~[[Category:MedCategory]]~~
	[[Category:GLP-1 receptor agonists]]		[[Category:GLP-1 receptor agonists]]
	[[Category:Antidiabetic medicines]]		[[Category:Antidiabetic medicines]]
	[[Category:Anti-obesity medicines]]		[[Category:Anti-obesity medicines]]
	[[Category:Novo Nordisk medicines]]		[[Category:Novo Nordisk medicines]]

MDElliottMD: Em-dash sweep: replace em-dash with comma per project rule; PendellsCorner verbatim quotes preserved.

2026-05-19T03:16:11Z

Em-dash sweep: replace em-dash with comma per project rule; PendellsCorner verbatim quotes preserved.

MDElliottMD: Sweep: "indications" -> "problems" sitewide terminology update (preserves MedTemplate param name)

2026-05-19T01:37:45Z

Sweep: "indications" -> "problems" sitewide terminology update (preserves MedTemplate param name)

← Older revision		Revision as of 01:37, 19 May 2026
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	Importantly: semaglutide is '''not a contraceptive''', and the medicine may '''restore ovulation''' in patients with [[PCOS]] or [[obesity]]-associated anovulation.{{Citation needed}} Patients of childbearing potential should be counseled about contraception ''before'' starting.		Importantly: semaglutide is '''not a contraceptive''', and the medicine may '''restore ovulation''' in patients with [[PCOS]] or [[obesity]]-associated anovulation.{{Citation needed}} Patients of childbearing potential should be counseled about contraception ''before'' starting.

	\| monitoring = * Baseline: HbA1c, weight, BP, renal function, lipid panel, [[ALT]]/AST (especially for MASH ~~indication~~)		\| monitoring = * Baseline: HbA1c, weight, BP, renal function, lipid panel, [[ALT]]/AST (especially for MASH problem)
	* Personal or family history of MTC or [[MEN2]] — '''contraindicated''', do not start<ref name="ozempic-label"/>		* Personal or family history of MTC or [[MEN2]] — '''contraindicated''', do not start<ref name="ozempic-label"/>
	* Every 3 months for first year: HbA1c, weight, GI tolerability, signs of [[pancreatitis]] or [[gallbladder disease]]		* Every 3 months for first year: HbA1c, weight, GI tolerability, signs of [[pancreatitis]] or [[gallbladder disease]]

MDElliottMD: Migrate tags to (Phase 2 of indications-to-problems rebuild)

2026-05-17T00:11:52Z

Migrate <indication> tags to <problem> (Phase 2 of indications-to-problems rebuild)

← Older revision		Revision as of 00:11, 17 May 2026
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	* 24% relative risk reduction in kidney + CV composite in T2DM + CKD (FLOW)<ref name="flow">Perkovic V et al. (2024). Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes (FLOW). ''NEJM'' 391:109. doi:10.1056/NEJMoa2403347</ref>		* 24% relative risk reduction in kidney + CV composite in T2DM + CKD (FLOW)<ref name="flow">Perkovic V et al. (2024). Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes (FLOW). ''NEJM'' 391:109. doi:10.1056/NEJMoa2403347</ref>

	\| indications = <~~indication~~ ref="diabetes-type-2" author="MDElliottMD"/>		\| indications = <problem ref="diabetes-type-2" author="MDElliottMD"/>
	<~~indication~~ ref="obesity" author="MDElliottMD"/>		<problem ref="obesity" author="MDElliottMD"/>
	<~~indication~~ ref="cv-risk-obesity" author="MDElliottMD"/>		<problem ref="cv-risk-obesity" author="MDElliottMD"/>
	<~~indication~~ ref="mash-fibrosis" author="MDElliottMD"/>		<problem ref="mash-fibrosis" author="MDElliottMD"/>
	<~~indication~~ ref="ckd-t2dm" author="MDElliottMD"/>		<problem ref="ckd-t2dm" author="MDElliottMD"/>

	\| dosing = <titration slug="ozempic-standard" author="MDElliottMD" title="Ozempic — standard T2DM titration">		\| dosing = <titration slug="ozempic-standard" author="MDElliottMD" title="Ozempic — standard T2DM titration">

MDElliottMD: Fix Cargo VARCHAR(300) overflow: blank structure, shorten mechanism, move chemistry/mechanism prose to PK/PD

2026-05-16T23:33:07Z

Fix Cargo VARCHAR(300) overflow: blank structure, shorten mechanism, move chemistry/mechanism prose to PK/PD

