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Timothy S. Reid, M.D.Mercy Diabetes Center
Janesville, WI
Entity Activity Financial Consideration Comments
Novo Nordisk Speaker/Consultant Speaker Fees/Honoraria
Sanofi-Aventis Speaker/Consultant Speaker Fees/Honoraria
Janssen Speaker/Consultant Speaker Fees/Honoraria
BoehringerIngelheim/Lilly
Speaker/Consultant Speaker Fees/Honoraria
Lilly Speaker/Consultant Speaker Fees/Honoraria
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Our understanding of diabetes continues to evolve, the number of tools that we have continue to grow and the environment in
which we care for our patients continues to change…..
we have to keep up.
Individualize treatment goals for patients with T2DM that reflect the degree of hyperglycemia, co-morbid conditions, disease duration and responses to therapy
Examine the importance of customizing HgBA1c goals based on individual patient characteristics
Discuss provider-related and patient-related barriers to use of insulin and GLP-1 therapies in the management of T2DM
Analyze the safety and efficacy of current and emerging therapies, including insulin and GLP-1 therapies, for achieving glycemic and HgBA1c target goals in type 2 diabetes
Identify patients who are good candidates for GLP-1 or insulin therapy according to current guidelines
Summarize
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Evolve
http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf
Evolve
https://www.dhs.wisconsin.gov/publications/p4/p43084.pdf
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http://www.cdc.gov/diabetes/statistics/slides/maps_diabetes_trends.pdf
Estimated Diabetes Costs in the United States, 2012
Total (Direct and Indirect$245 Billion
Direct Medical Costs$176 Billion
After adjusting for population age and sex differences, average medical expenditures among people with diagnosed diabetes were 2.3 times higher than people without diabetes.
Indirect Costs$69 Billion
(disability, work loss, premature death)
http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf
Cost
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Cost
Cost to Patient:• Time• Burden of Therapy• Food Cost• Family Involvement• Emotion/Stress
Cost to Family/Support:• Time• Home Modifications• Meal Quality/Timing• Changes in Activity• Emotion/Stress
Cost to Care Team:• Time• Complexity of Care• Administrative
Burdens
Standards of Medical Care in Diabetes - 2015
Patient Centeredness
Diabetes Across The Lifespan
Advocacy for Patients with Diabetes
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Individualized Care
Approach to the management of Hyperglycemia
Approach to the management of Hyperglycemia
Patient/Disease FeaturesPatient/Disease FeaturesA1c 7%A1c 7% Less
stringentLess
stringentMore stringentMore stringent
Usually Not ModifiableUsually Not Modifiable
PotentiallyModifiablePotentiallyModifiable
Risks potentially associated with hypoglycemia and other drug adverse events
Risks potentially associated with hypoglycemia and other drug adverse events
Disease DurationDisease Duration
Life ExpectancyLife Expectancy
Important ComorbiditiesImportant Comorbidities
Established Vascular ComplicationsEstablished Vascular Complications
Patient Attitude and expected treatment effortsPatient Attitude and expected treatment efforts
Resources and Support SystemResources and Support System
lowlow highhigh
Newly diagnosedNewly diagnosed long-standinglong-standing
longlong shortshort
absentabsent severeseverefew/mildfew/mild
few/mildfew/mildabsentabsent severesevere
Highly motivated.adherent, excellent self-care capacitiesHighly motivated.adherent, excellent self-care capacities
Less motivated, non-adherent, poor self care capacities
Less motivated, non-adherent, poor self care capacities
Readily availableReadily available
limitedlimited
Approach to the management of Hyperglycemia
Patient/Disease FeaturesA1c 7% Less
stringentMore stringent
Usually Not Modifiable
PotentiallyModifiable
Risks potentially associated with hypoglycemia and other drug adverse events
Disease Duration
Life Expectancy
Important Comorbidities
Established Vascular Complications
Patient Attitude and expected treatment efforts
Resources and Support System
low high
Newly diagnosed long-standing
long short
absent severefew/mild
few/mildabsent severe
Highly motivated.adherent, excellent self-care capacities
Less motivated, non-adherent, poor self care capacities
Readily available
limited
American Diabetes Association. Summary of Revisions. In Standards of Medical Care in Diabetes – 2015. Diabetes Care 2015;38(suppl.1):S37.
