ʻO ke kuleana a me kahi o dapagliflozin i ka hoʻokele o ka maʻi diabetes mellitus type 2: mai ka ʻatikua a hoʻomaʻamaʻa ʻatikala o kahi ʻepekema ʻepekema i ka mea kūikawā - ʻo ka lāʻau lapaʻau a me ka mālama ola.

Kūkulu ʻia kahi ala hou i ka mālama ʻana o ka maʻi mellitus type type 2 (T2DM) i ka glucosuria i loaʻa i ka lāʻau a me ka hoʻohaʻahaʻa ʻana i ka paepae o ka renal o ka glucose, a me nā lāʻau lapaʻau me kahi ʻano like ʻole e pili ana i ka papa hou o nā hana hypoglycemic: type 2 sodium glucose cotransporter inhibitors (NGLT) 2). Ma kahi o ka hoʻomaikaʻi ʻana i ka mana glycemic, ua kōkua nā NGLT-2 i ka hōʻemi ʻana i ka momona o ke kino a me ke koko (BP), hoʻonui i ka hoʻonaninani ʻana i ka iwi a me ka hoʻomaikaʻi i ka hana β-cell. ʻO Dapagliflozin ka mea mālama pilikino o NGLT-2, ka mea, ma muli o kāna ʻano hana kūʻokoʻa o ka hana o ka insulin, he palena liʻiliʻi loa o ka hypoglycemia hoʻohālikelike i ka lāʻau lapaʻau maʻi maʻamau e like me ka sulfonylurea a me ka insulin. No kēia kumu, he hiki i kā dapagliflozin ke ʻano pono me ka hui pū me nā huaʻōlelo hypoglycemic oral (PSSP). Eia kekahi, ma muli o kāna hopena natriuretic a me ka hiki ke hoʻemi i ke kaumaha o ke kino a me ke koko, ʻo dapagliflozin ka lāʻau lapaʻau e koho ai i nā mea maʻi me ka maʻi type type 2 a me nā maʻi cardiovascular o ka hopena atherosclerotic. ʻO ka hui pūʻana o nā pono kūpono, ʻo ia hoʻi kahi kōpana palekana palekana o dapagliflozin, hiki iā ia ke hoʻohana nui i kēia lāʻau lapaʻau i ka hoʻomaka a me ka hoʻoikaika ʻana o ka mālama maʻi no ka T2DM.

ROLO MA KA LOA ʻO DAPAGLIFLOZIN I KA MANAWA ʻO ka 2 O kā TYPE DIABETES: Mai ka ʻĀwau ʻana e hana ai i ka hana.

Ke ala hou loa e pili ana i ka mālama ʻana o ka mellitus Type 2 type mellitus (T2DM) e pili ana i ka glycosuria i ke ʻano o ka lāʻau a me ka hoʻohaʻahaʻa ʻana i ka paepae o ka huehue o ka glucose, a me nā lāʻau lapaʻau me kahi ʻano like ʻole e pili ana i ka hana hou ʻana i nā hana me nā mea hana. ʻO nā cotransporter glucose (GLT-2). Ma kahi o ka hoʻomaikaʻi ʻana i ka mana glycemic control SGCT-2 inhibitors ke hoʻouluulu nei i ka hoʻolilo nui ʻana a me ka hoʻokahe koko (BP), i hoʻonui nui ʻia i nā ʻine a me ka hoʻomaikaʻi ʻana i ka hana β-cell. ʻO Dapagliflozin ka mea paʻa o ka SGCT-2 inhibitor, ka mea i kū i ka hana kūʻokoʻa o ka insulin o ka hana e hōʻike ana i ka hopena o ka liʻiliʻi o ka hypoglycemia e hoʻohālikelike ʻia i nā lāʻau anti> mau mea kanu, e like me ka sulfonylurea a me ka insulin. No kēia kumu, loaʻa i ka lāʻau lapaʻau ka hiki ke hoʻohui pū me nā lako ʻē aʻe hypoglycemic agents (OHGA). Eia kekahi, ma muli o kāna hopena natriuretic a me ka hiki ke hoʻemi i ke kaumaha o ke kino a me ke koko dapagliflozin ke ʻano o ke koho pono i nā mea maʻi me T2DM a me nā maʻi cardiovascular o ka maʻi gomeis atherosclerotic. ʻO ka hui pūʻana o nā pono kūpono, ʻo ia hoʻi kahi palapala palekana palekana o dapagliflozin e hiki ai i ka hoʻohana nui ʻana o kēia lāʻau lapaʻau no ka hoʻomaka a me ka hoʻoikaika ʻana o ka hana T2DM.

ʻO ke ʻano o ka hana ʻepekema ma ke kumumanaʻo "ʻO ke kuleana a me kahi o dapagliflozin i ka hoʻokele ʻana i ka maʻi type 2: mai ke kumu a hana"

Yu.Sh. KHALIMOV, MD, lunaolelo, P.V. AGAFONOV, ka moho o nā ʻenehana lapaʻau, V.G. KUZMICH, Ph.D. Kauila Kauka. S.M. ʻO Kirova Ministry of Defense of Russia, St. Petersburg

ʻO DAPAGLIFLOSINE I KA MANAWA o TYPE 2 DIABETES:

