Drugs in Clinical Development for Type 2Diabetes MellitusSummary and Table

Type 2 diabetesmellitus is a complex and progressive endocrine

and metabolic disorder that is characterized by multiple defects in

insulin production and insulin action in muscle, adipose and liver

tissue, and is estimated to affect over 170millionpeopleworldwide.

While dietary and lifestyle interventions can maintain gly-

caemic control in some patients, eventually most patients will

require pharmacological treatment.However,many patients still

do not achieve goals for glycaemic control in clinical practice

because of worsening X-cell function, incomplete adherence

to treatment (often because of adverse treatment effects such

as weight gain and hypoglycaemia, or complexity of regimens)

and reluctance of many physicians to intensify treatment. Fur-

thermore, pharmacological agents with different mechanisms of

action are required because of the variable and progressive

pathophysiological changes associated with type 2 diabetes.

The longer established strategies to treat type 2 diabetes in-

clude increasing endogenous insulin production with sulfonyl-

ureas and meglitinides, reducing hepatic glucose production

through biguanides and limiting postprandial glucose absorp-

tionwitha-glucosidase inhibitors, aswell as the use of exogenousinsulin. However, the need for additional therapeutic ap-

proaches, combined with adverse effects associated with some

of these treatments, have led to the development of newer

agents, including thiazolidinediones, incretin-based therapies

(dipeptidyl peptidase-IV [DPP-IV] inhibitors and glucagon-like

peptide-1 [GLP-1] agonists), short- and long-acting insulin ana-

logues and sodium-glucose transporter-2 (SGLT2) inhibitors.

GLP-1 agonists, such as liraglutide and exenatide, improve

prandial insulin secretion, reduce excess glucagon production and

promote satiety. A long-acting release formulation (i.e. for once-

weekly injections) of exenatide was approved in 2011 and the

majority of other GLP-1 agonists in development are also long-

acting (either once-daily or once-weekly formulations). Some or-

ally administered formulations are also in early development.

While duration of action has been the primary focus of de-

velopment for GLP-1 agonists, DPP-IV inhibitors were devel-

oped through efforts to find orally administered compounds

that enhance the endogenous incretin effect.Anumber ofDPP-IV

inhibitors are currently licensed for use, and various fixed com-

binations (with either metformin or simvastatin) are also now

available in some countries. However, whether incretin-based

treatments can prevent disease progression is still unclear.

Insulin-sensitizing thiazolidinediones, including pioglita-

zone and rosiglitazone, were introduced as the first in a class of

peroxisome proliferator-activated receptor (PPAR) agonists

and gained worldwide use (with or without other antidiabetic

drugs). They show similar efficacy to metformin and sulfonyl-

ureas at reducing HbA1c and improve glycaemic control when

added to conventional treatments. However, rosiglitazone, a

full PPARg agonist, was withdrawn from use in some markets

in 2010 and 2011 because of concerns over cardiovascular risk,

but remains available in the US subject to restrictions. Other

PPAR agonists in development, with more favourable adverse

effect profiles, include partial PPARg agonists, the dual ago-

nists (or glitazars), which stimulate both PPARa and g recep-

tors, and pan agonists, which act on a, g and d PPAR receptors.

Unlike most diabetes treatments, SGLT2 inhibitors regulate

glucose levels through increased renal glucose elimination. Be-

cause they reduce blood glucose independently of insulin, they are

suitable for combining with other glucose-lowering agents.

SGLT2 inhibitors are advanced in clinical development and have

also shown promise for other conditions such as obesity because

they appear to promoteweight loss.However, regulatory approval

of dapagliflozin in the US has been delayed because of concerns

over a potential increase in the risk of bladder and breast cancer.

There are numerous novel treatments in development for the

treatment of type 2diabetes, including insulin-releasing glucokinase

activators, recombinant adiponectin derivatives and fatty acid syn-

thase inhibitors (see table I). In addition, some treatments offer the

possibility of once-weekly dosing, whichmay have beneficial effects

on patient satisfaction, compliance and quality of life. Combina-

tions of new therapies will target different aspects of the multifac-

torial nature of type 2 diabetes. The number of new drugs available

for the management of type 2 diabetes, together with the large

number of new entities at various stages of development, highlights

the continuing importance of type 2 diabetes in public health.

ADIS PROFILE SUMMARYPharm Med 2012; 26 (1): 27-43

1178-2595/12/0001-0027/$49.95/0

ª 2012 Adis Data Information BV. All rights reserved.

Table

I.Adisprofile

table

fortype2diabetesmellitusa

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

Preregistration

Dapagliflozin(BMS512148)

Bristol-Myers

Squibb

SGLT2inhibitors

PO

Inducesglucose

excretion;reducesplasm

agluco

se

levels;reducesbodyw

eightprevents

development

oftype2diabetes;preservesb-cellmass;im

proves

pancreaticisletm

orphologyinarodentm

odeloftype

2diabetes

EU,USA

Insulindegludec(N

N1250,

SIBA,soluble

insulin

basal

analogue)

NovoNordisk

ODCstimulants

Phosp

hokinasestimulants

Protein

tyrosinekinase

stimulants

SC

Hasamore

stable

glucose

-loweringeffectthan

insulin

glargine;bioequivalencebetweenU100and

U200form

ulations

EU,USA

Insulindegludec/in

sulin

aspart(D

egludecPlus,IDegAsp,

insulin

aspart/NN1250,NN5401,

SIAC,soluble

insulin

analogue

combination)

NovoNordisk

ODCstimulants

Phosp

hokinasestimulants

Protein

tyrosinekinase

stimulants

SC

EU,USA

Insulininhalation(Afrezza,

Technosphere

Insulin)

MannKindCorporation

ODCstimulants

Phosp

hokinasestimulants

Protein

tyrosinekinase

stimulants

Inhalation

Antiglycaemiceffect;displayssim

ilaronseteffects

comparedwithIV

insulin

USA

Metform

in(chewable

metform

in)

BostonTherapeutics

Glucosemodulators

PO

USA

Teneligliptin(M

P513)

MitsubishiP

harm

a

Corporation

CD26antigeninhibito

rsPO

Inhibitshypertiglyceridaemia

andhyperglycaemia

inanim

alm

odels;inhibitsplasmaDPP-IVactivity;

increasesplasmaGLP-1;reduceshigh-fatdiet-

inducedweightgain

andvisceralfatmass

Japan

PhaseIII

Albiglutide(716155,

albumin/G

LP-1,albumin/

glucagon-likepeptid

e-1

fusion

protein,GSK716155,Syncria)