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Resources Life Expectancy
Hypoglycemic Tolerance
Drug:DrugInteractionsPolypharmacy
Health Literacy
Co-morbid Conditions
<7% >8%
vs.vs.Patient
Expectation of Control
Patient Less Willing to Control
Few Co-morbid
Conditions
Many Co-morbid
Conditionsvs.vs.Long Life Short Lifevs.vs.Hypoglycemia Hyperglycemiavs.vs.
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Lifestyle Modification Dietary Management Exercise Weight Loss
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Healthy eating, wt. control, increased physical activity & diabetes education
American Diabetes Association. Approaches to glycemic treatment . Sec. 7. InStandards of Medical Care in Diabetes – 2015. Diabetes Care2015;38(Suppl. 1):S41-S48.
Diabetes Self-Management Education◦ improved diabetes knowledge◦ improved self-care behavior ◦ improved clinical outcomes lower A1C lower self-reported weight improved quality of life healthy coping lower costs
American Diabetes Association. Approaches to glycemic treatment . Sec. 7. In Standards of Medical Care in Diabetes – 2015. Diabetes Care 2015;38(Suppl. 1):S20-S21.
Pharmacologic Therapy for Type 2 DM◦ Metformin is preferred if tolerated and not
contraindicated◦ Consider Insulin if symptomatic or blood sugars
high◦ Advance therapy q3 months if not at goal◦ Patient centered approach to therapy◦ T2DM is progressive. Insulin therapy will eventually
be needed in most cases
American Diabetes Association. Approaches to glycemic treatment . Sec. 7. In Standards of Medical Care in Diabetes – 2015. Diabetes Care 2015;38(Suppl. 1):S41-S48.
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Healthy eating, wt. control, increased physical activity & diabetes educationMetformin
High EfficacyLow Hypoglycemic Risk
Weight NeutralLactic Acidosis/GI intolerance
Low Cost
If A1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference – choice dependent on a variety of patient and disease specific factors).
Efficacy……………………Hypo Risk………………..Weight………………..…..Side Effects………….…..Cost…………………….…
American Diabetes Association. Approaches to glycemic treatment . Sec. 7. InStandards of Medical Care in Diabetes – 2015. Diabetes Care2015;38(Suppl. 1):S41-S48.
Healthy eating, wt. control, increased physical activity & diabetes educationMetformin
High EfficacyLow Hypoglycemic Risk
Weight NeutralLactic Acidosis/GI intolerance
Low Cost
If A1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference – choice dependent on a variety of patient and disease specific factors).
Sulfonylurea Thiazolidinedione DPP-4 Inhibitor SGLT-2 Inhibitor GLP-1 Receptor Agonist
Insulin (basal)
Efficacy……………………Hypo Risk………………..Weight………………..…..Side Effects………….…..Cost…………………….…
High….……………….Moderate risk……….gain…………….……..hypoglycemia……….Low.……………………
high………………….low Risk……………..Gain………………….Edema,CHF,Fx’s……Low…………………
Intermediate.……….Low risk.…………….neutral………………..rare……………………high……………………
Intermediate.……….Low risk………………losing…………………GU, dehydration…….high……………………
high…………….…….Low risk………………losing………………..GI………………….….high……………………
HighestHigh riskgainhypoglycemiavariable
If A1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference – choice dependent on a variety of patient and disease-specific factors).
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Efficacy…………………Hypo Risk……………..Weight……………..…..Side Effects……….…..Cost………………….…
American Diabetes Association. Approaches to glycemic treatment . Sec. 7. InStandards of Medical Care in Diabetes – 2015. Diabetes Care2015;38(Suppl. 1):S41-S48.
4/27/2015
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Healthy eating, wt. control, increased physical activity & diabetes educationMetformin
High EfficacyLow Hypoglycemic Risk
Weight NeutralLactic Acidosis/GI intolerance
Low Cost
If A1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference – choice dependent on a variety of patient and disease specific factors).