LELEI MAI O KA LOA

Kūkulu ʻia kahi ala hou i ka mālama ʻana o ka maʻi mellitus type type 2 (T2DM) i ka glucosuria i loaʻa i ka lāʻau a me ka hoʻohaʻahaʻa ʻana i ka paepae o ka renal o ka glucose, a me nā lāʻau lapaʻau me kahi ʻano like ʻole e pili ana i ka papa hou o nā hana hypoglycemic: type 2 sodium glucose cotransporter inhibitors (NGLT) 2). Ma kahi o ka hoʻomaikaʻi ʻana i ka mana glycemic, ua kōkua nā NGLT-2 i ka hōʻemi i ka hoʻemi ʻana o ke kaumaha o ke kino a me ke koko (BP), e hoʻonui i ka naʻau i ka insulin a hoʻomaikaʻi i ka hana p-cell. ʻO Dapagliflozin ka mea mālama i loko o ka NGLT-2, ka mea, no kona ʻano hana kūʻokoʻa o ka hana o ka insulin, ka palena liʻiliʻi o ka hypoglycemia hoʻohālikelike ʻia me nā lāʻau maʻi maʻi kūlohelohe e like me ka sulfonylurea a me ka insulin. No kēia kumu, he hiki i kā dapagliflozin ke ʻano pono me ka hui pū me nā huaʻōlelo hypoglycemic oral (PSSP). Eia kekahi, ma muli o kāna hopena natriuretic a me ka hiki ke hoʻemi i ke kaumaha o ke kino a me ke koko, ʻo dapagliflozin ka lāʻau lapaʻau e koho ai i nā mea maʻi me ka maʻi type type 2 a me nā maʻi cardiovascular o ka hopena atherosclerotic. ʻO ka hui pūʻana o nā pono kūpono, ʻo ia hoʻi kahi kōpana palekana palekana o dapagliflozin, hiki iā ia ke hoʻohana nui i kēia lāʻau lapaʻau i ka hoʻomaka a me ka hoʻoikaika ʻana o ka mālama maʻi no ka T2DM.

Nā huaʻōlelo nui: dapagliflozin, INGLT-2, ʻano type type 2 diabetes mellitus.

U.S. KHALIMOV, MD, Prof., Prof., P.V. AGAFONOV, PhD i ka lapaʻau, V.G. KUZMICH, PhD i lāʻau lapaʻau,

ʻO Kirov Military Medical Academy o ka Ministry of Defense o ka Russian Federation, St. Petersburg

ROLO MA KA LOA ʻO DAPAGLIFLOZIN I KA MANAWA ʻO ka 2 O kā TYPE DIABETES: Mai ka ʻĀwau ʻana e hana ai i ka hana.

ʻO kahi ala hou i ka mālamaʻana i ka mellitus type 2 type mellitus (T2DM) e pili ana i ka glycosuria i hoʻohui ʻia i ka lāʻau a me ka hōʻemi i ka

ka helu ʻai ʻana i ka maʻi glucose, a me nā lāʻau lapaʻau me nā ʻano hana like ʻole i loko o kahi papa hou o nā lāʻau antidiabetic.

nā mea paʻa o ka lua ʻano sodium-glucose cotransporter (GLT-2). Hoʻohui i ka hoʻomaikaʻi ʻana i ka mālama glycemic control SGCT-2 inhibitors

hōʻemi ka nui o ka momona kaumaha a me ke koko (BP), hoʻonui i ka ʻike ʻana i nā kiko i ka insulin a hoʻomaikaʻi i ka hana p-cell.

ʻO Dapagliflozin kahi mea paʻa SGCT-2 lūlū, aia ma muli o ke kaila kūʻokoʻa o ka insulin o ke ʻano e hoʻohālikelike ʻia e ka

palena liʻiliʻi o ka hypoglycemia hoʻohālikelike i nā lāʻau lapaʻau antidiabetic maʻamau, e like me ka sulfonylurea a me ka insulin. No kēia kumu, ʻo

He pono ka lāʻau lapaʻau e hiki ke hoʻohui pū me nā lawelawe ʻē aʻe hypoglycemic agents (OHGA). ʻO kēia, ma muli o kāna hopena natriuretic a

hiki ke hōʻemi i ke kaumaha o ke kino a me ke koko dapagliflozin i ka lā koho o ke koho i nā poʻe maʻi me T2DM a me ka cardiovascular

nā maʻi āpau o nā genesis atherosclerotic. ʻO ka hui pūʻana o nā pono kūpono, ʻo ia hoʻi kahi palapala palekana palekana o dapagliflozin e ʻae

ka hoʻohana nui ʻana o kēia lāʻau lapaʻau no ka hoʻomaka a me ka hoʻoikaika ʻana o ka mālama T2DM.

Huaʻōlelo: nā lāʻau lapaʻau, SGCT-2, Type 2 diabetes mellitus.

Kūkulu ʻia kahi ala hou i ka mālama ʻana o nā maʻi mellitus type type 2 (T2DM) i ka hoʻokumu ʻia ʻana o ka glucosuria i loaʻa i ka lāʻau a me ka hoʻohaʻahaʻa ʻana i ka paepae o ka renal o ka glucose, a me nā lāʻau lapaʻau me kahi ʻano like ʻole e pili ana i ka papa mana o nā māmala hypoglycemic: type 2 sodium glucose cotransporter inhibitors (InGLT -2). He mea nui ia ka hopena o INGLT-2 ke kūpaʻa glucose a lilo i hōʻemi inā emi ka pae ʻana o ka plasma ma lalo o 5 mmol / l (90 mg / dl), no laila ke pili nei kā lākou hoʻohana me ka hopena haʻahaʻa o ka hypoglycemia hoʻohālikelike i nā lāʻau lapaʻau haʻahaʻa, ʻo ka hopena e hilinaʻi nei kahi huna o ka insulin a i ʻole ka pale ʻana o ka pale ʻana i ka insulin. Ua hōʻike ʻia nā haʻawina hoʻokolohua

ʻO ka glucosuria i hoʻokumu ʻia e INGLT-2 he mea kōkua pū kekahi i ka hoʻomaikaʻi ʻana i ka mea huna o ka insulin e nā p-cells a me ka ʻike ʻana o nā ʻiʻo peripheral i ka insulin ma muli o ka hemo o ka pehu o ka pehu o ka glucose a me ka hoʻemi ʻana o ka adipose tissue papaha 6-8. Eia kekahi, ʻo nā pono o ka haukapila koʻikoʻi o INHLT-2 ka hopena natriuretic a me ka hoʻohaʻahaʻa ʻana i ka pehu a systolic a me ka diastolic, a hiki ke loaʻa i ka hopena maikaʻi i ka hoʻomohala a me ka holomua o nā maʻi cardiovascular like 8, 9.