HumanGenome

Science

s

GLP-1

stimulants

SC

Reducesfastingplasmagluco

seandmean24h

gluco

sein

patients

withtype2diabetes;decreases

bloodglucose

levelsfollowingoralg

luco

se

challengein

ananim

alstudy;decreasesglycaemic

excursionandstimulatesinsulin

secretion

Asia,Australia,EU,

Israel,LatinAmerica,

South

Africa,USA

Aleglitazar(R

1439,RG1439)

Roche

PPARaagonists

PPARgagonists

PO

ActsasaselectivePPARgandPPARareceptor

agonistin

vitro;displaysmore

potentantidiabetic

effectscomparedwithrosiglitazoneinmouseandrat

models;reducesplasmalipid

levels;im

proves

insulin

sensitivityin

insulin-resistantmonkeys

Australia,Canada,

EU,USA

Continuednextpage

28 Adis Profile Summary

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

Anagliptin(C

WP-0403,

SK-0403)

KyowaHakko

SanwaKagaku

Kenkyusho

CD26antigeninhibito

rsPO

Dose-dependently

improvesplasmagluco

seand

insulin

levelsduringtheoralglucose

tolerancetestin

diabeticratmodel

Japan

Balaglitazone(D

RF2593)

DrReddy’sLaboratories

PPARgagonists

PO

Dose-dependently

reducesplasm

agluco

se,

triglyce

ridesandfreefattyacidslevelsinob/obmice;

lessereffectonredbloodcellcountcomparedwith

eitherrosiglitazoneorpioglitazone

Denmark

Canagliflozin(JNJ28431754,

TA-7284)

TanabeSeiyaku

SGLT2inhibitors

PO

Significantlyincreasesurineglucose

excretion;

lowers

fedandfastingbloodglucose

levelsand

HbA1c,

andincreasesplasm

ainsulin

levelsin

preclinicalstudies;reducesbodyweightand

decreasesfoodefficiencyin

anim

alm

odels

Australia,Canada,

China,EU,India,

Japan,LatinAmerica,

Malaysia,Philippines,

South

Africa,South

Korea,USA

Canagliflozin/m

etform

in

extended-release

Depomed

Jansse

nPharm

aceutica

AMPKstimulants

Gluconeogenesisinhibitors

Glucosemodulators

SGLT2inhibitors

PO

EU,USA

Dapagliflozin/m

etform

in

(BMS-512418/m

etform

in,

dapagliflozin/extended-

releasemetform

in,

dapagliflozin/m

etform

inFDC)

Bristol-Myers

Squibb

Glucosemodulators

SGLT2inhibitors

PO

USA

Dulaglutide(G

LP-1

Fc,LY

2189265)

EliLilly

GLP-1

stimulants

IM,IV,SC

Asia,Australia,

Canada,E

urope,L

atin

America,PuertoRico,

South

Africa,USA

Empagliflozin

(BI10773)

BoehringerIngelheim

SGLT2inhibitors

PO

Increasesurinary

glucose

excretionandim

prove

s

glycaemiccontrolinrats

andmice;higherpotency

andmore

selectivityforinhibitingSGLT2compared

withremogliflozin

invitro

Asia,Canada,

Europe,Latin

America,S

outh

Africa,

USA

Empagliflozin/linagliptin

(BI10773/BI1356)

BoehringerIngelheim

CD26antigeninhibito

rs

SGLT2inhibitors

PO

Denmark,Estonia

Gemigliptin(LC150444)

LG

LifeSciences

CD26antigeninhibito

rsPO

Maintains>8

0%

inhibitionofplasm

aCD26-antigen

orDPP-IVactivityfor>2

4hin

health

ymale

volunteers;m

aintainsglycaemiccontrolinHFD/STZ

diabeticmice

India,South

Korea

HKB0701/SLM

0807

(CJ-30001,CJ-30002,

HKB-0701/SLM-0807)

CJCheiljedang

Corporation

Glucosemodulators

PO

South

Korea

Continuednextpage

Drugs in Clinical Development for Type 2 Diabetes Mellitus 29

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

Insulinoral(843362,GW

843362,hexylInsulin

M2,hexyl

insulin

monoconjugate

2,HIM

2,

IN105,NIN

058)

NobexCorporation

ODCstimulants

Phosp

hokinasestimulants

Protein

tyrosinekinase

stimulants

PO

Increasesplasm

ainsulin

levels;dosedependently

decreasespostprandialg

lucose

levelsin

alinear

manner

India

Ipragliflozin

(ASP-1941)

AstellasPharm

a

KotobukiS

eiyaku

SGLT2inhibitors

PO

Japan

Linagliptin/pioglitazone

BoehringerIngelheim

CD26antigeninhibito

rs

PPARgagonists

PO

Estonia,Germ

any,

Latvia,Spain,UK,

USA

Lixisenatide(AVE-0010,

Lyxumia,ZP10)

ZealandPharm

aGLP-1

receptoragonists

SC

Improvesglycaemiccontrolinpatients

withtype2

diabetesinadequatelycontrolledwithmetform

in;

dose-dependentlylowers

plasmagluco

selevels,

potentia

tesinsulin

secretion,reducespostprandial

gluca

gonlevels;dose-dependentlyim

provespost-

mealg

lucose

levelsandreducedgluca

gonlevels;

restoredinsulin

releaseandacce

leratedglucose

dispositionfollowinganIVG

inpatients

withtype2

diabetes;cardioprotectiveagainstmyocardial

ischaemia

reperfusioninjury

inrathearts

Asia,Australia,

Canada,Egypt,

Europe,Israel,Latin

America,Morocco,

South

Africa,USA

Lobeglitazone(C

KD501,

lobeglitazonesulfate)

ChongKunDang

PPARaagonists

PPARgagonists

PO

South

Korea

LY2963016

EliLilly

ODCstimulants

Phosp

hokinasestimulants

Protein

tyrosinekinase

stimulants

SC

Brazil,EU,Japan,

Mexico,PuertoRico,

Russia,South

Korea,

Taiwan,USA

Sitagliptin/pioglitazone

(MK-0431C)