Sulfonylurea Thiazolidinedione DPP-4 Inhibitor SGLT-2 Inhibitor GLP-1 Receptor Agonist
Insulin (basal)
Efficacy……………………Hypo Risk………………..Weight………………..…..Side Effects………….…..Cost…………………….…
High….……………….Moderate risk……….gain…………….……..hypoglycemia……….Low.……………………
high………………….low Risk……………..Gain………………….Edema,CHF,Fx’s……Cost…………………
Intermediate.……….Low risk.…………….neutral………………..rare……………………high……………………
Efficacy……………….Hypo Risk…………….Weight………………..Side Effects………….Cost……………………
Intermediate.……….Low risk………………losing…………………GU, dehydration…….high……………………
high…………….…….Low risk………………losing………………..GI………………….….high……………………
HighestHigh riskgainhypoglycemiavariable
If A1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference – choice dependent on a variety of patient and disease-specific factors).
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Sulfonylurea Thiazolidinedione DPP-4 Inhibitor SGLT-2 Inhibitor GLP-1 Receptor Agonist
Insulin (basal)
TZD
DPP-4 i
GLP-1 RA
SGLT-2 i
SU
TZD
SGLT-2 i
Insulin
If A1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables; (2) on GLP- RA, add basal insuin; or (3) on optimally titrated basal insulin, add GLP-1 RA or mealtime insulin. In refractory patients,
consider adding TZD or SGLT-2i:
Insulin
SU
DPP-4 i
SGLT-2 i
GLP-1 RA
SU
TZD
InsulinDPP-4 i
SU
TZD
Insulin
TZD
DPP-4 i
GLP-1 RA
Insulin
SGLT-2 i
American Diabetes Association. Approaches to glycemic treatment . Sec. 7. InStandards of Medical Care in Diabetes – 2015. Diabetes Care2015;38(Suppl. 1):S41-S48.
Healthy eating, wt. control, increased physical activity & diabetes educationMetformin
High EfficacyLow Hypoglycemic Risk
Weight NeutralLactic Acidosis/GI intolerance
Low Cost
If A1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference – choice dependent on a variety of patient and disease specific factors).
Sulfonylurea Thiazolidinedione DPP-4 Inhibitor SGLT-2 Inhibitor GLP-1 Receptor Agonist
Insulin (basal)
Efficacy……………………Hypo Risk………………..Weight………………..…..Side Effects………….…..Cost…………………….…
High….……………….Moderate risk……….gain…………….……..hypoglycemia……….Low.……………………
high………………….low Risk……………..Gain………………….Edema,CHF,Fx’s……Cost…………………
Intermediate.……….Low risk.…………….neutral………………..rare……………………high……………………
Efficacy……………….Hypo Risk…………….Weight………………..Side Effects………….Cost……………………
Intermediate.……….Low risk………………losing…………………GU, dehydration…….high……………………
high…………….…….Low risk………………losing………………..GI………………….….high……………………
HighestHigh riskgainhypoglycemiavariable
If A1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference – choice dependent on a variety of patient and disease-specific factors).
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Sulfonylurea Thiazolidinedione DPP-4 Inhibitor SGLT-2 Inhibitor GLP-1 Receptor Agonist
Insulin (basal)
TZD
DPP-4 i
GLP-1 RA
SGLT-2 i
SU
TZD
SGLT-2 i
Insulin
If A1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables; (2) on GLP- RA, add basal insuin; or (3) on optimally titrated basal insulin, add GLP-1 RA or mealtime insulin. In refractory patients,
consider adding TZD or SGLT-2i:
Insulin
SU
DPP-4 i
SGLT-2 i
GLP-1 RA
SU
TZD
InsulinDPP-4 i
SU
TZD
Insulin
TZD
DPP-4 i
GLP-1 RA
Insulin
SGLT-2 i
Insulin (basal) + or GLP-1 RAMealtime Insulin
Metformin+
American Diabetes Association. Approaches to glycemic treatment . Sec. 7. InStandards of Medical Care in Diabetes – 2015. Diabetes Care2015;38(Suppl. 1):S41-S48.
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The Good:◦ Structured way to think about the therapy available
for glucose control The Bad: ◦ They do not adequately address patient population
with significant co-morbid conditions The Ugly:◦ They give no direction regarding when to
discontinue medication ◦ Potentially promote poly-pharmacy
With apologies to Clint Eastwood…….