← Older revision		Revision as of 23:33, 16 May 2026
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	\| generic = Semaglutide		\| generic = Semaglutide
	\| brand = Ozempic (T2DM SC), Wegovy (obesity SC), Rybelsus (oral T2DM)		\| brand = Ozempic (T2DM SC), Wegovy (obesity SC), Rybelsus (oral T2DM)
	\| structure = 31-amino-acid acylated peptide analog of human [[GLP-1]] (7–37), with Aib substitution at position 8 (blocks DPP-4 cleavage) and a C18 fatty diacid linked via γGlu-2×OEG spacer at Lys26 (drives albumin binding → ~165 h half-life)<ref name="lau2015">Lau J, Bloch P, Schäffer L et al. (2015). Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutide. ''J Med Chem'' 58(18):7370–80. doi:10.1021/acs.jmedchem.5b00726</ref>		\| structure =

	\| classes = [[GLP-1 receptor agonist]] · [[Antidiabetic medicines\|Antidiabetic]] · [[Anti-obesity medicines\|Anti-obesity]] · [[Cardiovascular risk reduction]] agent		\| classes = [[GLP-1 receptor agonist]] · [[Antidiabetic medicines\|Antidiabetic]] · [[Anti-obesity medicines\|Anti-obesity]] · [[Cardiovascular risk reduction]] agent
	\| mechanism = ~~Selective long~~-acting agonist of the [[GLP-1 receptor]] ~~(class B GPCR)~~. Produces glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, hypothalamic appetite suppression, and direct cardiovascular and renal protective effects.<ref name="drucker2022">Drucker DJ (2022). GLP-1 physiology informs the pharmacotherapy of obesity. ''Mol Metab'' 57:101351. doi:10.1016/j.molmet.2021.101351</ref>		\| mechanism = Long-acting agonist of the [[GLP-1 receptor]].

	\| uses = [[Type 2 diabetes mellitus]] · [[Obesity]] · [[Cardiovascular risk reduction]] in obesity without diabetes · [[MASH]] with stage 2–3 fibrosis · [[Chronic kidney disease]] in T2DM		\| uses = [[Type 2 diabetes mellitus]] · [[Obesity]] · [[Cardiovascular risk reduction]] in obesity without diabetes · [[MASH]] with stage 2–3 fibrosis · [[Chronic kidney disease]] in T2DM
	\| starting_dose = Ozempic: 0.25 mg SC weekly × 4 wk<ref name="ozempic-label">US FDA. ''Ozempic (semaglutide) prescribing information.'' Novo Nordisk. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/209637s019lbl.pdf</ref> · Wegovy: 0.25 mg SC weekly × 4 wk<ref name="wegovy-label">US FDA. ''Wegovy (semaglutide) prescribing information.'' Novo Nordisk. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215256s000lbl.pdf</ref> · Rybelsus: 3 mg PO daily × 30 d<ref name="rybelsus-label">US FDA. ''Rybelsus (semaglutide) prescribing information.'' Novo Nordisk. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/213051s000lbl.pdf</ref>		\| starting_dose = Ozempic: 0.25 mg SC weekly × 4 wk<ref name="ozempic-label">US FDA. ''Ozempic (semaglutide) prescribing information.'' Novo Nordisk. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/209637s019lbl.pdf</ref> · Wegovy: 0.25 mg SC weekly × 4 wk<ref name="wegovy-label">US FDA. ''Wegovy (semaglutide) prescribing information.'' Novo Nordisk. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215256s000lbl.pdf</ref> · Rybelsus: 3 mg PO daily × 30 d<ref name="rybelsus-label">US FDA. ''Rybelsus (semaglutide) prescribing information.'' Novo Nordisk. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/213051s000lbl.pdf</ref>
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	Semaglutide is the second weekly GLP-1 RA from Novo Nordisk's incretin program (after [[liraglutide]])<ref name="lau2015"/> and the molecule that, more than any other, made obesity treatment a mainstream rather than a specialty intervention.{{Citation needed}}		Semaglutide is the second weekly GLP-1 RA from Novo Nordisk's incretin program (after [[liraglutide]])<ref name="lau2015"/> and the molecule that, more than any other, made obesity treatment a mainstream rather than a specialty intervention.{{Citation needed}}

	\| pharmacokinetics = Acylation with a C18 fatty diacid drives non-covalent binding to serum albumin, slowing renal clearance and DPP-4 access. The Aib8 substitution renders the peptide DPP-4-resistant. Resulting terminal half-life ~165 h means once-weekly subcutaneous dosing produces near-steady-state plasma levels.<ref name="lau2015"/>		\| pharmacokinetics = '''Chemistry'''. 31-amino-acid acylated peptide analog of human [[GLP-1]] (7–37), with Aib substitution at position 8 (blocks DPP-4 cleavage) and a C18 fatty diacid linked via γGlu-2×OEG spacer at Lys26 (drives albumin binding → ~165 h half-life)<ref name="lau2015">Lau J, Bloch P, Schäffer L et al. (2015). Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutide. ''J Med Chem'' 58(18):7370–80. doi:10.1021/acs.jmedchem.5b00726</ref>