Merck&

Co

CD26antigeninhibito

rs

PPARgagonists

PO

USA

TAK875

Takeda

FFAR1protein

stimulants

PO

Enhancesinsulin

secretionandim

prove

sgluco

se

tolerance;modulatesinsulin

secretio

nonlyat

eleva

tedglucose

levels;doesnotalterglucagon

secretion;combinatio

ntreatm

entwithmetform

in

additivelydecreasesgluco

seAUC,glycosylated

haemoglobin,andincreasesfastingplasm

ainsulin

EU,Japan,Latin

America,USA

Tofogliflozin

(CSG452,R7201,

RG

7201)

ChugaiP

harm

aceutica

lSGLT2inhibitors

PO

Japan

Trelagliptin(SYR472)

Takeda

TakedaSanDiego

CD26antigeninhibito

rsPO

Japan

Continuednextpage

30 Adis Profile Summary

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

PhaseII//III

Canakinumab(ACZ885,

antibodyA,Ilaris)

Novartis

IL-1binhibito

rsSC

Norm

alizesbiomarkerS100A12levelsin

patients

withcryopyrinasso

ciatedperiodicfever;significant

andsustainedreductionsinmarkers

ofinflammatio

n

Argentina,EU,India,

Japan,Peru,South

Africa,Turkey,USA

Metform

in(D

DMET-01,

DMMET-01,metform

in

glycinate)

LaboratoriosSilanes

Gluconeogenesisinhibitors

PO

Mexico

PhaseII

AC201

TWiP

harm

aceuticals

IL-1binhibito

rsPO

Taiwan,USA

AMG

222(ALS2-0426,

ALS20426)

Alantos

Pharm

aceutica

ls

CD26antigeninhibito

rsPO

USA

AR9281

Arete

Therapeutics

Epoxidehydrolase

inhibitors

PO

Dose-dependently

inhibitsbloodsoluble

epoxide

hydrolaseactivity;lowers

both

systolic

anddiastolic

bloodpressure

for24hin

spontaneously

hypertensiverats

USA

ATL844

PGxHealth

AdenosineA2Breceptor

antagonists

PO

USA

BGP15

N-G

eneResearch

Laboratories

HSP70stimulants

JNKMAPKinhibitors

PO

Inhibitsinsulin

resistance;reducesbodyw

eightgain

associatedwithadministrationofatypical

antipsychoticdrugs;cardioprotectiveactivityinpost-

ischaemichearts;chemoprotectiveactivityin

vitro

andin

vivo;regulatesmitochondrialfunctionthough

NO

production

Hungary,USA

BMS741672

Bristol-Myers

Squibb

CCR2receptorantagonists

PO

Russia

BMS770767

Bristol-Myers

Squibb

11b-HSD1inhibito

rsPO

Australia,Canada,

South

Korea,USA

BMS823778

Bristol-Myers

Squibb

Undefin

edmech

anism

PO

Australia,Canada,

USA

Cetilistat(ATL962,Cametor)

Alizyme

Lipaseinhibito

rsPO

Europe,USA

Chiglitazar(C

S038)

ChipscreenBiosciences

PPARaagonists

PPARdagonists

PPARgagonists

PO

Improvesim

pairedinsulin

andgluco

setolerance,

inhibitsalaninegluco

neogenesis,lowers

hepatic

glycogenlevels,andreducesplasm

atriglyceride,

totalcholesterol,non-esterifiedfattyacidsandLDL

levelsin

obese

rats

China

CJC1134(C

JC1134PC,

PC-D

AC:exendin-4)

ConjuChem

Biotechnologies

GLP-1

stimulants

SC

Reducesbloodglucose

andHbA1clevelsinpatients

withtype2diabetes;displaysantidiabeticactivityin

cellularassa

ysandvariousanim

alm

odelsof

diabetes

Canada,USA

Continuednextpage

Drugs in Clinical Development for Type 2 Diabetes Mellitus 31

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

Colestilan(cholebine,

colestim

ide,MCI-196)

MitsubishiC

hemical

MitsubishiP

harm

a

Corporation

Bile

acid

bindingprotein

modulators

Undefin

edmech

anism

PO

Cholesterol-loweringeffects;markedreductionin

bile

acid

concentrationin

theportalvein

bloodand

chyromicronin

thelymph;decreasesserum

phosp

horuslevels

Japan

DA1229

Dong-A

Pharm

aceutical

CD26antigeninhibito

rsPO

South

Korea

DM

199(D

M99)

DiaMedica

Immunosuppressants

Undefin

edmech

anism

PO

Reducesfastingbloodglucose

levelsin

aratmodel

oftype1diabetes;showsactivityagainst

autoim

munedisorders;increasesb-cellform

atio

n;

restorespeakplasmainsulin

levelsto

nearnorm

al

levels;im

provesbloodglucose

clearancein

anoral

gluco

setolerancetest;im

prove

sinsulin

sensitivityin

ananim

alm

odelo

ftype2diabetes

EU

DM

71

DiaMedica

Antioxidants

Muscarinicreceptor

agonists

PO

Canada

Enclomifene(androxal,

enclomid,enclomiphenecitrate,

testosteronetherapy,trans-

clomiphene)

ReprosTherapeutics

Estrogenreceptor

antagonists

Testosteroneagonists

PO

USA

EX1000

NovoNordisk

ODCstimulants

Phosp

hokinasestimulants

Tyrosineaminotransferase

stimulants

SC

Brazil,India,South

Africa,UnitedArab

Emirates

Exenatidelong-acting

(HM-11260C,LAPS-exendin

4analogue)

HanmiP

harm

aceutica

lGLP-1

stimulants

SC

Netherlands

Exenatidesuspension

(exenatid

eoncemonthly

suspension)

Amylin

Pharm

aceuticals

GLP-1

stimulants

SC

USA

Gevokizumab(XMA005.2,

XMA0052,XOMA052Mab,

XOMA-052)

