HK1202458A1 - Glucokinase activator compositions for the treatment of diabetes - Google Patents

Glucokinase activator compositions for the treatment of diabetes Download PDF

Info

Publication number
HK1202458A1
HK1202458A1 HK15103235.2A HK15103235A HK1202458A1 HK 1202458 A1 HK1202458 A1 HK 1202458A1 HK 15103235 A HK15103235 A HK 15103235A HK 1202458 A1 HK1202458 A1 HK 1202458A1
Authority
HK
Hong Kong
Prior art keywords
pharmaceutically acceptable
acceptable salt
glucokinase activator
diabetes
insulin
Prior art date
Application number
HK15103235.2A
Other languages
English (en)
Chinese (zh)
Inventor
.瓦爾卡爾斯洛佩茲
M.C.瓦尔卡尔斯洛佩兹
.方
T.方
Original Assignee
Vtv治疗有限责任公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Vtv治疗有限责任公司 filed Critical Vtv治疗有限责任公司
Publication of HK1202458A1 publication Critical patent/HK1202458A1/xx

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/26—Glucagons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Zoology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Cardiology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Emergency Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Rheumatology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Vascular Medicine (AREA)
  • Dermatology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
HK15103235.2A 2012-05-17 2013-05-15 Glucokinase activator compositions for the treatment of diabetes HK1202458A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201261648110P 2012-05-17 2012-05-17
US61/648,110 2012-05-17
PCT/US2013/041076 WO2013173417A2 (en) 2012-05-17 2013-05-15 Glucokinase activator compositions for the treatment of diabetes

Publications (1)

Publication Number Publication Date
HK1202458A1 true HK1202458A1 (en) 2015-10-02

Family

ID=48576527

Family Applications (1)

Application Number Title Priority Date Filing Date
HK15103235.2A HK1202458A1 (en) 2012-05-17 2013-05-15 Glucokinase activator compositions for the treatment of diabetes

Country Status (16)

Country Link
US (3) US10004782B2 (cg-RX-API-DMAC7.html)
EP (1) EP2849776B1 (cg-RX-API-DMAC7.html)
JP (1) JP6234443B2 (cg-RX-API-DMAC7.html)
KR (2) KR20150013838A (cg-RX-API-DMAC7.html)
CN (2) CN118453592A (cg-RX-API-DMAC7.html)
AU (2) AU2013262895A1 (cg-RX-API-DMAC7.html)
BR (1) BR112014028622A2 (cg-RX-API-DMAC7.html)
CA (1) CA2872021C (cg-RX-API-DMAC7.html)
EA (1) EA201492109A1 (cg-RX-API-DMAC7.html)
ES (1) ES2878001T3 (cg-RX-API-DMAC7.html)
HK (1) HK1202458A1 (cg-RX-API-DMAC7.html)
IL (1) IL235484A0 (cg-RX-API-DMAC7.html)
IN (1) IN2014DN09554A (cg-RX-API-DMAC7.html)
MX (1) MX360304B (cg-RX-API-DMAC7.html)
SG (2) SG10201609644UA (cg-RX-API-DMAC7.html)
WO (1) WO2013173417A2 (cg-RX-API-DMAC7.html)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT2576524T (pt) 2010-05-26 2017-11-17 Vtv Therapeutics Llc Resumo
IN2014DN09554A (cg-RX-API-DMAC7.html) * 2012-05-17 2015-07-17 Transtech Pharma Llc
KR102408480B1 (ko) 2018-05-30 2022-06-10 이삼구 당뇨질환의 치료용 조성물
BR112020024269A2 (pt) * 2018-05-31 2021-02-23 Hua Medicine (Shanghai) Ltd. combinação farmacêutica, composição e formulação de combinação contendo ativador de glucoquinase e ativador de receptor ppar e métodos de preparação e usos dos mesmos
CA3093025A1 (en) 2018-06-12 2019-12-19 Vtv Therapeutics Llc Therapeutic uses of glucokinase activators in combination with insulin or insulin analogs
AU2020426356A1 (en) * 2020-01-31 2022-08-25 Hua Medicine (Shanghai) Ltd. Treating treatment-resistant diabetes with glucokinase activator
US11872221B2 (en) 2020-01-31 2024-01-16 Hua Medicine (Shanghai) Ltd. Treating untreated or treatment-resistant diabetes with glucokinase activator
US12391658B2 (en) 2020-02-18 2025-08-19 Vtv Therapeutics Llc Sulfoxide and sulfone glucokinase activators and methods of use thereof
WO2021243646A1 (en) * 2020-06-04 2021-12-09 Hua Medicine (Shanghai) Ltd. Glucokinase activator for treating diabetes with hepatic impairment
CA3185831A1 (en) * 2020-06-04 2021-12-09 Hua Medicine (Shanghai) Ltd. Glucokinase activator for treating diabetes with renal impairment
US11857536B2 (en) 2020-06-04 2024-01-02 Hua Medicine (Shanghai) Ltd. Glucokinase activator for treating diabetes with renal impairment
US12479808B2 (en) 2020-06-08 2025-11-25 Vtv Therapeutics Llc Salts or co-crystals of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid and uses thereof
CA3181665A1 (en) * 2020-06-08 2021-12-16 Jing TENG Crystalline forms of {2-[3-cyclohexyl-3-(trans-4-propoxy- cyclohexyl)-ureido]-thiazol-5-ylsulfanyl} -acetic acid and and uses thereof
CN115350268B (zh) * 2022-08-24 2025-02-11 深圳青澜生物技术有限公司 一种用于治疗糖尿病的制剂、微针及其制备工艺