9 classes of oral medication 4 classes of subcutaneous medications New classes coming…..
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HTN and Diabetes Drug Classes in the US over the past 90 Years
Num
ber
of M
edic
atio
n C
lass
es
1
2
3
4
7
6
5
8
10
9
12
11
1920’s 1950’s 1960’s 1970’s 1980’s 1990’s 2000’s 2010’s
Insulin Sulfonylureas
(Phenformin)Withdrawn
1978Biguanides
-glucosidase Inhibitors
Thiazolidinediones
Meglitinides
GLP-1 Receptor Agonists
Amylinomimetics
DPP-4 Receptor Antagonists
Bile Acid Sequestrants
Dopamine Agonists
SGLT-2 InhibitorsRenin Inhibitors
Calcium Channel Blockers
ACE Inhibitors
Angiotensin II Receptor Blockers
Peripheral -1 Blockers
-blockers
Central -2 Agonists
DiureticsAdrenergic
neuronal blockers
Vasodialators
metformin
glimepiride
glyburide pioglitazone
acarbose
miglitol
colesevelamlinagliptin
rosiglitazone
sitagliptin
saxagliptin
nateglinide
bromocriptine
Oral Antihyperglycemic Agents
repaglinide
glipizide
canagliflozin
alogliptindapagliflozin
empagliflozin
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Acarbose Miglitol Bromocriptine Colesevelam Glimepiride Glipizide Glybruide Metformin
Nateglinide Repaglinide Pioglitazone Rosiglitazone Alogliptin Linagliptin Saxagliptin Sitagliptin Canagliflozin Dapagliflozin Emapgliflozin
DeFronzo RA. Diabetes. 2009. 58 (4): 773-795.
GLP-1
GLP-1
GLP-1
GLP-1
GLP-1
InsulinInsulin
Insulin
Insulin
Insulin
Insulin
Insulin
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asdf
Class Generic Name Trade Nameα-glucosidase Inhibitor acarobose, miglitol Precose, Glyset
amylinomimetics amylin Symlin
biguanides metformin Glucophage, Riomet
Bile Acid Sequestrants colesevelam WelChol
Dopamine Agonists bromocriptine Cycloset
DPP-4i alogliptin, linagliptinsaxagliptin, sitagliptin
Nesina, TradjentaOnglyza, Januvia
GLP-1 Agonists albiglutide, dulaglutideexenatide, liraglutide
Tanzeum, Trulicity, ByettaVictoza
Glucagon glucagon Glucagon
Insulin insulin (various) Humulin, Novolin, Humalog, Novolog, Apidra, Lantus, Levemir
meglitinides nateglinide, repaglinide Starlix, Prandin
SGLT-2i canagliflozin, dapagliflozin, empagliflozin Invokana, Farxiga, Jardiance
Sulfonylureas glimepiride, glipizide glyburide Amaryl, Glucotrol, Diabeta, Micronase
Thiazolidinediones pioglitazone, rosiglitazone Actos, Avandia
Insulin Secretion
HepaticGlucose
Production
Pancreatic Glucagon Secretion
Peripheral
Glucose Uptake
GI CHO Absorption
Renal Reabsorp-tion
of Glucose
β-cell Function
-Glucosidase Inhibitor ✔
Biguanide ✔ ✔
Bromocriptine UnknownColesevelam Unknown
DPP-4 Inhibitor ✔ ✔
Improve*
Glinide✔
SGLT-2 Inhibitor ✔
SU✔ ✔
TZD✔ ✔ Improve
National Diabetes Education Program. Available at: http://www.ndep.nih.gov/media/Drug_tables_supplement.pdf Accessed August 10, 2010 . Nathan DM, et al. Diabetes Care. 2009;32:193-203. Rodbard HW, et al. Endocr Pract. 2009;15(6):540-559. Januvia [prescribing information]. Whitehouse Station, NJ: Merck & Co., Inc.; 2010. Onglyza [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Co.; 2009. Welchol [prescribing information]. Parsippany, NJ: Daiichi Sankyo Inc.; 2011.. Cycloset [prescribinginformation]. San Diego, CA: Santarus, Inc.; 2010.