ʻO ka mea ʻelele o ka papa hou o ka wai hoʻohiolo wai kōpī (PSSP) - type 2 sodium glucose cotransporter inhibitors - ua apono ʻia ʻo dapagliflozin no ka hoʻohana ʻana ma ʻEulopa i ka makahiki 2012, a ma Ros-

o ka Russian Federation i ʻAukake 14, 2014 1, 2. ʻO Dapagliflozin kahi mana selektif hou i kālai ʻia o NGLT-2, ka mea alakaʻi nui i komo i ke kaʻina o ka reabsorption glucose i nā pōkole renal proximal, ka mea e hoʻopiʻi ai i ka hoʻopōhula nui o ka glucose e nā keiki. ʻO kekahi mea hana nui o ka hana o dapagliflozin i ka hoʻomaikaʻi ʻana i ka hana o nā p-cell pancreatic. ʻO kēia hopena, e wehewehe ʻia e ka emi ʻana o ka huakini o ka glucose, i hōʻike ʻia ma ka noiʻi o ka hoʻohālike no ka nānā ʻana i ka homeostasis a me ka hana p-cell (HOMA-P). No ka hōʻoia i kēia hypothesis, ua hana ʻia kahi noi e Megoah A et a1., Ka mea i hōʻike ʻia he hōʻemi i ka hoʻoliʻi ʻana o ka glucose koko glucose ma muli o ka glucosuria i lalo o ka hana a dapagliflozin e kōkua i ka hoʻomaikaʻi ʻana i ka hana o nā p-ʻāpana a hoʻemi i ka hoʻōla ʻana i ka insulin i nā poʻe maʻi me ka maʻi diabetes type 2.

Ke noʻonoʻo nei i ka hana o ke koʻi o ka hana o dapagliflozin i ka wā o ka hoʻomohala ʻana i ka lāʻau, ua mālama pono ʻia ka mālama kūikawā ʻana i ka ʻōnaehana urinary. Ma ka noi a Ferrannini E et a1. ʻo ka hoʻohana ʻana o dapagliflozin no nā hebedoma 24 ʻaʻole i alakaʻi i ka loli koʻikoʻi i loko o nā ana o ka hana māka, me ka serum creatinine, koko urea nitrogen, cystatin C. Laisk MA et a1. hōʻike i ka hoʻohana ʻana o dapagliflozin i ukali pū me ka piʻi liʻiliʻi o ka nui o ka urea nitrogen urea: ma hope o he 52 mau wiki o ka maʻi i ka hui o nā poʻe maʻi e loaʻa ana i ka dapagliflozin + metformin, he hoʻonui nui loa kēia hōʻailona ma ka 0.5 ± 0.08 mmol / L i hoʻohālikelike ʻia me 0.1 ± 0. 07 mmol / l i ka hui mālama me ka glipizide a me ka metformin. Eia naʻe, ʻaʻole i ukali ʻia kēia mau loli me ka piʻi ʻana o ka pilikia o ka impalia pōpilikia a i ʻole kaulike ʻole. Pono e hōʻike ʻia ma nā mea maʻi me ka maʻi puʻuwai maʻi, hiki ke hōʻemi ʻia ka hopena o dapagliflozin ma muli o ka emi ʻana o ka nui o ka urine, a no laila ke kuhikuhi nei ka European Medical Agency Agency i ka haʻalele i kāna hoʻohana ʻana i nā mea maʻi me ka hōʻeha a i ʻole ka hopena ʻole i ka renal.

Ua hōʻike nui ʻia nā helu loiloi a me ka loiloi 31, 32 i ka loiloi ʻana i ka palekana o dapagliflozin ma ke ʻano he monotherapy a me ka ʻano o ka hui hoʻohui ʻana i nā maʻi me nā maʻi maʻi ʻoi aku ka 32. Ua hōʻike ʻia ʻo ka hapa nui loa (> 90%) o nā hopena hōʻino (NPE) i hōʻike ʻia ma ka hopena o dapagliflozin a me ke koʻikoʻi paʻakikī me ka ʻike ʻole ʻia e ka hopena o ka lāʻau. Ua hōʻike ʻia hoʻokahi a ʻoi paha ka NPE ma 61.7% o nā maʻi e lawe ana i dapagliflozin, a me 56.9% i ka hui placebo. I ka hui dapagliflozin, ʻike ʻia ka NPE e like me ka mālama ʻana i ka maʻi ma 17,3% o nā maʻi, ma ka hui plasebo, ma ka 13.3%. ʻO ka NPE maʻamau i loko o ka pūʻulu dapaglif-losin he hypoglycemia, maʻi urinary tract, vulvovaginitis / balanitis a me nā pili o ka maʻi, ka hopena, polyuria, dysuria a me ka dyslipidemia. ʻO AE mau koʻikoʻi e alakaʻi ana e hoʻokuʻu

ua nānā ʻia ka lāʻau lapaʻau ma ka like like me nā poʻe maʻi i nā dapagliflozin a me nā hui pletebo (3.7 a me 3.3%, 2.8 a me 2,5%, kahi like).

