New Medications for Type 2 Diabetes

https://learn.extension.org/events/2144

This material is based upon work supported by the National Institute of Food and Agriculture, U.S. Department of Agriculture, and the Office of Family

Readiness Policy, U.S. Department of Defense under Award Numbers 2010-48869-20685, 2012-48755-20306, and 2014-48770-22587.

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https://learn.extension.org/events/2122 Find slides and additional resources under ‘event materials’

Main Objective

Talk about new medications for the treatment of DM

1. SGLT2 inhibitors

2. GLP-1 receptor agonists

3. New insulin formulation

New Medications for the Treatment of Type 2 Diabetes

Curtis Triplitt, PharmD, CDE Texas Diabetes Institute, University Health System

Associate Professor, Clinical, University of Texas Health Science Center at San Antonio

San Antonio, TX

Pathophysiologic Defects in Type 2 Diabetes: The Ominous Octet

Decreased Incretin Effect

Neurotransmitter Dysfunction

Islet b-cell Impaired

Insulin

Secretion

Decreased

Glucose

Uptake

Islet a-cell

Increased

Glucagon

Secretion

Increased Lipolysis

Increased

Glucose

Reabsorption

Increased

HGP

DeFronzo RA. Diabetes. 2009;58(4):773-795.

Hyperglycemia

-GLP-1 agonist -DPP-4 inhibitor -SU

-Insulin

(180 L/day) (1000 mg/L)=180 g/day

10%

Glucose

No Glucose

S1

S3

Glucose Regulation by the Kidney

90%

SGLT= Sodium-glucose

co-transport

SGLT-1

SGLT-2

Renal Glucose Handling After SGLT-2 Inhibition

Uri

nar

y G

luco

se E

xcre

tio

n

(g/

day

)

150

100

50

100 200 300 400

Plasma Glucose (mg/dL)

Normal Threshold

0 0

Diabetes Threshold

SGLT-2 Inhibition

Mean plasma glucose (mg/dL)

Ferrannini E, et al. J Clin Invest. 2014;124:499-508.

Gly

co

su

ria

(g

/h)

SGLT2i

baseline

Effect of SGLT2 Inhibition

on Glycosuria

• Canagliflozin FDA approved 2013 – 100mg or 300mg PO daily

• Dapagliflozin FDA approved 2014 – 5mg or 10mg PO daily

• Empagliflozin FDA approved 2014 – 10mg or 25mg PO daily

SGLT2 inhibitors

-1

-0.8

-0.6

-0.4

-0.2

0

CANA DAPA EMPA

Canagliflozin

-26 week study

Age:55 y.o.

Duration Diabetes

6.9 years

Dapagliflozin

-24 week study

Age:~54 y.o.

Duration Diabetes:

~6 years

Met: ~1800mg/day

Empagliflozin

-24 week study

Age:~56 y.o.

Duration Diabetes:

Not stated (~6 years?)

Met: >1500mg/day

Combination with Metformin-SGLT2 inhibitors

Mean Change in HbA1c from baseline(%)

Lavalle-Gonzalez FJ et al. Diabetologia 2013;56:2582-2592 Bailey CJ et al. Lancet 2010; 375:2223-2233 Haring H-U et al. Diabetes Obes Metab

Baseline A1C ~7.9%

P 100 300 P 2.5 5 10 P 10 25

Baseline A1C ~8.0%

Baseline A1C ~7.9%

**NOT HEAD-TO-HEAD STUDIES**

-1

-0.8

-0.6

-0.4

-0.2

0

CANA DAPA EMPA

Canagliflozin -52 week study

Age:56 y.o.

Duration Diabetes

6.6 years

MET >1500mg/day

Avg. GLIM 5.6mg daily

Dapagliflozin -104 week study

Age:~58 y.o.

Duration Diabetes:

~6.3 years

MET>1500mg/day

Glipizide titrated

Empagliflozin 52 & 104 week study, 56y.o.

Background of MET

EMPA or GLIM added

Not stated (~6 years?)