Family Cites Families (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AT323195B (de) 1973-03-16 1975-06-25 Hurka Wilhelm Verfahren zur herstellung neuer salze von biguaniden
FR2243684B1 (cg-RX-API-DMAC7.html) 1973-09-19 1977-01-28 Semb
US5145684A (en) 1991-01-25 1992-09-08 Sterling Drug Inc. Surface modified drug nanoparticles
US5552160A (en) 1991-01-25 1996-09-03 Nanosystems L.L.C. Surface modified NSAID nanoparticles
US6794412B1 (en) * 1999-03-11 2004-09-21 Bristol-Myers Squibb Pharma Company Treatment of thrombosis by combined use of a factor Xa inhibitor and aspirin
SI1133312T1 (sl) * 1999-06-21 2008-02-29 Lilly Co Eli Uporaba tiazolidindionov v kombinaciji z glukagonu podobnim peptidom-1 in njegovimi agonisti za zdravljenje sladkorne bolezni, neodvisne od inzulina
US6294546B1 (en) * 1999-08-30 2001-09-25 The Broad Of Trustees Of The Leland Stanford Junior University Uses of diterpenoid triepoxides as an anti-proliferative agent
US6608038B2 (en) * 2000-03-15 2003-08-19 Novartis Ag Methods and compositions for treatment of diabetes and related conditions via gene therapy
CA2744893A1 (en) 2002-06-27 2004-01-08 Novo Nordisk A/S Aryl carbonyl derivatives as glucokinase activators
WO2004076420A1 (ja) 2003-02-26 2004-09-10 Banyu Pharmaceutical Co., Ltd. ヘテロアリールカルバモイルベンゼン誘導体
JP4386035B2 (ja) 2003-07-14 2009-12-16 ソニー株式会社 情報提供システム、放送局特定サーバ、関連情報提供サーバ、コンテンツ配信サーバ、記録媒体販売サーバ及び情報提供方法
WO2005023766A1 (en) 2003-09-11 2005-03-17 Biocon Limited Salt of atorvastatin with metformin
CN1910166B (zh) * 2004-01-06 2012-01-04 诺和诺德公司 杂芳基脲及其作为葡糖激酶活化剂的用途
BRPI0506662B8 (pt) * 2004-01-06 2021-05-25 Novo Nordisk As compostos ativadores de glucoquinase
EP1758611A2 (en) * 2004-06-17 2007-03-07 Novo Nordisk A/S Use of liver-selective glucokinase activators
WO2006110809A2 (en) 2005-04-12 2006-10-19 Elan Pharma International, Limited Nanoparticulate lipase inhibitor formulations
US20100028439A1 (en) 2005-05-23 2010-02-04 Elan Pharma International Limited Nanoparticulate stabilized anti-hypertensive compositions
CN101258137A (zh) * 2005-07-08 2008-09-03 诺沃-诺迪斯克有限公司 双环烷基脲葡糖激酶活化剂
JP2009500378A (ja) 2005-07-08 2009-01-08 ノボ・ノルデイスク・エー/エス グルコキナーゼ活性化剤としてのジシクロアルキルカルバモイル尿素
JP2009500377A (ja) 2005-07-08 2009-01-08 ノボ・ノルデイスク・エー/エス ジシクロアルキルウレア型グルコキナーゼ活性化剤
JP4960355B2 (ja) 2005-07-14 2012-06-27 ノボ・ノルデイスク・エー/エス ウレア型グルコキナーゼ活性化剤
JP5419706B2 (ja) 2006-12-20 2014-02-19 タケダ カリフォルニア インコーポレイテッド グルコキナーゼアクチベーター
JP2010515701A (ja) 2007-01-09 2010-05-13 ノボ・ノルデイスク・エー/エス ウレアグルコキナーゼアクチベーター
JP5513492B2 (ja) 2008-05-16 2014-06-04 タケダ カリフォルニア インコーポレイテッド グルコキナーゼ活性剤
EP2305737A4 (en) 2008-07-22 2015-03-04 Kureha Corp PROCESS FOR PRODUCING POLYARYLENE SULFIDE HAVING REDUCED HALOGEN TERMINAL GROUP CONTENT
WO2010107610A1 (en) * 2009-03-17 2010-09-23 Merck Sharp & Dohme Corp. Method for treatment of diabetes and related conditions with combination therapy and compositions containing such compounds
AR076317A1 (es) 2009-04-16 2011-06-01 Taisho Pharmaceutical Co Ltd Composiciones farmaceuticas que comprenden un compuesto de 1-tio-d-glucitol.
KR101190957B1 (ko) 2009-08-25 2012-10-15 한올바이오파마주식회사 메트포르민 카페익산염, 그의 제조방법, 그를 포함하는 약학 조성물 및 그를 포함하는 복합제제
PT2576524T (pt) 2010-05-26 2017-11-17 Vtv Therapeutics Llc Resumo
EP2392575A1 (en) * 2010-06-04 2011-12-07 LEK Pharmaceuticals d.d. A novel synthetic approach to ß-aminobutyryl substituted compounds
IN2014DN09554A (cg-RX-API-DMAC7.html) 2012-05-17 2015-07-17 Transtech Pharma Llc
HK1213197A1 (zh) 2013-03-04 2016-06-30 Vtv治疗有限责任公司 包括葡糖激酶活化劑的固體組合物及其製備和使用方法
CA2903433A1 (en) 2013-03-04 2014-09-12 Vtv Therapeutics Llc Stable glucokinase activator compositions