* In vitro and rodent data; preliminary human data
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GLP-1 Receptor Agonists
Insulins◦ Human Regular NPH Mix
◦ Analogue Rapid Long Acting Mix
Pramlintide(Amylin analogue)
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Robust blood sugar reduction◦ A1c reductions 1.5-3.5%
Few toxicities◦ Hypersensitivities – typically related to excipients◦ Hypoglycemia – requires monitoring and management◦ Antibodies – clinical significance ?◦ Lipodystrophy◦ Edema
Few Drug:Drug Interactions◦ Most are changes in blood sugars, high or low
Delivery◦ Vial/Syringe◦ Pens◦ Pumps◦ Inhalation
Type GenericName
Brand Name Onset Peak Duration
Rapidaspart Novolog
10-30 minutes
30 min to 3 hours 3-5 hoursglulisine Apidra
lispro Humalog
Short regular various 30-60minutes
2-5 hours Up to 12 Hours
Intermediate NPH 1.5 to 4 Hours
4-12 Hours
Up to 24 Hours
Longdetemir Levemir 0.8 to 4
hoursMinimal
peakUp to 24
hoursglargine Lantus
http://www.joslin.org/info/insulin_a_to_z_a_guide_on_different_types_of_insulin.html (Accessed 3.20.2015)
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Healthy eating, wt. control, increased physical activity & diabetes educationMetformin
High EfficacyLow Hypoglycemic Risk
Weight NeutralLactic Acidosis/GI intolerance
Low Cost
If A1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference – choice dependent on a variety of patient and disease specific factors).
Sulfonylurea Thiazolidinedione DPP-4 Inhibitor SGLT-2 Inhibitor GLP-1 Receptor Agonist
Insulin (basal)
Efficacy……………………Hypo Risk………………..Weight………………..…..Side Effects………….…..Cost…………………….…
High….……………….Moderate risk……….gain…………….……..hypoglycemia……….Low.……………………
high………………….low Risk……………..Gain………………….Edema,CHF,Fx’s……Cost…………………
Intermediate.……….Low risk.…………….neutral………………..rare……………………high……………………
Efficacy……………….Hypo Risk…………….Weight………………..Side Effects………….Cost……………………
Intermediate.……….Low risk………………losing…………………GU, dehydration…….high……………………
high…………….…….Low risk………………losing………………..GI………………….….high……………………
HighestHigh riskgainhypoglycemiavariable
If A1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference – choice dependent on a variety of patient and disease-specific factors).
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Sulfonylurea Thiazolidinedione DPP-4 Inhibitor SGLT-2 Inhibitor GLP-1 Receptor Agonist
Insulin (basal)
TZD
DPP-4 i
GLP-1 RA
SGLT-2 i
SU
TZD
SGLT-2 i
Insulin
If A1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables; (2) on GLP- RA, add basal insuin; or (3) on optimally titrated basal insulin, add GLP-1 RA or mealtime insulin. In refractory patients,
consider adding TZD or SGLT-2i:
Insulin
SU
DPP-4 i
SGLT-2 i
GLP-1 RA
SU
TZD
InsulinDPP-4 i
SU
TZD
Insulin
TZD
DPP-4 i
GLP-1 RA
Insulin
SGLT-2 i
Insulin (basal) + or GLP-1 RAMealtime Insulin
Metformin+
American Diabetes Association. Approaches to glycemic treatment . Sec. 7. InStandards of Medical Care in Diabetes – 2015. Diabetes Care2015;38(Suppl. 1):S41-S48.
Healthy eating, wt. control, increased physical activity & diabetes educationMetformin
High EfficacyLow Hypoglycemic Risk
Weight NeutralLactic Acidosis/GI intolerance
Low Cost
If A1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference – choice dependent on a variety of patient and disease specific factors).