Met: >1500mg/day

Combination with Sulfonylurea-SGLT2 inhibitors

Mean Change in HbA1c from baseline(%)

Cefalu W et al. Lancet 2013;382:941-950 Nauck MA et al. Diabetes Obes Metab 2014;16:1111-1120; Nauck et al Diabetes Care 2011;34:2015-2022 Ridderstrale M et al. Lancet Diabetes&Endocrine 2014; 2(9):691-700

GLIM 100 300 GLIP DAPA 10 GLIM EMPA

Baseline A1C ~7.7%

Baseline A1C 7.8%

**NOT HEAD-TO-HEAD STUDIES**

(-0.11%; P=0.016)

52

104 104

52 52 52

104 104

(-0.18%); P=0.021

52 wk

52 wk

52 wk

Warnings/Precautions

• No FDA issued Black Box Warnings

• Warnings/Cautions

• Genital Mycotic infections

• Urinary Tract Infections

• Osmotic diuretic- “water follows glucose” – Hypotension

– Impaired renal function (relative)

– Small increase in HCT and LDL-C

• Diabetic Ketoacidosis (DKA)

Genital Mycotic Infections Placebo Dapagliflozin 5mg Dapagliflozin 10mg

Overall number of patients, N

1393 1145 1193

Diagnosis of genital infection, n (%)

12 (0.9) 65 (5.7) 57 (4.8)

History of recurrent genital infection, n (%)

10 (0.7) 13 (1.1) 12 (1.0)

Prior history of recurrent genital infection with clinical diagnoses of genital infection, n (%)

1/10 (10) 3/13 (23.1) 3/12 (25.0)

Women

N 677 581 598

Diagnosed genital infection, n (%)

10 (1.5) 49 (8.4) 41 (6.9)

Men

N 716 564 595

Diagnosed genital infection, n (%)

2 (0.3) 16 (2.8) 16 (2.7)

Education on SGLT-2 Who Definitely Needs the Info?

• Technically all patients, but especially:

• History of GU infections

• Uncircumcised men

• GU infections in men are uncommon

– More likely with very high plasma glucose

– Education- often are unfamiliar with this potential, may think they have an STD

Urinary Tract Infections Pooled Dapagliflozin Data from 12 placebo controlled trials up to 24 weeks long

Placebo Dapagliflozin 5 mg

Dapagliflozin 10 mg

Overall number of patients, N

1393 1145 1193

Patients with diagnosis of UTI, n (%)

52 (3.7) 65 (5.7) 51 (4.3)

Patients with history of recurrent UTI, n (%)

35 (2.5) 23 (2.0) 34 (2.8)

Patients with a prior history of recurrent UTI with clinical diagnoses of UTI, n (%)

6/35 (17.1) 4/23 (21.1) 6/34 (17.6)

Geerlings et al. Diabetes Research and Clinical Practice 2014;103:373-381

Urinary Tract Infections- continued

• More prevalent in women

• Rates of pyelonephritis not increased:

• Dapa 5mg 0.0%

• Dapa 10mg 0.1%

• Placebo 0.1%

Geerlings et al. Diabetes Research and Clinical Practice 2014;103:373-381

SGLT-2 Inhibitors: Renal Dosing

Canagliflozin Prescribing Information. 2013. Dapagliflozin Prescribing Information. 2014. Empagliflozin Prescribing Information 2014

Agent Dosing in CKD stages 3, 4 and 5 (non-dialysis)

Canagliflozin • eGFR 45—59 ml/min/1.73m2 Do not exceed 100 mg/day PO

• eGFR < 45 ml/min/1.73m2 Do not initiate and discontinue in patients currently receiving drug

Dapagliflozin • eGFR <60 mL/min/1.73 m2

Do not initiate and/or discontinue

Empagliflozin • eGFR < 45 ml/min/1.73m2 Do not initiate and discontinue in patients currently receiving drug. No limit on dosing

• Glycemic efficacy becomes less pronounced with decreasing eGFR • If the kidney doesn’t filter as much glucose, the SGLT2i can’t

prevent reabsorption

Canagliflozin and eGFR

Yale J, et al. Poster presented at: The 73rd Scientific Session of the ADA, June 21-25, 2013, Chicago, IL.

Diabetic Ketoacidosis (DKA)

• Unknown mechanism

• Glucose values do not have to be extremely high

• There will be an anion gap

• Ketones will be positive

• Most patients are somewhat dehydrated Practical tips for now:

Do not use in Type 1 DM

Do not use in LADA or “Type 1 ½”

When admitted to hospital- STOP

What populations should we use SGLT2 inhibitors with caution?

