Tirzepatide - 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:GIP receptor agonists]]		[[Category:GIP receptor agonists]]

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

2026-05-19T03:16:12Z

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

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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	* In moderate-to-severe OSA with obesity, ~50% reduction in apnea–hypopnea index at 52 wk (SURMOUNT-OSA)<ref name="surmount-osa"/>		* In moderate-to-severe OSA with obesity, ~50% reduction in apnea–hypopnea index at 52 wk (SURMOUNT-OSA)<ref name="surmount-osa"/>

	\| 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="osa-obesity" author="MDElliottMD"/>		<problem ref="osa-obesity" author="MDElliottMD"/>

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

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

2026-05-16T23:33:08Z

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 = Tirzepatide		\| generic = Tirzepatide
	\| brand = Mounjaro (T2DM), Zepbound (obesity, OSA)		\| brand = Mounjaro (T2DM), Zepbound (obesity, OSA)
	\| structure = 39-amino-acid synthetic peptide; '''dual agonist''' at the [[GIP receptor]] and [[GLP-1 receptor]]. Acylated with a C20 fatty diacid linked via γGlu-2×AEEA spacer for albumin binding → ~5-day half-life enabling weekly dosing.<ref name="coskun2018">Coskun T, Sloop KW, Loghin C et al. (2018). LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus. ''Mol Metab'' 18:3–14. doi:10.1016/j.molmet.2018.09.009</ref>		\| structure =

	\| classes = [[GLP-1 receptor agonist]] · [[GIP receptor agonist]] · [[Antidiabetic medicines\|Antidiabetic]] · [[Anti-obesity medicines\|Anti-obesity]] · "Twincretin"		\| classes = [[GLP-1 receptor agonist]] · [[GIP receptor agonist]] · [[Antidiabetic medicines\|Antidiabetic]] · [[Anti-obesity medicines\|Anti-obesity]] · "Twincretin"
	\| mechanism = ~~Activates both~~ [[GIP receptor~~\|GIP~~]] and [[GLP-1 receptor~~\|GLP-1~~]] receptors. The dual mechanism produces greater glucose-dependent insulin secretion, greater weight loss, and a somewhat improved GI tolerability profile relative to selective GLP-1 RAs in head-to-head comparison.<ref name="coskun2018"/><ref name="~~surpass2~~"~~>Frías JP et al. (2021~~). ~~Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2). ''NEJM'' 385(6):503–15. doi:10.1056/NEJMoa2107519</ref>~~		\| mechanism = Dual agonist of the [[GIP receptor]] and [[GLP-1 receptor]] ("twincretin").

	\| uses = [[Type 2 diabetes mellitus]] · [[Obesity]] · [[Obstructive sleep apnea]] in obesity		\| uses = [[Type 2 diabetes mellitus]] · [[Obesity]] · [[Obstructive sleep apnea]] in obesity
	\| starting_dose = 2.5 mg SC weekly × 4 wk (non-therapeutic ramp)<ref name="mounjaro-label">US FDA. ''Mounjaro (tirzepatide) prescribing information.'' Eli Lilly. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215866s000lbl.pdf</ref>		\| starting_dose = 2.5 mg SC weekly × 4 wk (non-therapeutic ramp)<ref name="mounjaro-label">US FDA. ''Mounjaro (tirzepatide) prescribing information.'' Eli Lilly. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215866s000lbl.pdf</ref>
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	\| halflife = ~5 days (~120 h)<ref name="mounjaro-label"/>		\| halflife = ~5 days (~120 h)<ref name="mounjaro-label"/>
	\| bioavailability = SC ~80%{{Citation needed}}		\| bioavailability = SC ~80%{{Citation needed}}
	\| pregnancy = Avoid. Discontinue ≥1 month ~~before planned pregnancy due to long half~~-~~life~~. ~~Animal data show embryofetal harm.<ref name="mounjaro-label"/>~~ May reduce efficacy ~~of oral contraceptives (delayed gastric emptying) — non-oral or barrier contraception advised, particularly~~ during ~~dose escalation~~.<ref name="mounjaro-label"/>		\| pregnancy = Avoid. Discontinue ≥1 month pre-conception. May reduce oral contraceptive efficacy during titration.<ref name="mounjaro-label"/>