Sulfonylurea Thiazolidinedione DPP-4 Inhibitor SGLT-2 Inhibitor GLP-1 Receptor Agonist
Insulin (basal)
Efficacy……………………Hypo Risk………………..Weight………………..…..Side Effects………….…..Cost…………………….…
High….……………….Moderate risk……….gain…………….……..hypoglycemia……….Low.……………………
high………………….low Risk……………..Gain………………….Edema,CHF,Fx’s……Cost…………………
Intermediate.……….Low risk.…………….neutral………………..rare……………………high……………………
Efficacy……………….Hypo Risk…………….Weight………………..Side Effects………….Cost……………………
Intermediate.……….Low risk………………losing…………………GU, dehydration…….high……………………
high…………….…….Low risk………………losing………………..GI………………….….high……………………
HighestHigh riskgainhypoglycemiavariable
If A1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference – choice dependent on a variety of patient and disease-specific factors).
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Sulfonylurea Thiazolidinedione DPP-4 Inhibitor SGLT-2 Inhibitor GLP-1 Receptor Agonist
Insulin (basal)
TZD
DPP-4 i
GLP-1 RA
SGLT-2 i
SU
TZD
SGLT-2 i
Insulin
If A1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables; (2) on GLP- RA, add basal insuin; or (3) on optimally titrated basal insulin, add GLP-1 RA or mealtime insulin. In refractory patients,
consider adding TZD or SGLT-2i:
Insulin
SU
DPP-4 i
SGLT-2 i
GLP-1 RA
SU
TZD
InsulinDPP-4 i
SU
TZD
Insulin
TZD
DPP-4 i
GLP-1 RA
Insulin
SGLT-2 i
Insulin (basal) + or GLP-1 RAMealtime Insulin
Metformin+
American Diabetes Association. Approaches to glycemic treatment . Sec. 7. InStandards of Medical Care in Diabetes – 2015. Diabetes Care2015;38(Suppl. 1):S41-S48.
4/27/2015
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CNS: Promotes satiety and reduction of appetite
cell: Stimulates glucose-dependent insulin secretion; Increases cell mass
cell: Inhibits glucagon secretion in a glucose- dependent fashion
Liver: Reduces hepatic glucose output by inhibiting glucagon release
Stomach: Slows gastric emptying times
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GLP-1Inactive
GLP-1 Actions
Mixed meal
GLPGLP-1Active
Plasma
IntestinalGLP-1release DPP-4
Excreted by kidneys
Rapid inactivation(>80% of pool)
DPP-4 = Dipeptidyl peptidase-4GLP-1 = Glucagon-like Peptide-1
Deacon CF, et al. Diabetes. 1995;44:1126-1131.
GLP-1Inactive
GLP-1 Actions
Mixed meal
GLPGLP-1Active
Plasma
IntestinalGLP-1release DPP-4
Excreted by kidneys
Rapid inactivation(>80% of pool)
DPP-4 = Dipeptidyl peptidase-4GLP-1 = Glucagon-like Peptide-1
Deacon CF, et al. Diabetes. 1995;44:1126-1131.
GLP-1 Agonists
DPP-4 Inhibitors
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Generic TradeDosing
ScheduleMixing
Required
Pre-injection waiting
time
DosingSmallest Needle
Size
Needles included
Use with basal
insulin
Auto Injector
AlbiglutideTanzeum
QW YesYes 15-30 minutes
30mg, 50mg
29-gauge, 5mm thin-
walled needle
Yes Yes No
Dulaglutide Trulicity QW No None0.75mg, 1.5mg
Built in to device
29g, 5 mm needle
Yes part of device
NoCurrently
studies are evaluating
Yes
Exenatide Byetta BID No None5mcg, 10mcg
32 gauge, 4mm
needleNo Yes No
Exenatideextended release
BydureonKit
QW Yes None 2mg23-gauge,
8mm needle
Yes
NoCurrently
studies are evaluating
No
Exenatideextended release
BydureonPen
QW Yes None 2mg23-gauge,
7mm needle
Yes
NoCurrently
studies are evaluating
No
Liraglutide Victoza QD No None.6, 1.2, 1.8mg
32 gauge, 4mm
needleYes Yes No
Generic TradeDosing
ScheduleMixing
Required
Pre-injection waiting
time
DosingSmallest Needle
Size
Needles included
Use with basal
insulin
Auto Injector
AlbiglutideTanzeum
QW YesYes 15-30 minutes
30mg, 50mg
29-gauge, 5mm thin-
walled needle
Yes Yes No
Dulaglutide Trulicity QW No None0.75mg, 1.5mg
Built in to device
29g, 5 mm needle
Yes part of device
NoCurrently