			Acylation with a C18 fatty diacid drives non-covalent binding to serum albumin, slowing renal clearance and DPP-4 access. The Aib8 substitution renders the peptide DPP-4-resistant. Resulting terminal half-life ~165 h means once-weekly subcutaneous dosing produces near-steady-state plasma levels.<ref name="lau2015"/>

	Oral semaglutide (Rybelsus) is co-formulated with '''SNAC''' (sodium N-[8-(2-hydroxybenzoyl)amino]caprylate), a permeation enhancer that transiently raises gastric pH and protects the peptide locally — yielding ~0.4–1% bioavailability, which is sufficient at 14 mg daily to match Ozempic 0.5 mg weekly for glycemic effect (but not for weight loss).<ref name="rybelsus-label"/><ref name="buckley2018">Buckley ST, Bækdal TA, Vegge A et al. (2018). Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist. ''Sci Transl Med'' 10(467):eaar7047. doi:10.1126/scitranslmed.aar7047</ref> Strict fasting administration is mandatory; any concurrent food or beverage destroys absorption.<ref name="rybelsus-label"/>		Oral semaglutide (Rybelsus) is co-formulated with '''SNAC''' (sodium N-[8-(2-hydroxybenzoyl)amino]caprylate), a permeation enhancer that transiently raises gastric pH and protects the peptide locally — yielding ~0.4–1% bioavailability, which is sufficient at 14 mg daily to match Ozempic 0.5 mg weekly for glycemic effect (but not for weight loss).<ref name="rybelsus-label"/><ref name="buckley2018">Buckley ST, Bækdal TA, Vegge A et al. (2018). Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist. ''Sci Transl Med'' 10(467):eaar7047. doi:10.1126/scitranslmed.aar7047</ref> Strict fasting administration is mandatory; any concurrent food or beverage destroys absorption.<ref name="rybelsus-label"/>
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	Predominantly catabolic clearance via proteolysis; renal and hepatic impairment do not require dose adjustment.<ref name="ozempic-label"/> No CYP-mediated metabolism, so the interaction profile is dominated by ''gastric emptying'' effects on other oral medicines, not pharmacokinetic competition.<ref name="ozempic-label"/>		Predominantly catabolic clearance via proteolysis; renal and hepatic impairment do not require dose adjustment.<ref name="ozempic-label"/> No CYP-mediated metabolism, so the interaction profile is dominated by ''gastric emptying'' effects on other oral medicines, not pharmacokinetic competition.<ref name="ozempic-label"/>

	\| pharmacodynamics = At maintenance doses semaglutide produces:		\| pharmacodynamics = '''Receptor pharmacology'''. Selective long-acting agonist of the [[GLP-1 receptor]] (class B GPCR). Produces glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, hypothalamic appetite suppression, and direct cardiovascular and renal protective effects.<ref name="drucker2022">Drucker DJ (2022). GLP-1 physiology informs the pharmacotherapy of obesity. ''Mol Metab'' 57:101351. doi:10.1016/j.molmet.2021.101351</ref>

			At maintenance doses semaglutide produces:
	* HbA1c reduction of ~1.5–2.0 percentage points (Ozempic 1 mg)<ref name="sustain6">Marso SP et al. (2016). Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6). ''NEJM'' 375:1834–44. doi:10.1056/NEJMoa1607141</ref>		* HbA1c reduction of ~1.5–2.0 percentage points (Ozempic 1 mg)<ref name="sustain6">Marso SP et al. (2016). Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6). ''NEJM'' 375:1834–44. doi:10.1056/NEJMoa1607141</ref>
	* Weight loss of ~6 kg (Ozempic 1 mg, T2DM)<ref name="sustain6"/> to ~14.9% body weight (Wegovy 2.4 mg, obesity without T2DM, STEP-1)<ref name="step1"/>		* Weight loss of ~6 kg (Ozempic 1 mg, T2DM)<ref name="sustain6"/> to ~14.9% body weight (Wegovy 2.4 mg, obesity without T2DM, STEP-1)<ref name="step1"/>

MDElliottMD: Backfill inline citations per new sitewide citation rule

2026-05-16T22:58:15Z

Backfill inline <ref> citations per new sitewide citation rule

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MDElliottMD: Create Semaglutide page (initial draft, MedTemplate)

2026-05-16T22:35:18Z

Create Semaglutide page (initial draft, MedTemplate)