XOMA

IL-1binhibito

rsSC

Reducestheform

ationofatherosclerotic

lesionsin

theaortain

mice;im

provesbloodglucose

parameters

andb-secretionfunction;reduceshigh

sensitivityC-reactiveprotein

anderythrocyte

sedim

entatio

nrate

inpatients

withtype2diabetes;

prevents

adversecardiacremodellingin

mouse

model;reducesIL-6

productio

nin

vitro;signifcant

beneficialeffectsofcombinatio

nwitheitherexendin-

4orsitagliptin

onfastinginsulin,stimulatedinsulin

secretion,b-cellproliferationandb-cellmassin

a

Mexico,USA

Continuednextpage

32 Adis Profile Summary

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

mousemodelo

ftype2diabetes;decreasesC-

reactiveprotein

levelsandHbA1clevelsin

humans

withtype2diabetes

GFT505

Genfit

PPARaagonists

PPARdagonists

PO

Doesnotincreasehomocysteineorcreatinine

levels,reducesmarkers

ofinflammation,im

proves

lipidmetabolism;significantly

reducesplasmalevels

ofALTandGGT;reducesfastingplasmaglucose

andinsulin

levelsin

pre-diabeticpatients;im

proves

insulin

actio

nontheadiposetissuesfollowingameal

test;inhibitsdiet-inducedincreasesin

proinflammatory

andprofibroticgenesandprevents

steatosisin

amousemodelo

fNAFLD/NASH

Bosnia

Herzegovina,

France,Latvia,

Macedonia,Moldova,

Romania,Serbia

GSK1292263

GlaxoSmithKline

Bombesin

receptor

agonists

PO

USA

GSK1362885(1362885)

GlaxoSmithKline

Glyco

genphosp

horylase

inhibitors

PO

Decreasesserum

gluco

selevela

ndincreases

hepaticglycogenlevelsin

anim

als

USA

GSK256073(256073)

GlaxoSmithKline

Gprotein-coupledreceptor

agonists

GPR109Areceptor

agonists

Nicotinicreceptoragonists

PO

USA

HDVinsulin(H

DV-B,HDV-I,

oralH

DV-I)

Diasome

Pharm

aceutica

lsLLC

ODCstimulants

Phosp

hokinasestimulants

Tyrosineaminotransferase

stimulants

PO

Stim

ulateshepaticactivityandenhanceshepatic

gluco

seuptake;reducespostprandialg

lycaemia

USA

HE3286(Triolex)

Hollis-Eden

Pharm

aceutica

ls

MAPKmodulators

NF-kBinhibitors

PO

Increasessurvivala

ndreducesinflammationin

mousemodelsofinflammation,sepsisandmultiple

sclerosis;im

provesinsulin

metabolism

and

suppresse

sprogressionofhyperglycaemia

in

anim

alm

odelsoftype2diabetes

USA

Hyaluronidase/in

sulin(aspart-

PH20,insulin-PH20,lispro-

PH20,recombinanthuman

hyaluronidase/in

sulin,

rHuPH20/in

sulin,ultrafast

insulin)

HalozymeTherapeutics

Hyaluronidasestimulants

ODCstimulants

Protein

tyrosinekinase

stimulants

SC

Reducespostprandialg

luco

secomparedwith

insulin

alonein

patients

withdiabetes;

insulin

+rH

uPH20producessim

ilarto

insulin

lispro

pharm

acodynamics,

while

insulin

lispro

plus

rHuPH20hassuperiorto

insulin

lispro

pharm

acodynamics;

acce

leratesinsulin

actionin

health

ysubjects;faster-in

andfaster-out

gluco

dynamicprofile

thaninsulin

aspartalone

USA Continuednextpage

Drugs in Clinical Development for Type 2 Diabetes Mellitus 33

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

Imeglimin

MerckSerono

AMPKstimulants

Glucosemodulators

PO

France,Hungary,

Latvia,Slovakia

INCB13739(INCB013739)

Incyte

Corporation

11b-HSD1inhibito

rsPO

Inhibits11b-HSD1in

both

adiposetissueandliver;

improve

sfastingbloodglucose

,reducesLDL,total

cholesterola

ndtriglycerides;doesnotincrease

testosteroneorsuppressandrogenictargetproteins

PuertoRico,USA

Indeglitazar(PLX-204,

PPM-204)

Plexxikon

PPARaagonists

PPARdagonists

PPARgagonists

PO

Decreasesfastinginsulin

levelsandtriglyceride

levelsin

obese

insulin-resistantrhesusmonkeys

USA

INGAPPeptide(Exsu

lin)

Eastern

Virginia

MedicalS

chool

McGillUniversity

Transcriptionfactor

stimulants

SC

IncreasesstimulatedC-peptid

ein

patients

withtype

1diabetes

USA

Insulinintranasal(insulin

nasalspray-MDRNA)

Nastech

Pharm

aceutica

l

Company

ODCstimulants

Phosp

hokinasestimulants

Tyrosineaminotransferase

stimulants

Intranasal

USA

Insulinoral(C

apsulin)

Diabetology

ODCstimulants

Phosp

hokinasestimulants

Tyrosineaminotransferase

stimulants

PO

UK

Insulinoral(O

RMD0801)

Oramed

Pharm

aceutica

ls

ODCstimulants

Phosp

hokinasestimulants

Tyrosineaminotransferase

stimulants

PO

India,Israel,South

Africa

Insulintransderm

al(TPM

02/in

sulin,TPM/in

sulin)

Phosphagenics

ODCstimulants

Phosp

hokinasestimulants

Protein

tyrosinekinase

stimulants

Transderm

al

Antihyperglycaemiceffectin

anim

als;lowers

blood

gluco

sein

anim

alstudies

Australia

INT131(AMG

131,INT131

besylate,T0903131,T131)

Amgen

PPARgagonists

PPARgmodulators

PO

Improvesfastinggluco

selevelsandinsulin

resistance;increasesadiponectin

Mexico,USA

ITCA650(Exendin-4

DUROS)

Intarcia

Therapeutics

GLP-1

stimulants

SC

ReduceslevelsofHbA1candFPG

USA

JNJ41443532

Johnson&

Johnson

Pharm

aceutica

l

Research&

Development

Undefin

edmech

anism

PO

USA

JTT130

JapanTobacco

Microsomaltriglyce

ride

transferprotein

inhibitors

PO

CzechRepublic,

Hungary,Netherlands,

Russia,USA

Continuednextpage

34 Adis Profile Summary

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

K111(BM

170744)

Kowa

PPARaagonists

PO

Stim

ulatesgluco

seconsumptionandim

proveslipid

profile

inanim

als

Europe,Japan,USA

KRP104

ActivXBiosciences

KyorinPharm

aceutical

CD26antigeninhibito

rsPO

Japan,USA

LCQ

908(LCQ908A)