Hōʻike i kekahi mau paʻi i ka hoʻomohala ʻana o nā hihia līpika i ka ketoacidosis maʻi (DKA) me ka hoʻohana ʻana o nā mea hoʻohana o NGLT-2. No ka mea ua hoʻopaʻa ʻia nā hihia o ka hoʻomohala ketoacidosis i ka wā o ka hoʻohana ʻana o nā lāʻau lapaʻau ʻē aʻe mai ka hui o nā mea huna o NGLT-2, hiki ke manaʻo ʻia he ʻano iki kēia hopena o ka papa piha o nā lāʻau lapaʻau inā ʻaʻole i hāhai ʻia nā ʻōkuhi no ka hoʻohana ʻana i nā mea maʻi me nā kiʻekiʻe o ka insulin, ma kahi ketoacidosis e uhi ʻia e ka concomitant euglycemia. ʻOiai ʻo kēia, i ka 2015, ua hoʻololi ka US Food and Drug Administration (FDA) i nā ʻōkuhi no ka hoʻohana ʻana i nā lālā o ka pūʻulu InGLT-2 e hoʻohui i kahi mea e pili ana i ka pilikia o ka hoʻomohala ʻana i ka keto-acidosis maʻi. Ma ka makahiki 2016, ua hoʻopuka nā keʻena luna Lūkini o Johnson a me Johnson a me Astrazeneca Pharmaceutical i kahi leka hōʻike e hōʻike ana iā lākou e pono ai ka hoʻomalu kūikawā i ka hopena o ka hoʻomohala ʻana o ka DKA, ka mea kūikawā i nā poʻe maʻi me ka hoʻohaʻahaʻa i nā waiwai o nā b-cell, me ka liʻiliʻi o ka meaʻai a i ʻole ka make , he hōʻemi nui i ka pau ʻana o ka insulin, kahi nui e pono ai ka insulin (no ka laʻana, e kūʻē i ke kua o ka pathology), i ka wā o ka hōʻemi a me ka hōʻino wai.

ʻO ka hana o INGLT-2 ka hilinaʻi o ka glucose a lilo ka liʻiliʻi inā hāʻule ka pae ʻana o ka glucose glucose ma lalo o 5 mmol / l (90 mg / dl), no laila ua pili kā lākou hoʻohana ʻana me ka hopena haʻahaʻa o ka hypoglycemia hoʻohālikelike ʻia me nā lāʻau hoʻohaʻahaʻa i ka hilo, nā hopena e hilinaʻi i ka huna ʻana i ka insulin a i ʻole ke pae ʻana o ka pale ʻana o ka insulin.

Pono e hoʻomanaʻo ʻia he mau haʻawina o ka lua a me ke kolu o ka papahana o ka lāʻau lapaʻau no ka noi ʻana o dapagliflozin i hōʻike i ka hoʻonui iki ʻana o ka maʻi pā ʻana i nā maʻi ʻeha o nā kāne a me nā umauma umauma i nā wahine i hoʻohālikelike ʻia me ka pinepine o kēia mau maʻi i nā makahiki maʻamau o nā poʻe maʻi me ka maʻi maʻamau o 26, 33 ʻAʻole i koʻikoʻi nā kaʻawale o ka ʻokoʻa, ka hoʻomohala ʻana i ka maʻi pā ʻana a me ka maʻi umauma o nā maʻi i nā mea āpau i hana ʻia i loko o ka makahiki 1 a me 2 mau makahiki, ma hope iho o ka hoʻomaka ʻana o ka ʻoihana dapagliflozin ʻAe, ʻoiai ka laulā ākea o ka heterogeneity o ke kanesa, ʻoi loa ke kuhi ʻana i ka maʻi maʻi, ʻaʻole ia e ʻae iā mākou e noʻonoʻo i ka hopena o ka lāʻau lapaʻau ke kumu nui. Hōʻike ʻia nā ʻikepili mai ma mua o 20 mau haʻawina hou i hana ʻia ma mua o Nowemapa 2013 ʻaʻole i hōʻike i nāʻokoʻa i ka pinepine o nā neoplasms malignant i nā maʻi e mālama ʻia ana me dapagliflozin 9, 26. ʻOiai nā ʻōpili a nā ʻānō

ʻaʻohe hopena nui o ka hopena o ka neoplasms malignant me dapagliflozin, a ʻo ke ʻano mua o ka maʻi o ke kano, ʻo ia paha ka hopena o ka hewa ʻōnaehana ma ka ʻike ʻana i nā hopena, e nānā pololei ʻia kēia pilikia ma nā haʻawina hou o dapagliflozin 9, 26, 33. Ma ka laulā, he kōkuhi ʻoluʻolu a wānana no dapagliflozin ua hōʻoia ʻia e ka hōʻike ʻana o nā ʻano loiloi like ʻole a me nā loiloi ʻōnaehana i paʻi ʻia a hiki i kēia lā 31, 32.

Ke wehewehe nei i ka pono o dapagliflozin, pono e koʻikoʻi ka mea e hōʻiliʻili nei kahi hanana Lūkini nui loa me ka hoʻohana ʻana i kēia lāʻau lapaʻau. Loaʻa ka mālama Dapagliflozin i Lūkini i mua o 26 tausani mau mea maʻi me ka maʻi diabetes 2 ʻano. Hiki ke hoʻohana ʻia ʻo Dapagliflozin e like me ka monotherapy a me ka hui pū ʻana me nā lāʻau lapaʻau haʻahaʻa, e hui pū me ka insulin.

Ua hōʻike ʻia ka hopena o ka monotherapy dapagliflozin i loko o nā haʻawina loea he nui. No laila, ma ke aʻo ʻana o Komoroski B. et aL., Ka lawena ʻia ma mua o 14 mau lā, ma ka pau ʻana o ke hoʻopaʻa ʻana i nā poʻe maʻi me ka maʻi type 2 ua loaʻa nō ke ʻano kinikina nui e hilinaʻi i loko o glucosuria mai 36.6 g i 70.1 g i kēlā me kēia lā ke kaola o ka monotherapy me nā ʻano like ʻole o dapagliflozin. ma ka pūʻulu placebo, ʻo kēia hōʻailona he 6 g / lā wale nō.