	\| legal = Rx-only;<ref name="mounjaro-label"/> not a controlled substance		\| legal = Rx-only;<ref name="mounjaro-label"/> not a controlled substance
	\| intro = Tirzepatide is the first '''dual GIP / GLP-1 receptor agonist''' ("twincretin") approved for clinical use. Eli Lilly markets it as '''[[Mounjaro]]''' (for [[type 2 diabetes mellitus]], FDA-approved May 2022)<ref name="mounjaro-label"/> and '''[[Zepbound]]''' (for [[obesity]], November 2023;<ref name="zepbound-label"/> later expanded to [[obstructive sleep apnea]] in obesity in December 2024<ref name="surmount-osa">Malhotra A, Grunstein RR, Fietze I et al. (2024). Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA). ''NEJM'' 391(13):1193–205. doi:10.1056/NEJMoa2404881</ref>).		\| intro = Tirzepatide is the first '''dual GIP / GLP-1 receptor agonist''' ("twincretin") approved for clinical use. Eli Lilly markets it as '''[[Mounjaro]]''' (for [[type 2 diabetes mellitus]], FDA-approved May 2022)<ref name="mounjaro-label"/> and '''[[Zepbound]]''' (for [[obesity]], November 2023;<ref name="zepbound-label"/> later expanded to [[obstructive sleep apnea]] in obesity in December 2024<ref name="surmount-osa">Malhotra A, Grunstein RR, Fietze I et al. (2024). Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA). ''NEJM'' 391(13):1193–205. doi:10.1056/NEJMoa2404881</ref>).
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	In direct comparison, tirzepatide produced greater HbA1c reduction and greater weight loss than [[semaglutide]] at maximum approved doses (SURPASS-2),<ref name="surpass2"/> and the largest weight loss yet reported with an injectable incretin in obesity without diabetes — up to ~22.5% body weight at 72 weeks (SURMOUNT-1).<ref name="surmount1"/>		In direct comparison, tirzepatide produced greater HbA1c reduction and greater weight loss than [[semaglutide]] at maximum approved doses (SURPASS-2),<ref name="surpass2"/> and the largest weight loss yet reported with an injectable incretin in obesity without diabetes — up to ~22.5% body weight at 72 weeks (SURMOUNT-1).<ref name="surmount1"/>

	\| pharmacokinetics = Acylation with a C20 fatty diacid drives non-covalent albumin binding, producing a terminal half-life of ~120 hours and supporting once-weekly subcutaneous dosing.<ref name="coskun2018"/><ref name="mounjaro-label"/> Cleared predominantly by proteolytic catabolism; no CYP-mediated metabolism. Renal and hepatic impairment do not require dose adjustment.<ref name="mounjaro-label"/>		\| pharmacokinetics = '''Chemistry'''. 39-amino-acid synthetic peptide; '''dual agonist''' at the [[GIP receptor]] and [[GLP-1 receptor]]. Acylated with a C20 fatty diacid linked via γGlu-2×AEEA spacer for albumin binding → ~5-day half-life enabling weekly dosing.<ref name="coskun2018">Coskun T, Sloop KW, Loghin C et al. (2018). LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus. ''Mol Metab'' 18:3–14. doi:10.1016/j.molmet.2018.09.009</ref>

			Acylation with a C20 fatty diacid drives non-covalent albumin binding, producing a terminal half-life of ~120 hours and supporting once-weekly subcutaneous dosing.<ref name="coskun2018"/><ref name="mounjaro-label"/> Cleared predominantly by proteolytic catabolism; no CYP-mediated metabolism. Renal and hepatic impairment do not require dose adjustment.<ref name="mounjaro-label"/>