Novartis

DiacylglycerolO

acyltransferaseinhibitors

Undefin

edmech

anism

PO

Argentina,Canada,

Italy,Poland,Puerto

Rico,USA

Luseogliflozin

(TS071)

TaishoPharm

aceutica

lSGLT2inhibitors

PO

Long-term

treatm

entwithluseogliflozin

improve

s

hyperglycaemia

andprevents

thelossofb-cells

in

diabeticmice

Japan

LX4211

Lexicon

Pharm

aceutica

ls

SGLT1inhibitors

SGLT2inhibitors

PO

IncreasesGLP-1

andPYYlevels;reducesfasting

andpostprandialg

lucose

levels

USA

LY2409021

EliLilly

Glucagonreceptor

antagonists

PO

Lim

itsgluca

gon-inducedincreasesin

bloodgluco

se

EU,PuertoRico,USA

LY2523199(11sz-H

SD1

inhibitor)

EliLilly

11b-HSD1inhibito

rsUnknown

USA

LY2605541

EliLilly

ODCstimulants

Phosp

hokinasestimulants

Protein

tyrosinekinase

stimulants

SC

Australia,Europe,

PuertoRico,USA

MB07803

MetabasisTherapeutics

Fructosebisphosphatase

inhibitors

Gluconeogenesisinhibitors

PO

Orally

bioavailable;efficientlyconvertedto

MB

07729;displaysglucose

-loweringeffects;may

reducepotentia

lforacid-basedisturbance

USA

MBX2982(SAR260093)

Metabolex

GPR119protein

agonists

PO

Improvesglucose

tolerancethroughmultiple

mech

anism

(e.g.reducesgluco

seexcursion)in

volunteers

andmenwithim

pairedfastinggluco

se

Georgia,India,USA

Melogliptin(EMD675992,

GRC8200)

Glenmark

Pharm

aceutica

lsLtd

CD26antigeninhibito

rsPO

InhibitsDPP-IVinvitro

andinvivo;e

levateslevelsof

GLP-1

andinsulin

inthepresenceofaglucose

load

inseverala

nim

alm

odels

India,South

Africa

Mesenchymalstem

cell

therapies(exvivocultu

redadult

allogenicmesenchymalstem

cells,ex-vivoculturedadult

humanmese

nchymalstem

cells,

stempeucelD

M)

Stempeutics

Osteogenesisstimulants

Tissuereplacements

Parenteral

India

Metform

incontrolledrelease

(metform

inXL)

FlamelT

echnologies

Glucosemodulators

PO

France

Continuednextpage

Drugs in Clinical Development for Type 2 Diabetes Mellitus 35

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

MK3102

Merck&

Co

Undefin

edmech

anism

PO

NewZealand,T

aiwan,

USA

MK3577

Merck&

Co

Glucagonreceptor

antagonists

PO

Europe,India,Latin

America,S

outh

Africa,

South

EastAsia,USA

MSDC0160(m

itoglitazone)

Metabolic

Solutions

DevelopmentCompany

Mitochondrialp

rotein

stimulants

PO

Stim

ulatesmitochondrialbiogenesisinvitro;induces

differentiatio

nofprogenitorcells

into

brown-likefat

cells

invitro

USA

MSDC0602

Metabolic

Solutions

DevelopmentCompany

Mitochondrialp

rotein

stimulants

PO

USA

Obeticholicacid

(6ECDCA,

DSP1747,INT747)

Intercept

Pharm

aceutica

ls

Farnesoid

X-activated

receptoragonists

PO

ImprovesHDLandtriglyce

ridelevels;restoreslevels

ofNKTcells

andincreaseslevelsofmonocyte-

derivedsuppresso

rcells

indb/dbobese

mice;

increasesperipheralg

lucose

uptake,enhances

gluco

se-stimulatedinsulin

secretion,induceslipid

storageinto

adipocytesandinhibitslipid

synthesis

USA

P1736(P1736-05)

PiramalL

ifeScience

sPO

Showedperipheralsensitisationinanim

alm

odelsof

insulin

resistance

Netherlands

PF4971729(PF04971729)

Pfizer

SGLT2inhibitors

PO

Lowers

bloodpressure

inspontaneously

hypertensiverats

Canada,India,

Malaysia,Mexico,

PuertoRico,Serbia,

South

Korea,Taiwan,

USA

PF4991532(PF-04991532)

Pfizer

PO

USA

Phenterm

ine/to

piramate

(phenterm

ine/controlledrelease

topiramate,Qnexa,VI0521)

VIVUS

Adrenergicreceptor

agonists

CNSstimulants

GABAreceptoragonists

Glutamate

receptor

antagonists

Neurotransmitter

stimulants

Sodium

channel

antagonists

PO

Syn

ergistically

inhibits

bingeeatingofahigh-fat

show,increaseslocomotoractivityandcalories

burnedin

feedingmodelsin

rats

USA

PN2034

WellstatTherapeutics

Corporation

PPARgagonists

PO

Norm

alizesserum

glucose

andinsulin

levels,

decreasesserum

triglyce

rides,attenuatesweight

gain,andamelioratessteatohepatitisin

mice

USA

PSN821

Prosidion

GPR119protein

agonists

PO

PSN821lowers

gluco

seandinducesbodyweight

reductionsin

rats

UK

Continuednextpage

36 Adis Profile Summary

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

Ranolazineextended-release

(CVT303,C

VT3041,K

EG1295,

RAND,Ran4,Ranexa,RS

43285,RS43285-003,RS

43285-193)

Partialfattyacid

oxidation

inhibitors

Pyruvate

dehyd

rogenase

stimulants

Sodium

channel

antagonists

PO

Cardioprotectiveandanti-anginale

ffects;increases

cardiacefficiency;

exhibitsantiarrhythmicactivity

USA

Recombinantexenatide-4

(rExenatid

e-4)

CSPCPharm

aInsulinotropin

agonists

SC

China

RG

4929(R

4929,RO5093151)

Roche

11b-HSD1inhibito

rsPO

EU,USA

RO

4998452

Roche

PO

Australia,Canada,

EU,HongKong,

Japan,LatinAmerica,

USA

S44497

Servier

Undefin

edmech

anism

PO

Germ

any,Spain,UK

S707106

Shionogi

PO

USA

Semaglutide(N

N9535,once-

weeklyGLP-1

analogue)