New page

{{MedTemplate
| generic = Semaglutide
| brand = Ozempic (T2DM SC), Wegovy (obesity SC), Rybelsus (oral T2DM)
| structure = 31-amino-acid acylated peptide analog of human [[GLP-1]] (7–37), with Aib substitution at position 8 (blocks DPP-4 cleavage) and a C18 fatty diacid linked via γGlu-2×OEG spacer at Lys26 (drives albumin binding → ~165 h half-life)
| classes = [[GLP-1 receptor agonist]] · [[Antidiabetic medicines|Antidiabetic]] · [[Anti-obesity medicines|Anti-obesity]] · [[Cardiovascular risk reduction]] agent
| mechanism = Selective long-acting agonist of the [[GLP-1 receptor]] (class B GPCR). Produces glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, hypothalamic appetite suppression, and direct cardiovascular and renal protective effects.
| uses = [[Type 2 diabetes mellitus]] · [[Obesity]] · [[Cardiovascular risk reduction]] in obesity without diabetes · [[MASH]] with stage 2–3 fibrosis · [[Chronic kidney disease]] in T2DM
| starting_dose = Ozempic: 0.25 mg SC weekly × 4 wk · Wegovy: 0.25 mg SC weekly × 4 wk · Rybelsus: 3 mg PO daily × 30 d
| preparations = Pre-filled multi-dose pen (0.25 / 0.5 / 1 / 2 mg, Ozempic; 0.25 / 0.5 / 1 / 1.7 / 2.4 mg, Wegovy) · Oral tablet 3 / 7 / 14 mg co-formulated with SNAC absorption enhancer (Rybelsus)
| fda_max = 2 mg/wk SC (Ozempic) · 2.4 mg/wk SC (Wegovy) · 14 mg PO daily (Rybelsus)
| routes = Subcutaneous (abdomen, thigh, upper arm) · Oral (Rybelsus only, on empty stomach with ≤120 mL water, ≥30 min before any food/drink/other oral medicine)
| onset = Glycemic effect within days; full weight effect over months
| duration = ~7 days (weekly SC dosing) · ~24 h (oral)
| halflife = ~165 hours (~1 week) — among the longest of any GLP-1 RA
| bioavailability = SC ~89% · Oral ~0.4–1% (SNAC-enhanced)
| pregnancy = Avoid. Discontinue ≥2 months before planned pregnancy due to long half-life. Animal data show embryofetal harm. Not contraceptive — but rapid weight loss + improved ovulation may unmask fertility in [[PCOS]].
| legal = Rx-only · Schedule: none (not a controlled substance)
| intro = Semaglutide is a long-acting [[GLP-1 receptor agonist]] developed by [[Novo Nordisk]], marketed as '''[[Ozempic]]''' (weekly subcutaneous, for [[type 2 diabetes mellitus]]), '''[[Wegovy]]''' (weekly subcutaneous, for [[obesity]], [[cardiovascular risk reduction]] in obesity without diabetes, and [[MASH]] with fibrosis), and '''[[Rybelsus]]''' (daily oral tablet, for T2DM). It is, by revenue, the highest-grossing medicine on the planet as of 2024.

Semaglutide is the second weekly GLP-1 RA from Novo Nordisk's incretin program (after [[liraglutide]]) and the molecule that, more than any other, made obesity treatment a mainstream rather than a specialty intervention.

| pharmacokinetics = Acylation with a C18 fatty diacid drives non-covalent binding to serum albumin, slowing renal clearance and DPP-4 access. The Aib8 substitution renders the peptide DPP-4-resistant. Resulting terminal half-life ~165 h means once-weekly subcutaneous dosing produces near-steady-state plasma levels.

Oral semaglutide (Rybelsus) is co-formulated with '''SNAC''' (sodium N-[8-(2-hydroxybenzoyl)amino]caprylate), a permeation enhancer that transiently raises gastric pH and protects the peptide locally — yielding ~0.4–1% bioavailability, which is enough at 14 mg daily to match Ozempic 0.5 mg weekly for glycemic effect (but not for weight loss). Strict fasting administration is mandatory; any concurrent food or beverage destroys absorption.

Predominantly catabolic clearance via proteolysis; renal and hepatic impairment do not require dose adjustment. No CYP-mediated metabolism, so the interaction profile is dominated by ''gastric emptying'' effects on other oral medicines, not pharmacokinetic competition.

| pharmacodynamics = At maintenance doses semaglutide produces:
* HbA1c reduction of ~1.5–2.0 percentage points (Ozempic 1 mg)
* Weight loss of ~6 kg (Ozempic 1 mg, T2DM) to ~15% body weight (Wegovy 2.4 mg, obesity without T2DM, STEP-1)
* Systolic BP reduction of ~5 mmHg
* Modest LDL-C reduction, larger triglyceride reduction
* 20% relative risk reduction in MACE in obesity without T2DM (SELECT)
* 24% relative risk reduction in kidney + CV composite in T2DM + CKD (FLOW)

| indications = <indication ref="diabetes-type-2" author="MDElliottMD"/>
<indication ref="obesity" author="MDElliottMD"/>
<indication ref="cv-risk-obesity" author="MDElliottMD"/>
<indication ref="mash-fibrosis" author="MDElliottMD"/>
<indication ref="ckd-t2dm" author="MDElliottMD"/>

| dosing = <titration slug="ozempic-standard" author="MDElliottMD" title="Ozempic — standard T2DM titration">
0.25 mg SC weekly × 4 weeks (non-therapeutic; tolerance ramp only)
→ 0.5 mg SC weekly × ≥4 weeks
→ 1 mg SC weekly × ≥4 weeks if further glycemic control needed
→ 2 mg SC weekly (max) if needed