	Delayed gastric emptying is greatest during dose escalation and attenuates over time. This can reduce absorption of co-administered oral medicines, including oral contraceptives — clinically relevant during the first 4 weeks of any new dose level.<ref name="mounjaro-label"/>		Delayed gastric emptying is greatest during dose escalation and attenuates over time. This can reduce absorption of co-administered oral medicines, including oral contraceptives — clinically relevant during the first 4 weeks of any new dose level.<ref name="mounjaro-label"/>

	\| pharmacodynamics = At the 15 mg/wk maintenance dose:		\| pharmacodynamics = '''Receptor pharmacology'''. Activates both [[GIP receptor\|GIP]] and [[GLP-1 receptor\|GLP-1]] receptors. The dual mechanism produces greater glucose-dependent insulin secretion, greater weight loss, and a somewhat improved GI tolerability profile relative to selective GLP-1 RAs in head-to-head comparison.<ref name="coskun2018"/><ref name="surpass2">Frías JP et al. (2021). Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2). ''NEJM'' 385(6):503–15. doi:10.1056/NEJMoa2107519</ref>

			At the 15 mg/wk maintenance dose:
	* HbA1c reduction of ~2.0–2.3 percentage points in T2DM<ref name="surpass2"/>		* HbA1c reduction of ~2.0–2.3 percentage points in T2DM<ref name="surpass2"/>
	* Weight loss of ~22.5% body weight at 72 wk in obesity without T2DM (SURMOUNT-1)<ref name="surmount1"/>		* Weight loss of ~22.5% body weight at 72 wk in obesity without T2DM (SURMOUNT-1)<ref name="surmount1"/>

MDElliottMD: Create Tirzepatide page (initial draft, MedTemplate, full inline cites)

2026-05-16T23:11:34Z

Create Tirzepatide page (initial draft, MedTemplate, full inline cites)