NovoNordisk

GLP-1

stimulants

SC

EU,India,Serbia,

South

Africa,

Switzerland,Turkey

SRT2104(2245840,GSK

2245840)

Sirtris

SIRT1protein

stimulants

PO

Europe

Taspoglutide(BIM

51077,BM

51077,BN51077,ITM-077,

R1583,RG

1583)

Ipsen

GLP-1

stimulants

SC

Lowers

bloodgluco

sein

anim

alm

odelsoftype2

diabetes;p

reventsdevelopmentoftype2diabetesin

rats;reducesthepostprandialresponseofintestinal

peptid

esPYYandGIP

inZDFrats

Japan

TC6987

Targacept

a7Nicotinicacetylcholine

receptormodulators

PO

USA

Teglicar(ST1326)

sigma-tauSpA

CarnitineO-

palm

itoyltransferase

inhibitors

PO

Reducesplasmaglucose

,decreases

fructosaminelevels

Italy

THR0921(C

LX-0921,EGT-

0001474,EGT001474,

THR0921)

CalyxTherapeutics

(CEASED)

PPARgagonists

PO

Reducesbloodglucose

levels;improve

slipidprofile;

anti-arthriticeffects

Canada,USA

TTP399

TransTechPharm

aGlucokinasestimulants

PO

USA

Usistapide(JNJ-16269110,

R-256918)

Johnson&

Johnson

Microsomaltriglyce

ride

transferprotein

inhibitors

PO

Inhibitsmicrosomaltriglyce

ridetransferprotein

and

apolipoproteinBsecretioninvitro;d

osedependently

inhibitspostprandialincreaseofp

lasmatriglyce

rides

indogs

Europe

Continuednextpage

Drugs in Clinical Development for Type 2 Diabetes Mellitus 37

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

VVP808

VervaPharm

aceutica

lsPO

Reducesfoodintakeandcausesmoderate

lossof

bodyw

eightin

diabeticandobesemice;reduces

PEPCKandG6Paseexpression,lowers

gluco

se

productionin

Faocells;enhancesgluco

se-lowering

effects

ofinsulin

inratmodel;decreasesgluco

se

infusionrate

inmousemodel

Australia

CCX140(C

CX140-B)

ChemoCentryx

CCR2receptorantagonists

PO

Noeffects

onplasm

aMCP-1

levelsorcirculating

monocyte

populations;

improvesmetabolic

function

andreducesinflammatory

macrophagesin

adipose

tissuein

mice;dose-dependentdecreasein

fasting

plasm

agluco

se

Australia,Czech

Republic,Germ

any,

Hungary,New

Zealand

PhaseI//II

Glucagon-likepeptide-1

oral

Emisphere

Technologies

GLP-1

stimulants

PO

Increasesinsulin

releasein

health

ysubjects

Switzerland

LIK

066

Novartis

Pharm

aceutica

ls

Corporation

Undefin

edmech

anism

Unknown

USA

PB1023(G

LP-1-ELP-120,

Glymera,PB1023)

PhaseBio

Pharm

aceutica

ls

GLP-1

receptoragonists

SC

USA

SLV337

SolvayPharm

aceuticals

Undefin

edmech

anism

PO

Bulgaria,Poland,

South

Africa

Taurocholicacid

(sodium

taurocholate,taurocholate)

Satiogen

Pharm

aceutica

ls

Gprotein-coupledreceptor

agonists

Rectal

Dose-dependentreductionoffoodintake;

associatedwithweightloss;associatedwith

increasedinsulin

secretionanddecreasedplasma

gluco

seconcentrations

Australia,UnitedArab

Emirates

TTP054

TransTechPharm

aGLP-1

receptoragonists

PO

USA

TTP814

TransTechPharm

aProtein-tyrosine-

phosp

hatase

inhibitors

PO

USA

PhaseI

ADV1002401

AdvinusTherapeutics

Merck&

Co

Undefin

edmech

anism

PO

India

AntisensePTP-1Bgene

therapy(ISIS-PTP1B,ISIS-

PTP1BRx)

IsisPharm

aceuticals

Protein

tyrosine

phosp

hatase

nonreceptor

type1antagonists

Parenteral

USA

AP1030

ActionPharm

aMelanocortin

type1

receptormodulators

Melanocortin

type4

receptormodulators

PO

Significantlyim

provesglucose

metabolism

inobese

volunteers;positiveallostericmodulatorof

melanocortintype1and4receptors;reducedfasting

gluco

se,insulin

andcholesterolinobeserats

Denmark,France

Continuednextpage

38 Adis Profile Summary

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

ARI2243

Arisaph

Pharm

aceutica

ls

CD26antigeninhibito

rsPO

Lowers

glycosylatedhaemoglobin

levelsandslows

diabetesprogressionin

ananim

alm

odelo

ftype2

diabetes

USA

ARRY403(AMG

151)

ArrayBioPharm

aGlucokinasestimulants

PO

Lowers

fastedandnonfastedbloodglucose

in

preclinicalm

odelsoftype2diabetes;potently

activateshumanglucokinase

USA

ASP4178

AstellasPharm

aUndefin

edmech

anism

PO

USA

ASP5034

AstellasPharm

aUndefin

edmech

anism

PO

USA

AVE0897

Genfit

sanofi-aventis

PPARaagonists

PPARgagonists

Unknown

Europe

AZD7687

AstraZeneca

DiacylglycerolO

acyltransferaseinhibitors

PO

UK,USA

AZD8329

AstraZeneca

11b-HSD1inhibito

rsPO

Sweden,UK

AZP01(non-acylatedghrelin,

UAG,unacylatedghrelin)

ErasmusMedical

Center

UniversityofTorino

Ghrelin

modulators

IVEnhancesearlyinsulin

responseto

meals;improves

gluco

semetabolism

andinsulin

sensitivity;inhibits

lipolysis;a

ntagonizestheeffectsofg

hrelin

oninsulin

secretionandgluco

semetabolism

France

BI135585(BI135585XX)