studies are evaluating
Yes
Exenatide Byetta BID No None5mcg, 10mcg
32 gauge, 4mm
needleNo Yes No
Exenatideextended release
BydureonKit
QW Yes None 2mg23-gauge,
8mm needle
Yes
NoCurrently
studies are evaluating
No
Exenatideextended release
BydureonPen
QW Yes None 2mg23-gauge,
7mm needle
Yes
NoCurrently
studies are evaluating
No
Liraglutide Victoza QD No None.6, 1.2, 1.8mg
32 gauge, 4mm
needleYes Yes No
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Generic TradeDosing
ScheduleMixing
Required
Pre-injection waiting
time
DosingSmallest Needle
Size
Needles included
Use with basal
insulin
Auto Injector
AlbiglutideTanzeum
QW YesYes 15-30 minutes
30mg, 50mg
29-gauge, 5mm thin-
walled needle
Yes Yes No
Dulaglutide Trulicity QW No None0.75mg, 1.5mg
Built in to device
29g, 5 mm needle
Yes part of device
NoCurrently
studies are evaluating
Yes
Exenatide Byetta BID No None5mcg, 10mcg
32 gauge, 4mm
needleNo Yes No
Exenatideextended release
BydureonKit
QW Yes None 2mg23-gauge,
8mm needle
Yes
NoCurrently
studies are evaluating
No
Exenatideextended release
BydureonPen
QW Yes None 2mg23-gauge,
7mm needle
Yes
NoCurrently
studies are evaluating
No
Liraglutide Victoza QD No None.6, 1.2, 1.8mg
32 gauge, 4mm
needleYes Yes No
Generic TradeDosing
ScheduleWeeks of
StudyA1c Reduction (Monotherapy) Fasting Blood Sugar Reduction
AlbiglutideTanzeum
QW 5230 mg = -0.7%50 mg = -0.9%
30 mg = -16 mg/dl50 mg = -25 mg/dl
Dulaglutide Trulicity QW 260.75mg = -0.7%1.5mg = -0.8%
0.75mg = -26mg/dl1.5mg = -29mg/dl
Exenatide Byetta BID 245 mcg = -0.7%10 mcg = -0.9%
5 mcg = -17mg/dl10 mcg = -19mg/dl
Exenatideextended release
BydureonKit
QW 24 2mg = -1.6% 2mg = -25 mg/dl
Exenatideextended release
BydureonPen
QW
Liraglutide Victoza QD 521.2 mg = -0.8%1.8 mg = -1.1%
1.2 mg = -15 mg/dl1.8 mg = -26 mg/dl
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Nausea and diarrhea are possible (early) Hypoglycemia more likely if used with
secretogogues Injection site reactions Pregnancy Category C Pancreatitis risk (low but identifiable) Risk of Thyroid C-cell Tumors Renal Precautions
Contraindications:◦ Medullary Thyroid Carcinoma◦ Hypersensitivity◦ Multiple Endocrine Neoplasia (Type 2) Thyroid Parathyroid Adrenal
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More medications◦ Lixisenatide – once-daily injectable ◦ Oral GLP-1 – Eligen Technology using low molecular
weight compounds – increase lipophilicity1.◦ Combinations with Insulin – number of companies
working on this◦ Very Long Acting GLP-1’s - on the order of 3,6, and
12 months
http://www.ncbi.nlm.nih.gov/pubmed/16305420 (Accessed 1/24/2015
Healthy eating, wt. control, increased physical activity & diabetes educationMetformin
High EfficacyLow Hypoglycemic Risk
Weight NeutralLactic Acidosis/GI intolerance
Low Cost
If A1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference – choice dependent on a variety of patient and disease specific factors).
Sulfonylurea Thiazolidinedione DPP-4 Inhibitor SGLT-2 Inhibitor GLP-1 Receptor Agonist
Insulin (basal)
Efficacy……………………Hypo Risk………………..Weight………………..…..Side Effects………….…..Cost…………………….…
High….……………….Moderate risk……….gain…………….……..hypoglycemia……….Low.……………………
high………………….low Risk……………..Gain………………….Edema,CHF,Fx’s……Cost…………………
Intermediate.……….Low risk.…………….neutral………………..rare……………………high……………………
Efficacy……………….Hypo Risk…………….Weight………………..Side Effects………….Cost……………………
Intermediate.……….Low risk………………losing…………………GU, dehydration…….high……………………
high…………….…….Low risk………………losing………………..GI………………….….high……………………
HighestHigh riskgainhypoglycemiavariable
If A1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference – choice dependent on a variety of patient and disease-specific factors).