New page

{{MedTemplate
| generic = Tirzepatide
| brand = Mounjaro (T2DM), Zepbound (obesity, OSA)
| structure = 39-amino-acid synthetic peptide; '''dual agonist''' at the [[GIP receptor]] and [[GLP-1 receptor]]. Acylated with a C20 fatty diacid linked via γGlu-2×AEEA spacer for albumin binding → ~5-day half-life enabling weekly dosing.<ref name="coskun2018">Coskun T, Sloop KW, Loghin C et al. (2018). LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus. ''Mol Metab'' 18:3–14. doi:10.1016/j.molmet.2018.09.009</ref>
| classes = [[GLP-1 receptor agonist]] · [[GIP receptor agonist]] · [[Antidiabetic medicines|Antidiabetic]] · [[Anti-obesity medicines|Anti-obesity]] · "Twincretin"
| mechanism = Activates both [[GIP receptor|GIP]] and [[GLP-1 receptor|GLP-1]] receptors. The dual mechanism produces greater glucose-dependent insulin secretion, greater weight loss, and a somewhat improved GI tolerability profile relative to selective GLP-1 RAs in head-to-head comparison.<ref name="coskun2018"/><ref name="surpass2">Frías JP et al. (2021). Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2). ''NEJM'' 385(6):503–15. doi:10.1056/NEJMoa2107519</ref>
| uses = [[Type 2 diabetes mellitus]] · [[Obesity]] · [[Obstructive sleep apnea]] in obesity
| starting_dose = 2.5 mg SC weekly × 4 wk (non-therapeutic ramp)<ref name="mounjaro-label">US FDA. ''Mounjaro (tirzepatide) prescribing information.'' Eli Lilly. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215866s000lbl.pdf</ref>
| preparations = Pre-filled single-dose pen and vial: 2.5 / 5 / 7.5 / 10 / 12.5 / 15 mg<ref name="mounjaro-label"/><ref name="zepbound-label">US FDA. ''Zepbound (tirzepatide) prescribing information.'' Eli Lilly. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217806s000lbl.pdf</ref>
| fda_max = 15 mg/wk SC<ref name="mounjaro-label"/><ref name="zepbound-label"/>
| routes = Subcutaneous (abdomen, thigh, upper arm)<ref name="mounjaro-label"/>
| onset = Glycemic effect within days; full weight effect over months<ref name="surmount1">Jastreboff AM et al. (2022). Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). ''NEJM'' 387:205–16. doi:10.1056/NEJMoa2206038</ref>
| duration = ~7 days (weekly dosing)<ref name="mounjaro-label"/>
| halflife = ~5 days (~120 h)<ref name="mounjaro-label"/>
| bioavailability = SC ~80%{{Citation needed}}
| pregnancy = Avoid. Discontinue ≥1 month before planned pregnancy due to long half-life. Animal data show embryofetal harm.<ref name="mounjaro-label"/> May reduce efficacy of oral contraceptives (delayed gastric emptying) — non-oral or barrier contraception advised, particularly during dose escalation.<ref name="mounjaro-label"/>
| legal = Rx-only;<ref name="mounjaro-label"/> not a controlled substance
| intro = Tirzepatide is the first '''dual GIP / GLP-1 receptor agonist''' ("twincretin") approved for clinical use. Eli Lilly markets it as '''[[Mounjaro]]''' (for [[type 2 diabetes mellitus]], FDA-approved May 2022)<ref name="mounjaro-label"/> and '''[[Zepbound]]''' (for [[obesity]], November 2023;<ref name="zepbound-label"/> later expanded to [[obstructive sleep apnea]] in obesity in December 2024<ref name="surmount-osa">Malhotra A, Grunstein RR, Fietze I et al. (2024). Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA). ''NEJM'' 391(13):1193–205. doi:10.1056/NEJMoa2404881</ref>).

In direct comparison, tirzepatide produced greater HbA1c reduction and greater weight loss than [[semaglutide]] at maximum approved doses (SURPASS-2),<ref name="surpass2"/> and the largest weight loss yet reported with an injectable incretin in obesity without diabetes — up to ~22.5% body weight at 72 weeks (SURMOUNT-1).<ref name="surmount1"/>

| pharmacokinetics = Acylation with a C20 fatty diacid drives non-covalent albumin binding, producing a terminal half-life of ~120 hours and supporting once-weekly subcutaneous dosing.<ref name="coskun2018"/><ref name="mounjaro-label"/> Cleared predominantly by proteolytic catabolism; no CYP-mediated metabolism. Renal and hepatic impairment do not require dose adjustment.<ref name="mounjaro-label"/>

Delayed gastric emptying is greatest during dose escalation and attenuates over time. This can reduce absorption of co-administered oral medicines, including oral contraceptives — clinically relevant during the first 4 weeks of any new dose level.<ref name="mounjaro-label"/>

| pharmacodynamics = At the 15 mg/wk maintenance dose:
* HbA1c reduction of ~2.0–2.3 percentage points in T2DM<ref name="surpass2"/>
* Weight loss of ~22.5% body weight at 72 wk in obesity without T2DM (SURMOUNT-1)<ref name="surmount1"/>
* In T2DM with obesity, ~15.7% weight loss at 72 wk (SURMOUNT-2)<ref name="surmount2">Garvey WT, Frias JP, Jastreboff AM et al. (2023). Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2). ''Lancet'' 402(10402):613–26. doi:10.1016/S0140-6736(23)01200-X</ref>
* In moderate-to-severe OSA with obesity, ~50% reduction in apnea–hypopnea index at 52 wk (SURMOUNT-OSA)<ref name="surmount-osa"/>

| indications = <indication ref="diabetes-type-2" author="MDElliottMD"/>
<indication ref="obesity" author="MDElliottMD"/>
<indication ref="osa-obesity" author="MDElliottMD"/>