Slower titration is reasonable in any patient with significant GI symptoms — holding at a tolerated dose for 8–12 weeks before advancing is standard practice.
</titration>

<titration slug="wegovy-standard" author="MDElliottMD" title="Wegovy — standard obesity titration">
0.25 mg SC weekly × 4 weeks
→ 0.5 mg × 4 weeks
→ 1 mg × 4 weeks
→ 1.7 mg × 4 weeks
→ 2.4 mg weekly (maintenance)

If a dose escalation is not tolerated, hold at the prior dose for an extra 4 weeks before advancing. Discontinue if patient cannot tolerate 1.7 mg after extended titration.
</titration>

<titration slug="rybelsus-standard" author="MDElliottMD" title="Rybelsus — standard oral T2DM titration">
3 mg PO daily × 30 days (non-therapeutic ramp)
→ 7 mg PO daily × ≥30 days
→ 14 mg PO daily (max)

'''Critical patient instruction''': swallow whole, with no more than 120 mL (4 oz) of plain water, on an empty stomach, ≥30 minutes before the first food, drink, or any other oral medicine of the day.
</titration>

| effects = Subjective effects vary considerably with dose and titration speed but reliably include:
* '''Early satiety''' — meals feel "complete" at a fraction of prior intake
* '''Food noise quieting''' — the most commonly volunteered subjective change. Patients report that intrusive food-related thoughts simply stop.
* '''Reduced alcohol craving''' — corroborated by observational and small RCT data; mechanism likely shared with food reward circuitry
* '''Nausea''' — dose-dependent, worst in first 1–2 weeks of any new dose level
* '''Constipation or diarrhea''' (variable, can alternate)
* '''Sulfurous eructation''' (a small but very real subgroup)
* '''Reduced taste preference for fatty / sweet foods''' in many users

| interactions = <pharmaInteractions/>

| pregnancy_details = Category formerly X-equivalent; current FDA labeling: avoid in pregnancy. Animal embryofetal toxicity is well-documented. Because the half-life is ~1 week, current guidance is to '''discontinue at least 2 months before any planned conception'''.

Postpartum: not recommended during breastfeeding pending more data; small molecule transfer to milk is unlikely given peptide structure but not formally characterized.

Importantly: semaglutide is '''not a contraceptive''', and the medicine may '''restore ovulation''' in patients with [[PCOS]] or [[obesity]]-associated anovulation. Patients of childbearing potential should be counseled about contraception ''before'' starting.

| monitoring = * Baseline: HbA1c, weight, BP, renal function, lipid panel, [[ALT]]/AST (especially for MASH indication)
* Personal or family history of MTC or [[MEN2]] — '''contraindicated''', do not start
* Every 3 months for first year: HbA1c, weight, GI tolerability, signs of [[pancreatitis]] or [[gallbladder disease]]
* Annual: renal function, lipids
* '''Pre-procedure''': hold weekly dose ≥7 days before any planned anesthesia (per [[ASA 2024 guidance]]) due to delayed gastric emptying / aspiration risk

| counseling = * '''Slow titration is non-negotiable''' for tolerability. Patients who insist on faster ramps usually quit from GI side effects.
* Inject SC in abdomen, thigh, or upper arm; rotate sites. Pen is single-patient, multi-dose.
* GI side effects almost always peak in first 2–4 weeks of any new dose level, then attenuate.
* Eat smaller portions earlier in the day. Plate sizes will feel comically large after a few weeks — that is the medicine working, not a problem to fix.
* Hydrate aggressively (volume depletion → AKI is a real risk).
* Resistance training during weight loss protects lean mass and is strongly encouraged.
* If a weekly dose is missed: take within 5 days; if >5 days, skip and resume on the next regular day.
* Avoid alcohol during titration weeks (compounds nausea).
* '''Pregnancy planning''': stop ≥2 months before trying to conceive.
* '''Surgery''': tell every anesthesiologist and surgeon you are on a weekly GLP-1 RA. Hold dose 7 days pre-op.