Ma kekahi noiʻi, List JF et al., Ka mea i hoʻopili ai i nā mea maʻi 389 me ka maʻi diabetes type 2, hōʻike ʻo dapagliflozin i kona ʻano e kaohi ʻana i ka glycemia a me ke kaumaha o ke kino, he mea nui ia no kēia mahele o nā maʻi. I ka wā o ka hoʻopaʻa ʻana, loaʻa i nā mea maʻi ka dapagliflozin i loko o nā ʻano ʻelima ʻē aʻe - 2.5, 5, 10, 20 a me 50 mg, me metformin a placebo paha he 12 mau pule. Ma ke ka hopena o ka noi ʻana, kahi hōʻemi i hilinaʻi nui ʻia ma ka pae o HbA1c o 0.55-0.90% i nānā ʻia ma nā pūʻulu dapagliflozin, na 0.73% i ka hui metformin

Kuhi 1. Hoʻonui ka hilinaʻi-dosis i loko o ka urcr glucose glucose

a he 0.18% i ka hui placebo. ʻO ka hoʻokeo ʻana i ka hoʻoliʻiliʻi koko ma ka 0.88-1.70 mmol / L i ka hui dapagliflozin, e 0.99 mmol / L i ka hui metformin a ma 0.33 mmol / L i ka hui placebo. Ma kahi o kēlā mau hōʻemi e like me ke kiʻekiʻe o ka glucose koko ma hope e mālama ʻia i nā hui āpau. Loaʻa kahi kikoʻe HbA1c ma lalo o 7.0% i loaʻa i ka 40-59% o nā hihia ma nā pūʻulu dapagliflozin (e like me ka maʻi) a hoʻohālikelike ʻia me 54% o nā hihia ma ka hui metformin a me 32% i ka hui placebo.

No laila, e hoʻomaopopo pono ʻia ka hoʻohālikelike pono o ka monotherapy dapagliflozin i ka metformin, a me ka hopena glycemic maikaʻi a me ka hoʻolilo ʻana i ke kaumaha me ka dapagliflozin monotherapy, i mālama ʻia i nā haʻawina ʻoi pōkole ma hope, i hoʻomau ʻia no ka manawa lōʻihi mai 52 a 102 pule.

ʻO Dapagliflozin kahi mea mālama hoʻomalu paʻa hou o NGLT-2, ka mea alakaʻi nui i hoʻokomo ʻia i ke kaʻina hana o ka glucose reabsorption i nā polula renal proximal, e alakaʻi ana i ka hoʻopukapuka i nā glucose hou i hoʻopuka ʻia e nā keiki.

Ma kahi o ka hōʻemi pono ʻana i ka glycemia i ka wā monoter dapagliflozin, ua nānā pono ʻia kahi hōʻemi o ke kino ke hoʻohālikelike ʻia me nā metformin a me nā pūʻulu plasebo: 2.5-3.4 kg ma mua o 1.7 kg a me 1,2 kg, kela me ia. ʻO ka emi ʻana o ke kaumaha o ke kino i ka wā o ka maʻi me ka dapagliflozin i hiki ke kahakaha ma muli o kona hopena pololei - ke emi ʻana o ka reabsorption renal glucose, kahi e hiki ai i ka nalowale o kekahi helu kilocalories: ma kahi o 70 g o glucose i kēlā me kēia lā (kahi e pili ana i ka nalowale o 280 kcal / lā) 2, 16.

ʻAʻole i ʻike ʻia nā hopena maikaʻi ʻole me ka hoʻohana pū ʻana o dapagliflosin. Ua nui nā hoʻokolohua ʻelua, ʻelua makapō, nā loko o ka pletebo i nā maʻi me ka maʻi diabetes type 2 i hoʻolaʻa ʻia e nānā ai i ka hopena o dapagliflozin ma ke ʻano o ka hui hoʻohui ʻana me ka metformin a me ka insulin. No laila, ma ka hoʻopaʻaʻana o BaNeu C1 et a1. hōʻike ʻia i ka hoʻohui ʻana o dapagliflozin i loko o nā helu o ka 2,5 mg, 5 mg a me 10 mg i ka poʻe maʻi me ka mana glycemic maikaʻi ma ke kumu o ka metformin monotherapy e hōʻike ana i ka hoʻomaikaʻi ʻana i ka ʻaina HbA1c a me ka wikiwiki o ka glucose glucose i hoʻohālikelike ʻia me ka hui hoʻokele. Ma hope o 24 wiki o ka mālama ʻana, aia ka nui a me ka mea nui loa, ka hopena o ka hōʻemi ʻana i ka hopena o ka maʻi o ka HbA1c mai ka 0.67% (95% CI: 0.53-0.81, p = 0.0002) i ka hui o 2.5 mg o dapagliflozin i 0, 84% (95% CI: 0.700.98, p ʻaʻole hiki ke loaʻa kahi mea āu e makemake ai? E hoʻāʻo e lawelawe i kahi palapala koho pepa.

Dapagliflozin 10 mg + metfomin i ka wiki 102

(n = 132, ka helu kumu mua o ID1 me 7.95%)

(95 °% CI, -0.97, -0.60%, n = 57)

0 7 14 21 28 35 42 49 56 63 70 77 84 91 98

No laila, i ka wā o ka mālama holoʻokoʻa me ka dapa-glyphlozin, ʻaʻohe lilo o ka hana pono o ka lāʻau, e hoʻokaʻawale ana i kēia lāʻau lapaʻau mai nā iwi ʻē aʻe o ka huka haʻahaʻa a me ka hana o ka hana o ka insulin i ka hana.