| dosing = <titration slug="mounjaro-standard" author="MDElliottMD" title="Mounjaro — standard T2DM titration">
2.5 mg SC weekly × 4 weeks (non-therapeutic ramp)
→ 5 mg SC weekly × ≥4 weeks
→ 7.5 mg weekly × ≥4 weeks if needed
→ 10 mg weekly × ≥4 weeks if needed
→ 12.5 mg weekly × ≥4 weeks if needed
→ 15 mg weekly (max)<ref name="mounjaro-label"/>

Hold at any tolerated dose if response is adequate. Slow titration is preferred in any patient with significant GI symptoms — holding 8–12 weeks before advancing is reasonable.
</titration>

<titration slug="zepbound-standard" author="MDElliottMD" title="Zepbound — standard obesity titration">
2.5 mg SC weekly × 4 weeks (non-therapeutic ramp)
→ 5 mg SC weekly × ≥4 weeks
→ 7.5 mg → 10 mg → 12.5 mg → 15 mg weekly (max), each step held ≥4 weeks<ref name="zepbound-label"/>

Maintenance is generally 5, 10, or 15 mg/wk depending on response and tolerability. The intermediate steps (7.5 / 12.5 mg) exist to ease titration but are not typical maintenance doses.
</titration>

| effects = * '''Early satiety''' and reduced food intake<ref name="surmount1"/>
* '''Food noise quieting''' (also reported with semaglutide){{Citation needed}}
* '''Nausea''' — dose-dependent, worst during titration steps<ref name="mounjaro-label"/>
* '''Constipation or diarrhea''' (variable)<ref name="mounjaro-label"/>
* '''Decreased appetite''' (clinically the desired effect)<ref name="mounjaro-label"/>
* '''Injection-site reactions''' — uncommon, generally mild<ref name="mounjaro-label"/>

GI tolerability appears modestly better than selective GLP-1 RAs at comparable HbA1c / weight-loss endpoints,{{Citation needed}} possibly reflecting the additional GIP-receptor activity.

| interactions = <pharmaInteractions/>

| pregnancy_details = Avoid. Animal embryofetal toxicity is documented.<ref name="mounjaro-label"/> Discontinue ≥1 month before planned conception. Clinically important interaction: tirzepatide reduces absorption of oral contraceptives during initiation and dose escalation — counsel patients to switch to a non-oral or barrier method for at least the first 4 weeks of each new dose level.<ref name="mounjaro-label"/>

| monitoring = * Baseline: HbA1c, weight, BP, renal function, lipid panel
* Personal or family history of MTC or [[MEN2]] — '''contraindicated''', do not start<ref name="mounjaro-label"/>
* Every 3 months for first year: HbA1c, weight, GI tolerability, signs of [[pancreatitis]] or [[gallbladder disease]]<ref name="mounjaro-label"/>
* Annual: renal function, lipids
* '''Pre-procedure''': hold weekly dose ≥7 days before any planned anesthesia (per [[American Society of Anesthesiologists|ASA]] 2024 guidance)<ref name="kindel2024">Kindel TL et al. (2024). Perioperative GLP-1 receptor agonist safety guidance. ''Surg Obes Relat Dis'' 20(12):1183–8.</ref>

| counseling = * '''Slow titration''' is non-negotiable.
* Inject SC in abdomen, thigh, or upper arm; rotate sites.<ref name="mounjaro-label"/>
* GI side effects peak in the first 2–4 weeks of each new dose level, then attenuate.
* '''Oral contraceptives''': switch to a non-oral / barrier method for at least 4 weeks after starting and after each dose escalation.<ref name="mounjaro-label"/>
* Hydrate aggressively (volume depletion → AKI is a real risk).<ref name="mounjaro-label"/>
* Resistance training during weight loss protects lean mass.{{Citation needed}}
* If a weekly dose is missed: take within 4 days; if >4 days, skip and resume on the next regular day.<ref name="mounjaro-label"/>
* '''Surgery''': hold dose 7 days pre-op and tell every anesthesiologist.<ref name="kindel2024"/>
* '''Pregnancy planning''': stop ≥1 month before trying to conceive.<ref name="mounjaro-label"/>