| anecdotes = <vote slug="food-noise"/>
<vote slug="early-satiety"/>
<vote slug="alcohol-craving"/>
<vote slug="nausea-titration"/>

| seealso = [[GLP-1 receptor agonist]] · [[Tirzepatide]] · [[Liraglutide]] · [[Dulaglutide]] · [[Exenatide]] · [[Type 2 diabetes mellitus]] · [[Obesity]] · [[MASH]]

| references = <ref name="step1">Wilding JPH et al. (2021). Once-weekly semaglutide in adults with overweight or obesity (STEP-1). ''NEJM'' 384:989.</ref>
<ref name="sustain6">Marso SP et al. (2016). Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6). ''NEJM'' 375:1834–44.</ref>
<ref name="select">Lincoff AM et al. (2023). Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). ''NEJM'' 389:2221–32.</ref>
<ref name="flow">Perkovic V et al. (2024). Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes (FLOW). ''NEJM'' 391:109.</ref>
<ref name="essence">Newsome PN et al. (2025). Semaglutide in MASH (ESSENCE). FDA approval basis.</ref>
<ref name="pioneer6">Husain M et al. (2019). Oral semaglutide and cardiovascular outcomes in patients with T2DM (PIONEER-6). ''NEJM'' 381:841.</ref>
<ref name="stephfpef">Kosiborod MN et al. (2023). Semaglutide in patients with HFpEF and obesity (STEP-HFpEF). ''NEJM'' 389:1069.</ref>
<ref name="drucker2022">Drucker DJ (2022). GLP-1 physiology informs the pharmacotherapy of obesity. ''Mol Metab'' 57:101351.</ref>
<ref name="kindel2024">Kindel TL et al. (2024). Perioperative GLP-1 RA safety guidance. ''Surg Obes Relat Dis'' 20(12):1183.</ref>
}}

[[Category:MedCategory]]
[[Category:GLP-1 receptor agonists]]
[[Category:Antidiabetic medicines]]
[[Category:Anti-obesity medicines]]
[[Category:Novo Nordisk medicines]]

← Older revision		Revision as of 03:16, 19 May 2026
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	\| onset = Glycemic effect within days;{{Citation needed}} full weight effect over months<ref name="step1">Wilding JPH et al. (2021). Once-weekly semaglutide in adults with overweight or obesity (STEP-1). ''NEJM'' 384:989. doi:10.1056/NEJMoa2032183</ref>		\| onset = Glycemic effect within days;{{Citation needed}} full weight effect over months<ref name="step1">Wilding JPH et al. (2021). Once-weekly semaglutide in adults with overweight or obesity (STEP-1). ''NEJM'' 384:989. doi:10.1056/NEJMoa2032183</ref>
	\| duration = ~7 days (weekly SC dosing)<ref name="ozempic-label"/> · ~24 h (oral)<ref name="rybelsus-label"/>		\| duration = ~7 days (weekly SC dosing)<ref name="ozempic-label"/> · ~24 h (oral)<ref name="rybelsus-label"/>
	\| halflife = ~165 hours (~1 week) — among the longest of any GLP-1 RA<ref name="lau2015"/>		\| halflife = ~165 hours (~1 week), among the longest of any GLP-1 RA<ref name="lau2015"/>
	\| bioavailability = SC ~89%{{Citation needed}} · Oral ~0.4–1% (SNAC-enhanced)<ref name="rybelsus-label"/>		\| bioavailability = SC ~89%{{Citation needed}} · Oral ~0.4–1% (SNAC-enhanced)<ref name="rybelsus-label"/>
	\| pregnancy = Avoid. Discontinue ≥2 months before planned pregnancy due to long half-life. Animal data show embryofetal harm.<ref name="ozempic-label"/> Not contraceptive — but rapid weight loss + improved ovulation may unmask fertility in [[PCOS]].{{Citation needed}}		\| pregnancy = Avoid. Discontinue ≥2 months before planned pregnancy due to long half-life. Animal data show embryofetal harm.<ref name="ozempic-label"/> Not contraceptive, but rapid weight loss + improved ovulation may unmask fertility in [[PCOS]].{{Citation needed}}
	\| legal = Rx-only;<ref name="ozempic-label"/> not a controlled substance		\| legal = Rx-only;<ref name="ozempic-label"/> not a controlled substance
	\| intro = Semaglutide is a long-acting [[GLP-1 receptor agonist]] developed by [[Novo Nordisk]], marketed as '''[[Ozempic]]''' (weekly subcutaneous, for [[type 2 diabetes mellitus]]),<ref name="ozempic-label"/> '''[[Wegovy]]''' (weekly subcutaneous, for [[obesity]], [[cardiovascular risk reduction]] in obesity without diabetes, and [[MASH]] with fibrosis),<ref name="wegovy-label"/><ref name="select">Lincoff AM et al. (2023). Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). ''NEJM'' 389:2221–32. doi:10.1056/NEJMoa2307563</ref><ref name="essence">Newsome PN et al. (2025). Semaglutide in MASH (ESSENCE). FDA approval basis. {{Citation needed}}</ref> and '''[[Rybelsus]]''' (daily oral tablet, for T2DM).<ref name="rybelsus-label"/> It is, by revenue, among the highest-grossing medicines on the planet as of 2024.{{Citation needed}}		\| intro = Semaglutide is a long-acting [[GLP-1 receptor agonist]] developed by [[Novo Nordisk]], marketed as '''[[Ozempic]]''' (weekly subcutaneous, for [[type 2 diabetes mellitus]]),<ref name="ozempic-label"/> '''[[Wegovy]]''' (weekly subcutaneous, for [[obesity]], [[cardiovascular risk reduction]] in obesity without diabetes, and [[MASH]] with fibrosis),<ref name="wegovy-label"/><ref name="select">Lincoff AM et al. (2023). Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). ''NEJM'' 389:2221–32. doi:10.1056/NEJMoa2307563</ref><ref name="essence">Newsome PN et al. (2025). Semaglutide in MASH (ESSENCE). FDA approval basis. {{Citation needed}}</ref> and '''[[Rybelsus]]''' (daily oral tablet, for T2DM).<ref name="rybelsus-label"/> It is, by revenue, among the highest-grossing medicines on the planet as of 2024.{{Citation needed}}
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	Acylation with a C18 fatty diacid drives non-covalent binding to serum albumin, slowing renal clearance and DPP-4 access. The Aib8 substitution renders the peptide DPP-4-resistant. Resulting terminal half-life ~165 h means once-weekly subcutaneous dosing produces near-steady-state plasma levels.<ref name="lau2015"/>		Acylation with a C18 fatty diacid drives non-covalent binding to serum albumin, slowing renal clearance and DPP-4 access. The Aib8 substitution renders the peptide DPP-4-resistant. Resulting terminal half-life ~165 h means once-weekly subcutaneous dosing produces near-steady-state plasma levels.<ref name="lau2015"/>

