1. Indlela yokuSebenza
I-Glucagon-like peptide-1 (GLP-1)yiincretin hormoneikhutshwe ngamathumbu e-L-cells ekuphenduleni ukutya. I-GLP-1 receptor agonists (GLP-1 RAs) ilinganisa iziphumo ze-hormone ye-physiological ngokusebenzisa iindlela ezininzi ze-metabolic:
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Ukunyanzelwa kokutya kunye nokuLityaziswa kokukhutshwa kwesisu
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Yenza kumaziko e-hypothalamic satiety (ngokukodwa i-POMC / CART neurons), ukunciphisa indlala.
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Ukukhupha isisu esicothayo, ukwandisa imvakalelo yokuhlutha.
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Ukukhutshwa kwe-insulin eyongeziweyo kunye nokuNcitshiswa kweGlucagon
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Ukuvuselela iiseli ze-pancreatic β-cell ukukhupha i-insulin ngendlela exhomekeke kwi-glucose.
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Ukuxinzelela i-glucagon secretion, ukuphucula kokubili ukuzila kunye namanqanaba eglucose emva kokutya.
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Ukuphuculwa kwamandla eMetabolism
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Ukwandisa uvakalelo lwe-insulin kunye nokukhuthaza i-oxidation yamafutha.
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Ukunciphisa i-fat hepatic synthesis kunye nokuphucula i-lipid metabolism.
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2. I-Key GLP-1–Ii-Arhente zokuLahla kobunzima
| Iziyobisi | Isalathiso esingundoqo | Ulawulo | I-Avareji yokunciphisa umzimba |
|---|---|---|---|
| ILiraglutide | Uhlobo lwe-2 yeswekile, ukutyeba | Isitofu semihla ngemihla | 5–8% |
| Semaglutide | Uhlobo lwe-2 yeswekile, ukutyeba | Inaliti yeveki / yomlomo | 10–15% |
| Tirzepatide | Uhlobo lwe-2 yeswekile, ukutyeba | Isitofu seveki | 15–22% |
| Retatrutide (kwizilingo) | Ukutyeba kakhulu (okungeyosifo seswekile) | Isitofu seveki | Ukuya kuthi ga kwi-24% |
Indlela:I-Drug evolution iqhubela phambili ukusuka kwi-agonist eyodwa ye-GLP-1 ye-receptor → ii-agonists ezimbini ze-GIP/GLP-1 → ii-agonists ezintathu (GIP/GLP-1/GCGR).
3. Iimvavanyo ezingundoqo zeklinikhi kunye neziphumo
I-Semaglutide - Izilingo ze-STEP
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INYATHELO 1 (NEJM, 2021)
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Abathathi-nxaxheba: Abantu abadala abatyebileyo, abangenaso isifo seswekile
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Idosi: 2.4 mg ngeveki (i-subcutaneous)
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Iziphumo: Ukunciphisa ubunzima bomzimba14.9%kwiiveki ze-68 vs. 2.4% kunye ne-placebo
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~ I-33% yabathathi-nxaxheba baphumelele ≥20% ukulahleka kwesisindo.
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INYATHELO 5 (2022)
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Kubonakaliswe ukulahleka kobunzima obuqhubekayo kwiminyaka eyi-2 kunye nokuphuculwa kwezinto ezinobungozi be-cardiometabolic.
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I-Tirzepatide – SURMOUNT & SURPASS Programme
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SURMOUNT-1 (NEJM, 2022)
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Abathathi-nxaxheba: Abantu abadala abatyebileyo, abangenaso isifo seswekile
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Umthamo: 5 mg, 10 mg, 15 mg ngeveki
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Iziphumo: Kuthetha ukwehla kobunzima15–21%emva kweeveki ezingama-72 (kuxhomekeke kwidosi)
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Phantse i-40% iphumelele ≥25% ukunciphisa ubunzima.
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Uvavanyo lwe-SURPASS (abemi abanesifo seswekile)
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Ukunciphisa i-HbA1c: ukuya kuthi ga2.2%
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Ukwehla kobunzima obuqhelekileyo obulinganayo10–15%.
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4. Impilo eyongezelelweyo kunye neeNzuzo zeMetabolic
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Ukunciphisa kwiifuthe legazi, I-LDL-cholesterol, kwayetriglycerides
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Yehlisiwei-visceralkwayeamafutha hepatic(ukuphuculwa kwe-NAFLD)
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Umngcipheko ophantsi weiziganeko zentliziyo(umz., MI, stroke)
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Ukuqhubela phambili okulibazisekayo ukusuka kwi-prediabetes ukuya kuhlobo lwe-2 yeswekile
5. Iprofayili yoKhuseleko kunye neNgqwalasela
Iziphumo ebezingalindelekanga eziqhelekileyo (ngokuqhelekileyo ziphakathi ukuya phakathi):
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Isicaphucaphu, ukugabha, ukuqunjelwa, ukuqunjelwa
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Ukulahlekelwa ngumdla
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Ukungakhululeki kwesisu sexeshana
Izilumkiso / izithintelo:
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Imbali ye-pancreatitis okanye i-medullary thyroid carcinoma
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Ukukhulelwa kunye nokuncancisa
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Ithamo kancinane ithitration icetyiswa ukuphucula ukunyamezeleka
6. Izikhokelo zoPhando lwexesha elizayo
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Isizukulwana esilandelayo ii-agonists ezininzi:
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Ii-agonists ezintathu ezijolise kwi-GIP/GLP-1/GCGR (umz.,Retatrutide)
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Ukwenziwa ngomlomo kwe-GLP-1:
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Umthamo ophezulu we-semaglutide yomlomo (ukuya kwi-50 mg) phantsi kovavanyo
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Unyango oludityanisiweyo:
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I-GLP-1 + i-insulin okanye i-SGLT2 inhibitors
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Iimpawu ezibanzi zemetabolism:
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Isifo sesibindi esinamafutha e-non-alcoholic (NAFLD), i-polycystic ovary syndrome (PCOS), i-apnea yokulala, ukukhusela kwi-cardiovascular
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7. Isiphelo
Amachiza asekelwe kwi-GLP-1 amele utshintsho lweparadigm ukusuka kulawulo lweswekile ukuya kulawulo olupheleleyo lwemetabolism kunye nobunzima.
Kunye neearhente ezifanaSemaglutidekwayeTirzepatide, ukulahleka kwesisindo esingekho utyando ngaphezu kwe-20% kuye kwafezekiswa.
Ii-agonists zexesha elizayo ze-multi-receptor kulindeleke ukuba ziqhubele phambili ukuphucula ukusebenza, ukuqina, kunye neenzuzo ze-cardiometabolic.
Ixesha lokuposa: Oct-11-2025