| anecdotes = <vote slug="tirzepatide-vs-semaglutide"/>
<vote slug="food-noise"/>

| seealso = [[GLP-1 receptor agonist]] · [[Semaglutide]] · [[Liraglutide]] · [[Dulaglutide]] · [[Exenatide]] · [[Type 2 diabetes mellitus]] · [[Obesity]] · [[Obstructive sleep apnea]]

| references = <references/>
}}

[[Category:MedCategory]]
[[Category:GLP-1 receptor agonists]]
[[Category:GIP receptor agonists]]
[[Category:Antidiabetic medicines]]
[[Category:Anti-obesity medicines]]
[[Category:Eli Lilly medicines]]

← Older revision		Revision as of 03:16, 19 May 2026
Line 21:		Line 21:
	\| intro = Tirzepatide is the first '''dual GIP / GLP-1 receptor agonist''' ("twincretin") approved for clinical use. Eli Lilly markets it as '''[[Mounjaro]]''' (for [[type 2 diabetes mellitus]], FDA-approved May 2022)<ref name="mounjaro-label"/> and '''[[Zepbound]]''' (for [[obesity]], November 2023;<ref name="zepbound-label"/> later expanded to [[obstructive sleep apnea]] in obesity in December 2024<ref name="surmount-osa">Malhotra A, Grunstein RR, Fietze I et al. (2024). Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA). ''NEJM'' 391(13):1193–205. doi:10.1056/NEJMoa2404881</ref>).		\| intro = Tirzepatide is the first '''dual GIP / GLP-1 receptor agonist''' ("twincretin") approved for clinical use. Eli Lilly markets it as '''[[Mounjaro]]''' (for [[type 2 diabetes mellitus]], FDA-approved May 2022)<ref name="mounjaro-label"/> and '''[[Zepbound]]''' (for [[obesity]], November 2023;<ref name="zepbound-label"/> later expanded to [[obstructive sleep apnea]] in obesity in December 2024<ref name="surmount-osa">Malhotra A, Grunstein RR, Fietze I et al. (2024). Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA). ''NEJM'' 391(13):1193–205. doi:10.1056/NEJMoa2404881</ref>).

	In direct comparison, tirzepatide produced greater HbA1c reduction and greater weight loss than [[semaglutide]] at maximum approved doses (SURPASS-2),<ref name="surpass2"/> and the largest weight loss yet reported with an injectable incretin in obesity without diabetes — up to ~22.5% body weight at 72 weeks (SURMOUNT-1).<ref name="surmount1"/>		In direct comparison, tirzepatide produced greater HbA1c reduction and greater weight loss than [[semaglutide]] at maximum approved doses (SURPASS-2),<ref name="surpass2"/> and the largest weight loss yet reported with an injectable incretin in obesity without diabetes, up to ~22.5% body weight at 72 weeks (SURMOUNT-1).<ref name="surmount1"/>