BoehringerIngelheim

VitaePharm

aceuticals

11b-HSD1inhibito

rsPO

Germ

any,South

Korea

BMS820132

Bristol-Myers

Squibb

Undefin

edmech

anism

PO

USA

BMS903452

Bristol-Myers

Squibb

Undefin

edmech

anism

PO

USA

BYK324677

Nycomed

Undefin

edmech

anism

PO

Germ

any

CAT1004

Catabasis

Pharm

aceutica

ls

Arachidonicacid

inhibito

rs

Cyclo-oxygenaseinhibito

rs

Inflammatio

nmediator

inhibitors

Plateletaggregation

inhibitors

PO

USA

CNTO

3649

CentocorOrthoBiotech

Undefin

edmech

anism

IV,SC

USA

DB959(D

B959Na)

BayerHealth

Care

Pharm

aceutica

ls

PPARdagonists

PPARgagonists

PO

Improvesinsulin

sensitivity,increasesHDL

cholesterol,im

prove

sHDL:LDLratio,lowers

triglyce

ridelevelsanim

alm

odelsofdyslipidaemia

USA

DC9703

Obio

Pharm

aceutica

l

Holdings

Undefin

edmech

anism

Unknown

USA Continuednextpage

Drugs in Clinical Development for Type 2 Diabetes Mellitus 39

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

DSP8658

DainipponSumitomo

Pharm

a

PPARaagonists

PPARgagonists

PO

Improvesmetabolic

abnorm

alitiesin

rodentmodels;

selectivelymodulatescofactorrecruitmentto

PPARg;

increasesexpressionofgenesrelatedto

gluco

semetabolism

butnotrelatedto

fat

accumulation

USA

EDM

05

ENovate

Biolife

Undefin

edmech

anism

Unknown

India

Empagliflozin/m

etform

in

(BI10773/m

etform

in)

BoehringerIngelheim

AMPKstimulants

Gluconeogenesisinhibitors

Glucosemodulators

SGLT2inhibitors

PO

Germ

any

Exenatideintranasal

(exenatid

enasal)

Amylin

Pharm

aceuticals

GLP-1

stimulants

Intranasal

Nearmaximalimprove

ments

inpost-prandial

gluco

se,atdosesof600-1800mg

USA

Exenatidesustainedrelease

(DA3091,long-actingexenatid

e)

Dong-A

Pharm

aceutical

GLP-1

stimulants

SC

Dose-proportionally

decreasesnonfastingblood

gluco

seandHbA1clevels,reducesfoodintakeand

bodyw

eightin

aratmodelo

ftype2diabetes

South

Korea

Exenatidesustainedrelease

(PT302)

Peptron

GLP-1

stimulants

SC

South

Korea

Exenatidetransderm

al

AlteaTherapeutics

GLP-1

stimulants

Transderm

al

USA

Glucagon-likepeptide-1

agonisttransderm

al(ViaDerm

-

GLP1agonist,ViaDor-GLP1

agonist)

TransPharm

aMedical

GLP-1

receptoragonists

Transderm

al

Israel

Glucagon-likepeptide-1

analogue[CM3(seco

nd-

generatio

nGLP-1),CM3protein,

CM3.1,CM3.1-AC100,CM31]

CellM

ed

GLP-1

stimulants

Insulinotropin

agonists

SC

Germ

any

GSK1614235(1614235,DSP-

3235,KGA3235)

KisseiP

harm

aceutical

SGLT1inhibitors

PO

Europe,USA

GSK2330672(2330672)

GlaxoSmithKline

Undefin

edmech

anism

Unknown

USA

INCB20817

Incyte

Corporation

Hydroxysteroid

dehyd

rogenaseinhibitors

PO

USA

Insulin

KingsCollegeLondon

ODCstimulants

Unknown

UK

Insulinprandialinjectable

form

ulations(BIO

D102,

BIO

D103)

Biodel

ODCstimulants

Phosp

hokinasestimulants

Protein

tyrosinekinase

stimulants

SC

USA Continuednextpage

40 Adis Profile Summary

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

Insulintransderm

al(AT-1391)

AlteaTherapeutics

ODCstimulants

Phosp

hokinasestimulants

Protein

tyrosinekinase

stimulants

Transderm

al

USA

Insulintransderm

al

Derm

isonics

ODCstimulants

Phosp

hokinasestimulants

Protein

tyrosinekinase

stimulants

Transderm

al

USA

ISIS

388626(ISIS-SGLT2Rx)

IsisPharm

aceuticals

SGLT2inhibitors

SC

Decreasespostprandialp

lasmaglucose

levelsand

glycosylatedhaemoglobinlevelsinanim

alm

odelsof

diabetes;decreasesrenalS

GLT2mRNA

expressionmouseandratmodelsofdiabetes;

decreasesrenalS

GLT2expressionin

norm

al

monkeys

Netherlands

JNJ38431055

Johnson&

Johnson

PO

USA

JTT851

JapanTobacco

FFAR1protein

stimulants

PO

Japan

KB3305(A

348441,KB003305)

Karo

Bio

Glucocorticoid

receptor

antagonists

PO

ImprovesFPG;d

ecreasespostprandialgluco

seand

glycosylatedhaemoglobin

levels,reducesfreefatty

acidsandtriglyce

ridelevelsinanim

alm

odelsoftype

2diabetes

Sweden

LIM

0705

Lim

erickBioPharm

aATP-bindingcassette

transporterstimulants

PO

Improvesglycaemiccontrolinrodentmodelsof

insulin

resistance/ty

pe2diabetes;health

y

volunteers

treatedwithLIM

compoundshowed

significantim

prove

mentin

theirability

tometabolise

gluco

se

Australia

Linagliptin/m

etform

in

(linagliptin/m

etform

inFDC)

BoehringerIngelheim

Dipeptidylp

eptid

ase

inhibitors

Glucosemodulators

PO

Canada,Germ

any

Lixisenatide/in

sulinglargine

(AVE0010/Lantus,

lixisenatide/Lantus)

sanofi-aventis

GLP-1

receptoragonists

ODCstimulants

Phosp

hokinasestimulants

Protein

tyrosinekinase

stimulants

SC

USA

LY2393910

EliLilly

PO

Germ

any

LY2608204

EliLilly

Undefin

edmech

anism

PO

Singapore,South

Africa,USA

LY2881835

EliLilly

Undefin

edmech

anism

PO

Singapore

Continuednextpage

Drugs in Clinical Development for Type 2 Diabetes Mellitus 41

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

MK0599

Merck&

Co

Glucokinasestimulants

PO

USA

MK1006

Merck&

Co

Undefin

edmech

anism

PO

Japan,USA

NN1218

NovoNordisk

Undefin

edmech

anism

SC

USA

NN1953(N

NC0123-0000-0338,

NNC-012300000338)