Ma hope o 24 mau pule o ka hoʻopaʻa ʻana, ʻo 33% o nā mea maʻi e loaʻa ana he 5 mg o dapagliflozin + metformin a me 40.6% o nā maʻi e loaʻa ana he 10 mg o dapagliflozin + metformin ua loaʻa i kahi o ka pae HLA1c ma kahi o 7%, ʻoiai i ka hui placebo + metformin kēia hōʻailona ʻo ia wale nō 25,9%. Ma ka like like, ʻo ka hopena maikaʻi o ka hui pū ʻana me ka dapa-glyphlozine ma ke koʻikoʻi o ke kino ua hoʻopaʻa ʻia ma hope o 24 wiki o ka mālama ʻana. ʻO ka emi ʻana o ke kaupaona kino o £ 5% i mālama ʻia ma ka 18.1-22.1% o nā mea maʻi i nā pūʻulu hui dapagliflozin + metformin a me nā awelika o 2.2-2.9 kg, ʻoiai i ka hui plato pleto + metformin, hōʻemi ka paona kino wale nō e ka 0 9 kg. Ua maopopo loa he hopena koʻikoʻi o ka mālama ʻana ʻaʻole wale ka mea maoli o ka hoʻolimalima ʻana o ke kaupaona ʻana, akā ʻo ka mālama ʻana i ka hopena i loaʻa i ka manawa lōʻihi. E like me nā hopena o kēia noi ʻana

ka lawe ʻana i ka dapagliflozin i ka hui me ka metformin e alakaʻi i ka kaohi o ke kino o ke kino ma kahi o 102 mau pule.

No ka loiloi i ka hopena o ka lāʻau lapaʻau ma ke ʻano o ka momona nui i kēia noiʻi ʻana, ua loiloi mākou i ka ʻōpū hope: i hōʻemi ʻia ka nui o ka pale ʻana i loko o nā ʻōpū e pili ana i nā maʻi me ka maʻi type 2 i ka dapagliflozin a me nā hui metformin

Kiʻi 3. ʻO ke kaumaha a me ka noho ʻana

no 102 pule

ka nui o ka 1.7-2.5 cm i hoʻohālikelike ʻia i 1,3 cm i ka hui placebo me ka hui pū me nā metformin, kahi e hōʻike ai i ka hoʻemi o ka momona o ka ʻōpū.

Loaʻa ka mālama Dapagliflozin i Lūkini i mua o 26 tausani mau mea maʻi me ka maʻi diabetes type 2. Hiki ke hoʻohana ʻia ʻo Dapagliflozin e like me ka monotherapy a me ka hui pū ʻana me nā lāʻau lapaʻau haʻahaʻa, e hui pū me ka insulin

Ua hōʻike ʻia kekahi hopena maikaʻi ma ka paona o ke kino a me ka paona hope i ka BoLinder J et aL. Aʻo, kahi o nā mea maʻi me T2DM e loaʻa ana i ka metformin monotherapy i hana pilikino i ʻelua mau pūʻulu: dapagliflozin 10 mg a me ka placebo. Ma hope o 24 mau hebedoma o ka ʻoihana dapagliflozin i hui pū me ka metformin, ua nānā ʻia kahi hōʻemi o ke kino o 2,08 kg (95% CI: 1.31-2.84, p i loaʻa ʻole i ka mea āu e pono ai.

Ua ʻike ʻia ʻo ka hopena o dapagliflozin i ka wā i hoʻohana pū ʻia me ka dipeptidyl peptidase-4 inhibitor sitagliptin a me kahi glodepiride derivative sulfonylurea.

I ka poʻe maʻi me ka kontrol glycemic maikaʻi aʻo ka lawe ʻana i ka sitagliptin 100 mg / lā ± metformin £ 1,500 mg / lā, e hoʻohui ana i ka 10 mg o dapagliflozin i ka hoʻoponopono koʻikoʻi i kōkua i nā pōmaikaʻi hou: ma hope o 24 mau pule o ka maʻi, ua hōʻemi ʻia ka nui o ka pae HbA1c (0.5 % ke hoʻohālikelike ʻia ka 0,0% i ka hui placebo, pi ʻImi ʻole e ʻike i kāu mea e pono ai?

Haʻi pule

0.20% (95% CI, 0.05, 0.36)

Kāhea -0.30 °% (95% CI, -0.51, -0.09)

-0.10% (95% CI, -0.25, 0.05)

Wahi a ka nui o nā ʻike, ua pili pū ka hypoglycemia koʻikoʻi me nā pilikia cardiovascular a me ka make o ka make ma nā maʻi me nā maʻi maʻi type 2. Eia kekahi, he hopena maikaʻi ka hypoglycemia i ka hoʻokō ʻana i nā pahuhopu o ka hoʻohaʻahaʻa i ke kō, e hoʻākāka ʻia e nā hōʻemi o ka mālama ʻana o ka mea maʻi i ka hoʻōla ʻana, ʻo ka pilikia ka ʻike ʻana i nā ʻōlelo a ke kauka a kauka a he maʻamau ka mea e pale ai i ka manawa kūpono o ka mālama ʻana e nā kauka, ʻo ia hoʻi i ka wā e pili ana i ka insulin. No kēia kumu, ʻo ka uluʻana o ka hypoglycemia ke kumu palekana palekana mua i loiloi ʻia i kēia hoʻokolokolo lōʻihi. Ua hōʻike ʻia ma ka pūʻulu dapagliflozin, ʻo ka nui o nā mea maʻi me ka hoʻomohala ʻana i hoʻokahi manawa o ka hypoglycemia i ka manawa o ka hana i ko 4 mau makahiki he 10 mau minuke ma mua o ka hui glipizide: 5.4 kūlike 51.5%, kēlā. Eia kekahi, i ka hoʻohana ʻana o dapagliflozin, ʻaʻohe mau hihia o ka hypoglycemia koʻikoʻi.