	\| pharmacokinetics = '''Chemistry'''. 39-amino-acid synthetic peptide; '''dual agonist''' at the [[GIP receptor]] and [[GLP-1 receptor]]. Acylated with a C20 fatty diacid linked via γGlu-2×AEEA spacer for albumin binding → ~5-day half-life enabling weekly dosing.<ref name="coskun2018">Coskun T, Sloop KW, Loghin C et al. (2018). LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus. ''Mol Metab'' 18:3–14. doi:10.1016/j.molmet.2018.09.009</ref>		\| pharmacokinetics = '''Chemistry'''. 39-amino-acid synthetic peptide; '''dual agonist''' at the [[GIP receptor]] and [[GLP-1 receptor]]. Acylated with a C20 fatty diacid linked via γGlu-2×AEEA spacer for albumin binding → ~5-day half-life enabling weekly dosing.<ref name="coskun2018">Coskun T, Sloop KW, Loghin C et al. (2018). LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus. ''Mol Metab'' 18:3–14. doi:10.1016/j.molmet.2018.09.009</ref>
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	Acylation with a C20 fatty diacid drives non-covalent albumin binding, producing a terminal half-life of ~120 hours and supporting once-weekly subcutaneous dosing.<ref name="coskun2018"/><ref name="mounjaro-label"/> Cleared predominantly by proteolytic catabolism; no CYP-mediated metabolism. Renal and hepatic impairment do not require dose adjustment.<ref name="mounjaro-label"/>		Acylation with a C20 fatty diacid drives non-covalent albumin binding, producing a terminal half-life of ~120 hours and supporting once-weekly subcutaneous dosing.<ref name="coskun2018"/><ref name="mounjaro-label"/> Cleared predominantly by proteolytic catabolism; no CYP-mediated metabolism. Renal and hepatic impairment do not require dose adjustment.<ref name="mounjaro-label"/>

	Delayed gastric emptying is greatest during dose escalation and attenuates over time. This can reduce absorption of co-administered oral medicines, including oral contraceptives — clinically relevant during the first 4 weeks of any new dose level.<ref name="mounjaro-label"/>		Delayed gastric emptying is greatest during dose escalation and attenuates over time. This can reduce absorption of co-administered oral medicines, including oral contraceptives, clinically relevant during the first 4 weeks of any new dose level.<ref name="mounjaro-label"/>

	\| pharmacodynamics = '''Receptor pharmacology'''. Activates both [[GIP receptor\|GIP]] and [[GLP-1 receptor\|GLP-1]] receptors. The dual mechanism produces greater glucose-dependent insulin secretion, greater weight loss, and a somewhat improved GI tolerability profile relative to selective GLP-1 RAs in head-to-head comparison.<ref name="coskun2018"/><ref name="surpass2">Frías JP et al. (2021). Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2). ''NEJM'' 385(6):503–15. doi:10.1056/NEJMoa2107519</ref>		\| pharmacodynamics = '''Receptor pharmacology'''. Activates both [[GIP receptor\|GIP]] and [[GLP-1 receptor\|GLP-1]] receptors. The dual mechanism produces greater glucose-dependent insulin secretion, greater weight loss, and a somewhat improved GI tolerability profile relative to selective GLP-1 RAs in head-to-head comparison.<ref name="coskun2018"/><ref name="surpass2">Frías JP et al. (2021). Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2). ''NEJM'' 385(6):503–15. doi:10.1056/NEJMoa2107519</ref>
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	<problem ref="osa-obesity" author="MDElliottMD"/>		<problem ref="osa-obesity" author="MDElliottMD"/>

	\| dosing = <titration slug="mounjaro-standard" author="MDElliottMD" title="Mounjaro — standard T2DM titration">		\| dosing = <titration slug="mounjaro-standard" author="MDElliottMD" title="Mounjaro, standard T2DM titration">
	2.5 mg SC weekly × 4 weeks (non-therapeutic ramp)		2.5 mg SC weekly × 4 weeks (non-therapeutic ramp)
	→ 5 mg SC weekly × ≥4 weeks		→ 5 mg SC weekly × ≥4 weeks
Line 49:		Line 49:
	→ 15 mg weekly (max)<ref name="mounjaro-label"/>		→ 15 mg weekly (max)<ref name="mounjaro-label"/>

	Hold at any tolerated dose if response is adequate. Slow titration is preferred in any patient with significant GI symptoms — holding 8–12 weeks before advancing is reasonable.		Hold at any tolerated dose if response is adequate. Slow titration is preferred in any patient with significant GI symptoms, holding 8–12 weeks before advancing is reasonable.
	</titration>		</titration>