NovoNordisk

Undefin

edmech

anism

PO

Germ

any

NN9068(G

LP-1

andbasal

insulin

combinatio

n,IDegLira)

NovoNordisk

GLP-1

stimulants

ODCstimulants

Phosp

hokinasestimulants

Protein

tyrosinekinase

stimulants

SC

Germ

any

NN9924

Emisphere

Technologies

NovoNordisk

GLP-1

receptoragonists

PO

Germ

any,UK

NN9925

Merrion

Pharm

aceutica

ls

NovoNordisk

GLP-1

receptoragonists

IV,PO

UK

NNC01130987

NovoNordisk

GLP-1

receptoragonists

PO

UK

NP500

Unknown

Undefin

edmech

anism

PO

USA

OAP189(PF05212389,PF

5212389,WYE-155189)

Wyeth

Undefin

edmech

anism

SC

USA

Oxyntomodulin

Merck&

Co

GLP-1

receptoragonists

Glucagonreceptoragonists

IVNetherlands

PAZ320

BostonTherapeutics

Carbohydrate

metabolism

inhibitors

Hydrolaseinhibitors

PO

USA

PF3882845(PF03882845)

Pfizer

Undefin

edmech

anism

PO

Belgium

PF4620110(PF04620110)

Pfizer

DiacylglycerolO

acyltransferaseinhibitors

PO

Belgium,Singapore,

USA

PF4856883(C

ovX096,CVX

096,PF-04856883)

CovX

GLP-1

receptoragonists

SC

USA

PF4937319(PF-04937319)

Pfizer

Undefin

edmech

anism

PO

USA

PF5175157(PF05175157)

Pfizer

Undefin

edmech

anism

PO

USA Continuednextpage

42 Adis Profile Summary

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)

Table

I.Contd

Drug(keysynonyms/brand

names)

Originator

Mech

anism

ofactio

nRoute

of

administration

Pharm

acodynamics

Countryofhighest

phase

PF5190457(PF05190457)

Pfizer

Undefin

edmech

anism

PO

Belgium

PF5231023(PF05231023)

Pfizer

Undefin

edmech

anism

IVUSA

RG

7089(R

7089)

Roche

NeuropeptideY2receptor

agonists

Unknown

Europe

RG

7685(M

AR701,RO

6807952)

IndianaUniversity

Marcadia

Biotech

Gastricinhibitory

polypeptidereceptor

agonists

GLP-1

receptoragonists

SC

USA

RO

5095932

Roche

Undefin

edmech

anism

SC

USA

SAR351034(SAR3504)

sanofi-aventis

PPARdagonists

Unknown

France

SLV341

Genfit

SolvayPharm

aceuticals

Cytoplasmicandnuclear

receptormodulators

Unknown

EU

SRT2379

Sirtris

SIRT1protein

stimulants

PO

UK

SRT3025

Sirtris

SIRT1protein

stimulants

PO

UK

T218C3(T2-18C3)

XBiotech

Immunomodulators

IVSwitzerland

TM

38837

7TM

Pharm

aCB1cannabinoid

receptor

antagonists

PO

Denmark

TTP355

TransTechPharm

aGlucokinasestimulants

PO

Significantlyincreasesgluco

semetabolism

in

hepatocytesin

vitro;effects

ongluco

semetabolism

are

selectivefortheliver;norm

alizesHbA1clevelsin

anim

alm

odelsofdiabetes

USA

VRS859(exenatide-XTEN,

VRS-859)

Amunix

GLP-1

stimulants

SC

Greatersustainedglycaemiccontrolcomparedwith

exenatideorotherknownGLP-1

analoguesin

preclinicalm

odels;tolerable

inmonkeymodels

Australia,USA

ZYH2

Zydus-Cadila

PPARaagonists

PPARgagonists

Unknown

India

ZYOG1(ZYOG-1)

ZydusCadila

GLP-1

receptoragonists

PO

India

aDrugsindevelopmenta

recitedintheirhighestp

haseofd

evelopmentforthisindicationandtheninalphabeticalorder.AllthedrugsappearingintheAdisProfiletablehavebeenselected

onthebasisofinform

ationcontainedin

R&DInsight�

,aproprietary

productofAdis,aWolte

rsKluwerbusiness.

11b-HSD1=11-beta

hydroxysteroiddehydrogenasetype1;ALT=alanineaminotransferase;AMPK=AMPactivatedproteinkinase;ATP=adenosinetriphosp

hate;AUC=areaunderthe

concentration-tim

ecurve;db/db=genetically

diabetic;DPP-IV=dipeptidylpeptid

ase

IV;FFAR1=free

fatty

acid

receptor1;FPG=fasting

plasm

agluco

se;G6Pase=glucose

-6-

phosphatase;GABA=gamma-amino

butyric

acid;GIP

=glucose

-dependentinsulinotropic

peptid

e;GGT=g-glutamyltranspeptidase;GLP-1

=gluca

gon-like

peptid

e-1;HbA1c=

haemoglobin

A1c;HDL=high-densitylipoprotein;HFD/STZ=highfatdiet/s

treptozotocin;HSP=heatshockprotein;JNK=c-JUN

N-term

inalkinase;IL

=interleukin;IM

=intramuscular;

IV=intravenous;IVG=intravenousglucose

challenge;LDL=low-densitylipoprotein;MAPK=mitogen-activatedprotein

kinase;mRNA=messengerRNA;NAFLD/NASH=nonalcoholic

fattyliverdisease

/nonalcoholic

steatohepatitis;

NF-jB=nuclearfactorkappaB;NKT=naturalkillerT;NO=nitricoxide;ob/ob=genetically

obese;ODC=ornithinedecarboxylase;

PEPCK=phosphoenolpyruvate

carboxykinase;P

O=oral;PPAR=peroxisomeproliferator-activatedreceptor;PYY=peptid

eYY;S

C=subcutaneous;S

GLT=sodium-glucosetransporter;

SIRT1=sirtuin

1;ZDF=Zuckerdiabeticfatty.

Drugs in Clinical Development for Type 2 Diabetes Mellitus 43

ª 2012 Adis Data Information BV. All rights reserved. Pharm Med 2012; 26 (1)