Ke noʻonoʻo nei i ka mea e kōkua ai ka T2DM i ka holomua o ka papa o nā maʻi cardiovascular, palekana cardiovascular a me ka hopena i nā pānaʻi o ke ʻano o ke ʻano o ka pūnaehana cardiovascular ma ke ʻano o ka hana nui i ka hoʻomohala ʻana i nā lāʻau lapaʻau hou. ʻO ka hoʻonui mai o ka diuresis i ka wā o ka maʻi me dapagliflozin i hui pū me ka hoʻohaʻemi ʻana o ke kaupaona i ke kino e alakaʻi i kahi hōʻemi akā e hoʻokūkū mau i ke koko. ʻO ka loiloi o ka dinamika o nā mākau hele koko i loko o nā mea maʻi i kēia noiʻi hōʻike i loko o ka hui dapagliflozin i hōʻemi ʻia ka pae o ka pae systolic blood pressure (SBP) i ʻike ʻia me ka mea mua, a ua hoʻomau ʻia ka hopena i nā pae a pau o ka nānā ʻana: ma hope o 1 makahiki, ka pae

ʻO GARDEN kahi haʻahaʻa e 4.10 mm RT. Art., Ma hope o 2 mau makahiki - e 3.0 mm RT. Art., A ma hope o 4 makahiki - e 3.69 mm RT. Art., ʻOiai i ka hui glipizide i loko o ke aʻo ʻana, ʻaʻole i loli maoli ka pae o ke kahe koko. I ka hopena o ka makahiki 4 o ka nānā ʻana, ka ʻokoʻa ma waena o nā hui i ka dinamics o ka pae o ka SBP ma ka -3.67 mm RT. ʻAniā. (95% CI: -5.92 iā -1.41).

Ua hōʻoia ʻia ka hopena hypotensive o dapagliflozin i loko o kahi hoʻopaʻa aʻo ʻana i 24 pule e Nauck M.A. et aL., e hōʻike ana, ma muli o ke ʻano, i ka wā e hoʻohana ai iā dapagliflozin, ua hiki i nā mea maʻi ke loaʻa i ka pae o ke kaila o ke koko i ka 29.5-37.5% o nā hihia i hoʻohālikelike ʻia

Kiʻi 5. Ka hopena haʻahaʻa o ka hypoglycemia me ka hoʻokele

ua hoʻohālikelike ʻo dapagliflozin me ka sulfonylurea glipizide i kahi makahiki 4 makahiki

60 50 40 30 20 10 0

I ka loaʻa ʻana o ka hypoglycemia ma loko o ke aʻo holoʻokoʻa (208 mau pule)

(p ʻAʻole hiki iaʻu ke loaʻa i kāu mea e pono ai? E ho'āʻo i ka lawelawe koho palapala.

I loko o kēia mau noiʻi, loiloi nā hopena o ka dapa-glyphlozine ma kahi waiʻo 2.5-10.0 mg i hoʻohālikelike ʻia me ka kaohi ʻana me ka monotherapy, a pēlā pū me ka PSSP ʻē aʻe. Ua hōʻike ʻia nā hopena o ka nānā ʻana o nā mea maʻi 9,339, kahi o 5,936 nā mea maʻi i loaʻa

Kiʻi 6. ʻO ka hopena o dapagliflozin i ka hopena o nā hōʻemi cardiovascular e like me ka meta-analysis e Sonesson C. et al.

Nā kaina ʻauhau ʻole i hoʻolālā ʻia e ka maʻi myocardial revascularization no ka paʻa ʻana o ka puʻuwai

ʻO RR - ka pilikia pili, HF - ka puʻuwai naʻau

inā he dapagliflozin a me 3,403 he wahi placebo a i ʻole he lāʻau lapaʻau hoʻohālikelike. Ua loiloi ka meta-analect i ka hopena o ka hoʻomohala ʻana i nā hoʻopiʻi cardiovascular (ʻo ka mea i hoʻohui ʻia ka hopena mua ka make mai ka CVD, myocardial infarction, stroke a me ka hoʻolaʻa ʻana no ka angina hiki ʻole), ka loaʻa ʻana o ka hopena i hoʻolālā ʻole ʻia no ka myocardial revascularization a me ka nui o nā hale hoʻokipa ma muli o ka nele o ka naʻau. Hōʻike nā hualoaʻa o kahi meta-analysis i ka palekana o dapagliflozin, me ka poʻe maʻi me CVD (ʻoiai ʻole ka helu o nā hanana cardiovascular ma ka mōʻaukala) a ma kahi hui o nā maʻi kahiko me CVD. Mea kūpono (ma o ke alaloa o nā hakahaka ma muli o ka palaualole) a i ʻole ka hopena neʻe o dapagliflozin i hoʻomaopopo ʻia no nā ʻāpana helu āpau.

Hōʻike nā hualoaʻa o kahi meta-analysis i ka palekana o dapagliflozin, me ka poʻe maʻi me ka CVD (ʻoiai ʻole ka helu o ka mōʻaukala o nā hanana cardiovascular) a ma ka hui o nā poʻe maʻi me CVD

I ka makahiki 2012, ua hoʻokumu ʻia ka nui loa o nā hoʻopaʻa mau ʻana o nā inhibitors o NGLT-2: kahi hoʻokolohua hoʻokolohua multicenter e hoʻokolokolo ai i ka hopena o ka lapaʻau dapagliflozin e pili ana i ka hopena o nā hoʻopiʻi cardiovascular ma nā mea maʻi me ka maʻi maʻamau 2, DECLARE-TIMI58. Ma muli o ka hōʻike ʻana o ka DECLARE ma mua o 17,000 mau mea maʻi me ka maʻi diabetes type 2 nona ke 40 mau makahiki a keu aku, me nā mea he nui ko ka CVD a i ʻole nā kumu pākuʻi he nui. No laila, ʻo ka loiloi loiloi i ka hopena o dapagliflozin i ka hopena o ka hoʻomohala ʻana o nā hoʻopiʻi cardiovascular ma ka nui o ka poʻe maʻi hoʻomanawanui. Hoʻoholo ʻia nā hopena noiʻi DECLARE i 2019.