Also Published As

Publication number Publication date
JP2015517525A (ja) 2015-06-22
AU2013262895A1 (en) 2014-11-13
BR112014028622A2 (pt) 2017-06-27
US10980861B2 (en) 2021-04-20
US10588943B2 (en) 2020-03-17
KR102371364B1 (ko) 2022-03-07
JP6234443B2 (ja) 2017-11-22
EP2849776A2 (en) 2015-03-25
MX360304B (es) 2018-10-29
IL235484A0 (en) 2014-12-31
EA201492109A1 (ru) 2015-07-30
US20140066372A1 (en) 2014-03-06
ES2878001T3 (es) 2021-11-18
US20180311314A1 (en) 2018-11-01
CN104349790A (zh) 2015-02-11
KR20150013838A (ko) 2015-02-05
US20200138909A1 (en) 2020-05-07
WO2013173417A2 (en) 2013-11-21
CA2872021C (en) 2022-08-16
SG11201406987UA (en) 2014-12-30
KR20210027547A (ko) 2021-03-10
CA2872021A1 (en) 2013-11-21
AU2017203835B2 (en) 2018-11-22
IN2014DN09554A (cg-RX-API-DMAC7.html) 2015-07-17
WO2013173417A3 (en) 2014-02-20
SG10201609644UA (en) 2017-01-27
CN118453592A (zh) 2024-08-09
US10004782B2 (en) 2018-06-26
AU2017203835A1 (en) 2017-06-22
MX2014013105A (es) 2015-04-08
EP2849776B1 (en) 2021-04-21

Similar Documents

Publication Publication Date Title
US10980861B2 (en) Glucokinase activator compositions for the treatment of diabetes
EP1741445B1 (en) Combinations comprising dipeptidylpeptidase-IV inhibitors and antidiabetic agents
JP5077786B2 (ja) 併用医薬
JP5611275B2 (ja) 真性糖尿病の治療のためのロフルミラスト
CN102307577A (zh) 包含sglt2抑制剂、dpp-iv抑制剂和任选的另一种抗糖尿病药的药物组合物及其用途
KR20090047546A (ko) 당뇨병을 위한 조합 치료
TW201406374A (zh) 用於治療代謝性疾病之醫藥組合
JP7005050B2 (ja) 亜鉛塩、シクロ-ヒスプロおよび抗糖尿薬物を有効成分として含有する糖尿病の予防または治療用薬学的組成物
TWI519297B (zh) 使用雙醋瑞因之糖尿病輔助療法
AU2020426356A1 (en) Treating treatment-resistant diabetes with glucokinase activator
HK1165292A (en) Pharmaceutical compositions
HK1102424B (en) Combinations comprising dipeptidylpeptidase-iv inhibitors and antidiabetic agents
HK1108359B (en) Combinations comprising dipeptidylpeptidase-iv inhibitors and antidiabetic agents
TW201247204A (en) Vasoprotective and cardioprotective antidiabetic therapy
HK1137345A (en) Combination treatment for diabetes mellitus