	Oral semaglutide (Rybelsus) is co-formulated with '''SNAC''' (sodium N-[8-(2-hydroxybenzoyl)amino]caprylate), a permeation enhancer that transiently raises gastric pH and protects the peptide locally — yielding ~0.4–1% bioavailability, which is sufficient at 14 mg daily to match Ozempic 0.5 mg weekly for glycemic effect (but not for weight loss).<ref name="rybelsus-label"/><ref name="buckley2018">Buckley ST, Bækdal TA, Vegge A et al. (2018). Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist. ''Sci Transl Med'' 10(467):eaar7047. doi:10.1126/scitranslmed.aar7047</ref> Strict fasting administration is mandatory; any concurrent food or beverage destroys absorption.<ref name="rybelsus-label"/>		Oral semaglutide (Rybelsus) is co-formulated with '''SNAC''' (sodium N-[8-(2-hydroxybenzoyl)amino]caprylate), a permeation enhancer that transiently raises gastric pH and protects the peptide locally, yielding ~0.4–1% bioavailability, which is sufficient at 14 mg daily to match Ozempic 0.5 mg weekly for glycemic effect (but not for weight loss).<ref name="rybelsus-label"/><ref name="buckley2018">Buckley ST, Bækdal TA, Vegge A et al. (2018). Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist. ''Sci Transl Med'' 10(467):eaar7047. doi:10.1126/scitranslmed.aar7047</ref> Strict fasting administration is mandatory; any concurrent food or beverage destroys absorption.<ref name="rybelsus-label"/>

	Predominantly catabolic clearance via proteolysis; renal and hepatic impairment do not require dose adjustment.<ref name="ozempic-label"/> No CYP-mediated metabolism, so the interaction profile is dominated by ''gastric emptying'' effects on other oral medicines, not pharmacokinetic competition.<ref name="ozempic-label"/>		Predominantly catabolic clearance via proteolysis; renal and hepatic impairment do not require dose adjustment.<ref name="ozempic-label"/> No CYP-mediated metabolism, so the interaction profile is dominated by ''gastric emptying'' effects on other oral medicines, not pharmacokinetic competition.<ref name="ozempic-label"/>
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	<problem ref="ckd-t2dm" author="MDElliottMD"/>		<problem ref="ckd-t2dm" author="MDElliottMD"/>

	\| dosing = <titration slug="ozempic-standard" author="MDElliottMD" title="Ozempic — standard T2DM titration">		\| dosing = <titration slug="ozempic-standard" author="MDElliottMD" title="Ozempic, standard T2DM titration">
	0.25 mg SC weekly × 4 weeks (non-therapeutic; tolerance ramp only)		0.25 mg SC weekly × 4 weeks (non-therapeutic; tolerance ramp only)
	→ 0.5 mg SC weekly × ≥4 weeks		→ 0.5 mg SC weekly × ≥4 weeks
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	→ 2 mg SC weekly (max) if needed<ref name="ozempic-label"/>		→ 2 mg SC weekly (max) if needed<ref name="ozempic-label"/>

	Slower titration is reasonable in any patient with significant GI symptoms — holding at a tolerated dose for 8–12 weeks before advancing is standard practice.		Slower titration is reasonable in any patient with significant GI symptoms, holding at a tolerated dose for 8–12 weeks before advancing is standard practice.
	</titration>		</titration>