No laila, ʻae nā NGLT-2 i kahi papa hou o nā lāʻau lapaʻau haʻahaʻa me ka ʻokoʻa kūʻokoʻa o ka hana a kūʻokoʻa i ka insulin. Hoʻokahi wale ka hopena o kēia mau lāʻau i ka glucose glucose a me ka hana hana ʻole. Ma kahi o ka hoʻomaikaʻi ʻana i ka mana glycemic, nā inhibitor NGLT-2, ma muli o nā hopena pololei a kūlohelohe, e hāʻawi i ka hōʻemi ʻana i ka momona o ke kino a me ke koko, hoʻonui i ka naʻau i ka insulin a hoʻomaikaʻi i ka hana p-cell. ʻO Dapagliflozin kahi mea mālama pilikino o NGLT-2, ka hiʻohiʻona e ka palena liʻiliʻi o ka hypoglycemia i hoʻohālikelike ʻia me kahi kīʻaha maʻamau -

0,704 (0,364-1,359) 0,567 (0,339-0,947) 0,999 (0,536-1,864) 0,870 (0,475-1,593) 0,729 (0,479-1,067) 0,361 (0,156-0,838)

0,785 (0,365-1,689) 0,578 (0,301-1,107) 1,009 (0,491-2,074) 0,883 (0,442-1,767) 0,795 (0,512-1,233) 0,371 (0,155-0,889)

1,018 (0,369-2,811) 0,767 (0,295-1,994) 0,806 (0,317-2,050) 0,706 (0,263-1,895) 0,952 (0,493-1,836) 0,389 (0,103-1,470)

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1 papa i kēlā me kēia lā, ʻaʻohe titration a me nā waina, me ka manaʻo ʻole e kākau

nā lāʻau lapaʻau no ka mālama ʻana i ka maʻi maʻi, e like me ka sulfonylurea a me ka insulin. No kēia kumu, pono paha e kuhi ʻia ʻo dapagliflozin i kekahi mau mea lapaʻau ʻē aʻe i nā maʻi mea i loaʻa ʻole i kā lākou mau pahuhopu me ka metformin monotherapy. Ma muli o kona hiki ke hoʻoikaika maikaʻi i nā kumu alakaʻi o ka pilikia cardiovascular, me ka hopena natriuretic

ʻo dapagliflozin ka lāʻau lapaʻau e koho ai i nā mea maʻi me ka maʻi type 2 a me nā maʻi cardiovascular o ka hopena atherosclerotic. ʻO ka hui pū ʻana o kēia mau pono, me ka maikaʻi o ka pānaʻi palekana maikaʻi o dapagliflozin, e hiki ai i ka lāʻau lapaʻau ke hoʻohana nui i ka hoʻomaka a me ka hoʻomohala ʻana i ka mālama nei no T2DM. f

1. Ke Kahuli Kūloko ma ʻEulopa. Komite no nā lāʻau lapaʻau no ka hoʻohana kanaka. Hoike hōʻike. Forxiga (dapagliflozin). Kepakemapa 18, 2012. http://www.ema.europa.eu/docs/en_ GB / document_library / EPAR _-_ Public_assessment_ report / human / 002322 / WC500136024.pdf.

2. Nā ʻōkuʻi no ka hoʻohana ʻana i ka lāʻau lapaʻau ʻo Forsig, pili ʻia i nā loli 1-4. Palapala palapala Hoʻohui ʻApela 002596 o 08.21.14

3. AZ-Bridge. Kauka lāʻau lapaʻau no nā poʻe loea. Pūnaewele uila, Kepakemapa 12, 2016. URL: http://www.az-most.ru/ news / forxiga-new-horizon.html.

4. Dedov I.I., Shestakova M.V. Kākau 2 type mellitus: mai ka ʻenehana i ka hana. M .: Kaukaʻi Pūnaewele Hoʻonaʻauao Hale Hōʻikeʻike ʻAmelika, 2016: 291-301.

5. Scheen AJ. Pharmacodynamics, kūpono a me ka palekana o ka sodium-glucose co-transporter type 2 (SGLT2) inhibitors no ka mālama ʻana i ka maʻi mellitus type 2. Nā lāʻau lapaʻau, 2015, 75: 33-59.

6. ʻO Merovci A, Mari A, Solis C, Xiong J, Daniele G, Chavez A. Dapagliflozin hoʻemi i ka hoʻokaʻawale i ka glucose o ka glucose a hoʻomaikaʻi i ka hana hana cell cell. J Clin Endocrinol Metab,, 2015, 100 (5): 1927-32.

7. Scheen AJ, ka hopena Paquot N. Metabola o nā mea hoʻomehana SGLT-2 ma mua o ka hoʻonui ʻia o ka glucosuria: kahi loiloi o nā hōʻike hōʻike. Hoʻopili i ka maʻi maʻamau. 2014, 40: S4-11.

8. Nauck MA. Hoʻomou hou i nā hoʻomohala me nā SGLT2 inhibitors i ka hoʻokele o ka maʻi type 2. Kaukaʻina Des Devel Ther,, 2014, 8: 1335-80.

9. Fioretto et al. Ka maikaʻi a me ka palekana o dapagliflozin, he sodium glucose cotransporter 2 (SGLT2) inhibitor, ma ka maʻi mellitus. Diabetol Cardiovasc, 2015, 14: 142.

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