Beyond Oral Agents & Insulin: Beyond Oral Agents & Insulin: New Frontiers in the Management of New Frontiers in the Management of Diabetes and Cardiometabolic RiskDiabetes and Cardiometabolic Risk

A Primary Care InitiativeA Primary Care Initiative

Learning ObjectivesLearning Objectives

• Describe the role of incretin physiology in Describe the role of incretin physiology in diabetes and diabetes treatmentdiabetes and diabetes treatment

• Explain the mechanism of action of the Explain the mechanism of action of the incretin mimetics incretin mimetics

• Identify the role of glucose metabolism in Identify the role of glucose metabolism in addressing cardiometabolic riskaddressing cardiometabolic risk

• Integrate incretin mimetics in clinical practiceIntegrate incretin mimetics in clinical practice

Therapy for Type 2 Diabetes (T2DM):Therapy for Type 2 Diabetes (T2DM):Sites of ActionSites of Action

PancreasPancreas

LiverLiver MusclesMuscles

GutGut

Thiazolidinedione Thiazolidinedione Exogenous insulinExogenous insulin

BiguanidesBiguanidesIncretin mimeticsIncretin mimeticsAmylin analoguesAmylin analogues

HyperglycemiaHyperglycemia

Incretin mimeticsIncretin mimetics

Alpha glucosidase Alpha glucosidase inhibitorsinhibitorsIncretin mimeticsIncretin mimeticsAmylin analoguesAmylin analogues

SulfonylureaSulfonylureaSecretagoguesSecretagogues

Clearly, we have many choices in Clearly, we have many choices in

diabetes management, and yet...diabetes management, and yet...

master rheumatology series

Master Rheumatology SeriesMaster Rheumatology SeriesInflammatory Cytokines in Rheumatoid Inflammatory Cytokines in Rheumatoid

Arthritis: Disease Modulators and Arthritis: Disease Modulators and Therapeutic TargetsTherapeutic Targets

Development of New Drugs Development of New Drugs Directed at Inflammatory CytokinesDirected at Inflammatory Cytokines

Dr White, MDDr White, MD

master rheumatology series

master rheumatology series

Certolizumab: ACR ResponsesCertolizumab: ACR ResponsesAfter 8 Weeks of Treatment After 8 Weeks of Treatment

Pat

ien

ts (

%)

16.7

0

25

12.5

75

12.5

75

50

0

20

40

60

80

ACR20 ACR50

Placebo

Certolizumab 1 mg/kg

Certolizumab 5 mg/kg

Certolizumab 20 mg/kg

Managing the Strains of Influenza:Managing the Strains of Influenza:An Effective Model for An Effective Model for

Prevention and TreatmentPrevention and Treatment

Structure of the Influenza VirusStructure of the Influenza Virus

InfluenzaInfluenzaVirusVirus

AnatomyAnatomy

NeuraminidaseNeuraminidase

HemagglutininHemagglutininCapsidCapsid

ViralViralRNARNAM2M2

ProteinProtein

LipidLipidEnvelopeEnvelope

Transmission and ReproductionTransmission and Reproductionof Influenza Virusof Influenza Virus

Plasma membranePlasma membrane

EndoplasmicEndoplasmicreticulumreticulum

CoatedCoatedpitpit

CellCellreceptorreceptor

ExtracellularExtracellular

Stage 1:Stage 1:AttachmentAttachment

Stage 2:Stage 2:EntryEntry

Stage 3:Stage 3:UncoatingUncoating

CytoplasmCytoplasm

BuddingBudding

GolgiGolgiapparatusapparatus

mRNAmRNA

(HA, NA)(HA, NA)

Synthesis ofSynthesis ofenvelope proteinsenvelope proteins

NucleusNucleus

1997-19981997-1998Influenza-like IllnessesInfluenza-like Illnesses

1998-19991998-1999Influenza-like IllnessesInfluenza-like Illnesses

VaccineVaccine(n=576)(n=576)

PlaceboPlacebo(n=554)(n=554)

PP VaccineVaccine(n=582)(n=582)

PlaceboPlacebo(n=596)(n=596)

PP

IllnessesIllnesses 0.280.28 0.240.24 NSNS 0.140.14 0.220.22 <0.001<0.001

Days IllDays Ill 2.382.38 1.731.73 0.010.01 1.021.02 1.541.54 <0001<0001

Physician VisitsPhysician Visits 0.110.11 0.090.09 NSNS 0.050.05 0.090.09 <0.001<0.001

Lost WorkdaysLost Workdays 0.290.29 0.200.20 0.0470.047 0.080.08 0.120.12 0.0020.002

Patients With Patients With Lost WorkdaysLost Workdays

0.080.08 0.090.09 NSNS 0.080.08 0.120.12 <0.001<0.001

Effectiveness of VaccinationEffectiveness of Vaccinationin Healthy Working Adultsin Healthy Working Adults