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Metformin+
Sulfonylurea Thiazolidinedione DPP-4 Inhibitor SGLT-2 Inhibitor GLP-1 Receptor Agonist
Insulin (basal)
TZD
DPP-4 i
GLP-1 RA
SGLT-2 i
SU
TZD
SGLT-2 i
Insulin
If A1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables; (2) on GLP- RA, add basal insuin; or (3) on optimally titrated basal insulin, add GLP-1 RA or mealtime insulin. In refractory patients,
consider adding TZD or SGLT-2i:
Insulin
SU
DPP-4 i
SGLT-2 i
GLP-1 RA
SU
TZD
InsulinDPP-4 i
SU
TZD
Insulin
TZD
DPP-4 i
GLP-1 RA
Insulin
SGLT-2 i
Insulin (basal) + or GLP-1 RAMealtime Insulin
Metformin+
American Diabetes Association. Approaches to glycemic treatment . Sec. 7. InStandards of Medical Care in Diabetes – 2015. Diabetes Care2015;38(Suppl. 1):S41-S48.
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Why?
The failure to initiate or intensify therapy in a defined time among patients who have not attained clinical goals and who would likely
benefit from intensification
Beckley ET. Doc News. 2006;3:4.
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Khunti K, et.al. Clinical Inertia in People with Type 2 Diabetes. Diabetes Care 2013; 36:3411-3417..Khunti K, et.al. Clinical Inertia in People with Type 2 Diabetes. Diabetes Care 2013; 36:3411-3417..
Intensification to Insulin
Years Mean A1c at Intensification
1 OAD 7.1y 8.7%
2 OADs 6.1y 9.1%
3 OADs 6.0y 9.7%
Retrospective cohort Study based on 81,573 people with T2DM between Jan 2004-Dec 2006
The failure to initiate or intensify therapy in a defined time among patients who have not attained clinical goals and who would likely
benefit from intensification
Beckley ET. Doc News. 2006;3:4.
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Physician Time Hypoglycemia Weight Inadequacy Futility
Patient Perceptions Aversions Physical Cultural
Koerbel G, Korytkowski M. Insulin-Therapy Resistance Practical Diabetology. June 2003:36-40.Magwire ML. Am J Ther. 2011;18:392-402.Koerbel G, Korytkowski M. Insulin-Therapy Resistance Practical Diabetology. June 2003:36-40.Magwire ML. Am J Ther. 2011;18:392-402.
Identify Personal Obstacles Restore Sense of Personal Control Enhance Self-Efficacy Address Emotional Issues Discuss the Risks of Hypoglycemia Discuss Injection Fears Reinforce the positive aspects of insulin use Refer patient for Diabetes Self Management
Education Provide Ongoing Support
Polonsky WH, et al. Clin Diabetes. 2004;22:147-50.Funnell MM. Clin Diabetes. 2007;25:36-8.
Funnell MM, et al. Diabetes Care. 2012;Suppl 1:S97-104.
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The Future
Now:◦ Inhaled Insulin◦ Concentrated Insulins
Future:◦ Glucokinase Activators◦ Ultra-Long Acting Insulins◦ Ultra-Rapid Acting Insulins◦ Biosimilar Insulins
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Garber AJ et al. Endocr Pract. 2013;19(Suppl 2):1-48.
Clinical Practice Guidelines can give us important insights into the management of our patients with T2DM
It is important to consider patient specific factors when choosing therapy for our patients
There are many newer classes of medication for T2DM, including GLP-1’s that need to be considered
There are important patient and provider barriers to identify when choosing subcutaneous/injection therapy for our patients
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Our understanding of diabetes continues to evolve, the number of tools that we have continue to grow and the environment in
which we care for our patients continues to change…..
we have to keep up.
Questions?