	<titration slug="wegovy-standard" author="MDElliottMD" title="Wegovy — standard obesity titration">		<titration slug="wegovy-standard" author="MDElliottMD" title="Wegovy, standard obesity titration">
	0.25 mg SC weekly × 4 weeks		0.25 mg SC weekly × 4 weeks
	→ 0.5 mg × 4 weeks		→ 0.5 mg × 4 weeks
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	</titration>		</titration>

	<titration slug="rybelsus-standard" author="MDElliottMD" title="Rybelsus — standard oral T2DM titration">		<titration slug="rybelsus-standard" author="MDElliottMD" title="Rybelsus, standard oral T2DM titration">
	3 mg PO daily × 30 days (non-therapeutic ramp)		3 mg PO daily × 30 days (non-therapeutic ramp)
	→ 7 mg PO daily × ≥30 days		→ 7 mg PO daily × ≥30 days
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	\| effects = Subjective effects vary considerably with dose and titration speed but reliably include:		\| effects = Subjective effects vary considerably with dose and titration speed but reliably include:
	* '''Early satiety''' — meals feel "complete" at a fraction of prior intake<ref name="step1"/>		* '''Early satiety''', meals feel "complete" at a fraction of prior intake<ref name="step1"/>
	* '''Food noise quieting''' — the most commonly volunteered subjective change. Patients report that intrusive food-related thoughts simply stop.{{Citation needed}}		* '''Food noise quieting''', the most commonly volunteered subjective change. Patients report that intrusive food-related thoughts simply stop.{{Citation needed}}
	* '''Reduced alcohol craving''' — corroborated by observational and small RCT data; mechanism likely shared with food reward circuitry<ref name="wang2024">Wang W, Volkow ND, Berger NA et al. (2024). Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population. ''Nat Commun'' 15:4548. doi:10.1038/s41467-024-48780-6</ref>		* '''Reduced alcohol craving''', corroborated by observational and small RCT data; mechanism likely shared with food reward circuitry<ref name="wang2024">Wang W, Volkow ND, Berger NA et al. (2024). Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population. ''Nat Commun'' 15:4548. doi:10.1038/s41467-024-48780-6</ref>
	* '''Nausea''' — dose-dependent, worst in first 1–2 weeks of any new dose level<ref name="ozempic-label"/>		* '''Nausea''', dose-dependent, worst in first 1–2 weeks of any new dose level<ref name="ozempic-label"/>
	* '''Constipation or diarrhea''' (variable, can alternate)<ref name="ozempic-label"/>		* '''Constipation or diarrhea''' (variable, can alternate)<ref name="ozempic-label"/>
	* '''Sulfurous eructation''' (a small but very real subgroup){{Citation needed}}		* '''Sulfurous eructation''' (a small but very real subgroup){{Citation needed}}
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	\| monitoring = * Baseline: HbA1c, weight, BP, renal function, lipid panel, [[ALT]]/AST (especially for MASH problem)		\| monitoring = * Baseline: HbA1c, weight, BP, renal function, lipid panel, [[ALT]]/AST (especially for MASH problem)
	* Personal or family history of MTC or [[MEN2]] — '''contraindicated''', do not start<ref name="ozempic-label"/>		* Personal or family history of MTC or [[MEN2]], '''contraindicated''', do not start<ref name="ozempic-label"/>
	* Every 3 months for first year: HbA1c, weight, GI tolerability, signs of [[pancreatitis]] or [[gallbladder disease]]		* Every 3 months for first year: HbA1c, weight, GI tolerability, signs of [[pancreatitis]] or [[gallbladder disease]]
	* Annual: renal function, lipids		* Annual: renal function, lipids
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	* Inject SC in abdomen, thigh, or upper arm; rotate sites. Pen is single-patient, multi-dose.<ref name="ozempic-label"/>		* Inject SC in abdomen, thigh, or upper arm; rotate sites. Pen is single-patient, multi-dose.<ref name="ozempic-label"/>
	* GI side effects almost always peak in first 2–4 weeks of any new dose level, then attenuate.<ref name="ozempic-label"/>		* GI side effects almost always peak in first 2–4 weeks of any new dose level, then attenuate.<ref name="ozempic-label"/>
	* Eat smaller portions earlier in the day. Plate sizes will feel comically large after a few weeks — that is the medicine working, not a problem to fix.		* Eat smaller portions earlier in the day. Plate sizes will feel comically large after a few weeks, that is the medicine working, not a problem to fix.
	* Hydrate aggressively (volume depletion → AKI is a real risk).<ref name="ozempic-label"/>		* Hydrate aggressively (volume depletion → AKI is a real risk).<ref name="ozempic-label"/>
	* Resistance training during weight loss protects lean mass and is strongly encouraged.{{Citation needed}}		* Resistance training during weight loss protects lean mass and is strongly encouraged.{{Citation needed}}