	<titration slug="zepbound-standard" author="MDElliottMD" title="Zepbound — standard obesity titration">		<titration slug="zepbound-standard" author="MDElliottMD" title="Zepbound, standard obesity titration">
	2.5 mg SC weekly × 4 weeks (non-therapeutic ramp)		2.5 mg SC weekly × 4 weeks (non-therapeutic ramp)
	→ 5 mg SC weekly × ≥4 weeks		→ 5 mg SC weekly × ≥4 weeks
Line 62:		Line 62:
	\| effects = * '''Early satiety''' and reduced food intake<ref name="surmount1"/>		\| effects = * '''Early satiety''' and reduced food intake<ref name="surmount1"/>
	* '''Food noise quieting''' (also reported with semaglutide){{Citation needed}}		* '''Food noise quieting''' (also reported with semaglutide){{Citation needed}}
	* '''Nausea''' — dose-dependent, worst during titration steps<ref name="mounjaro-label"/>		* '''Nausea''', dose-dependent, worst during titration steps<ref name="mounjaro-label"/>
	* '''Constipation or diarrhea''' (variable)<ref name="mounjaro-label"/>		* '''Constipation or diarrhea''' (variable)<ref name="mounjaro-label"/>
	* '''Decreased appetite''' (clinically the desired effect)<ref name="mounjaro-label"/>		* '''Decreased appetite''' (clinically the desired effect)<ref name="mounjaro-label"/>
	* '''Injection-site reactions''' — uncommon, generally mild<ref name="mounjaro-label"/>		* '''Injection-site reactions''', uncommon, generally mild<ref name="mounjaro-label"/>

	GI tolerability appears modestly better than selective GLP-1 RAs at comparable HbA1c / weight-loss endpoints,{{Citation needed}} possibly reflecting the additional GIP-receptor activity.		GI tolerability appears modestly better than selective GLP-1 RAs at comparable HbA1c / weight-loss endpoints,{{Citation needed}} possibly reflecting the additional GIP-receptor activity.
Line 71:		Line 71:
	\| interactions = <pharmaInteractions/>		\| interactions = <pharmaInteractions/>

	\| pregnancy_details = Avoid. Animal embryofetal toxicity is documented.<ref name="mounjaro-label"/> Discontinue ≥1 month before planned conception. Clinically important interaction: tirzepatide reduces absorption of oral contraceptives during initiation and dose escalation — counsel patients to switch to a non-oral or barrier method for at least the first 4 weeks of each new dose level.<ref name="mounjaro-label"/>		\| pregnancy_details = Avoid. Animal embryofetal toxicity is documented.<ref name="mounjaro-label"/> Discontinue ≥1 month before planned conception. Clinically important interaction: tirzepatide reduces absorption of oral contraceptives during initiation and dose escalation, counsel patients to switch to a non-oral or barrier method for at least the first 4 weeks of each new dose level.<ref name="mounjaro-label"/>

	\| monitoring = * Baseline: HbA1c, weight, BP, renal function, lipid panel		\| monitoring = * Baseline: HbA1c, weight, BP, renal function, lipid panel
	* Personal or family history of MTC or [[MEN2]] — '''contraindicated''', do not start<ref name="mounjaro-label"/>		* Personal or family history of MTC or [[MEN2]], '''contraindicated''', do not start<ref name="mounjaro-label"/>
	* Every 3 months for first year: HbA1c, weight, GI tolerability, signs of [[pancreatitis]] or [[gallbladder disease]]<ref name="mounjaro-label"/>		* Every 3 months for first year: HbA1c, weight, GI tolerability, signs of [[pancreatitis]] or [[gallbladder disease]]<ref name="mounjaro-label"/>
	* Annual: renal function, lipids		* Annual: renal function, lipids