A. Blood pressure of 105/74mmHg

B. Renal insufficiency(eGFR 62 mL/min/1.73m2)

C. Type 1 DM

D. All are correct

Question Break

Incretin Glucose Regulation

DPP=dipeptidyl peptidase; GLP=glucagon-like peptide; GIP=glucose-dependent insulinotropic polypeptide or gastric inhibitory polypeptide.

Drucker DJ et al. Lancet. 2006;368(9548):1696-1705.Nauck MA. Eur J Intern Med. 2009;20(2):S303-308.Kendal DM et al. Am J Med. 2009;122(6A):S37-S50.

Oral Intake of Glucose

Muscle

Fat

Small Intestine

Glucose

Incretins

DPP-4 enzymatic inactivation

Rapid incretin inactivation

Liver

↑ Glucose uptake

↑ Insulin

↓ Glucagon

Hepatic glucose production

↓

Pancreas

Glucose GLP-1 GIP DPP-4

GLP-1Modulate Numerous Functions in Humans

Stomach:

Helps regulate

gastric emptying

Promotes satiety and

reduces appetite

Liver:

Glucagon reduces

hepatic glucose output

(glycogenolysis)

β cells:

Enhances glucose-

dependent insulin secretion

α cells:

Postprandial

glucagon secretion

GLP-1: Secreted upon

the ingestion of food

Flint A, et al. J Clin Invest. 1998;101:515-520; Data from Drucker DJ. Diabetes. 1998;47:159-169.

GLP-1 Receptor Agonists • Actions: • DPP-4 inhibitors and GLP-1 receptor agonists

– Increases insulin secretion in a glucose-dependent manner – Suppress inappropriate glucagon secretion ONLY GLP-1 Receptor Agonists – Slow gastric emptying – Increase satiety

• Treatment options – Exenatide

• Exenatide BID • Exenatide weekly

– Liraglutide – Albiglutide – Dulaglutide – Flint A, et al. J Clin Invest. 1998;101:515-520;

Flint A, et al. J Clin Invest. 1998;101:515-520; Data from Drucker DJ. Diabetes. 1998;47:159-169

Properties/Effects Long Acting GLP-

1 agonists

Short-acting

GLP-1 agonists

DPP-4 inhibitors

Administration SQ Daily or

Weekly

SQ Twice Daily Oral Daily

Glucose-dependent insulin increase Yes Yes Yes

Glucose-dependent glucagon

decrease

Yes Yes Yes

Slows Gastric Emptying Yes Yes No

Lower hypoglycemia risk (in absence

of SU’s)

Yes Yes Yes

Effect on Body Weight Loss Loss Neutral

Effect on A1C High Efficacy Moderate Efficacy Moderate Efficacy

Effect on Fasting Plasma Glucose Good Modest Modest

Major Adverse Effects GI, nausea GI, nausea Well-tolerated

Adjustment/restriction in renal

impairment

No, but GI SE in

renally impaired

patients- Caution

Yes, avoid in

Severe/ ESRD

Yes, varies per

medication

Overview of Approved Incretin Therapies

Differences between incretin mimetics Liraglutide Exenatide* Albiglutide Dulaglutide

Dosing (SubQ) 1.2-1.8mg QD

(after initial 0.6mg QDx7d)

5-10mcg within 60 min. of AM/PM meals

30-50 mg weekly 0.75-1.5mg weekly

Half-life 13 hr 2-4 hr 5 days 5 days

Max dose 1.8 mg 10 mcg BID 50 mg weekly 1.5mg weekly

Renal elimination

No Yes No No

Homology to GLP-1

97% 53% 97% 90%

Antibodies 8.6% 44% 2.5% 2%

Other effects Less persistant nausea vs. Byetta

Greater effects on FPG vs. Byetta

Byetta-Greater effects on PPG

(*exenatide

LAR has more

effect on FPG,

less nausea)

Nausea seems

to be similar to

other agents

No reconstitution

Available one-time

use pens or pre-

filled syringes

GLP-1 RA’s • Dose

– Exenatide/Byetta® 5-10 mcg BID

– Liraglutide/Victoza® start 0.6mg daily 1.2-1.8 mg QD therapeutic

– Exenatide/LAR-Bydureon® 2 mg weekly

– Albiglutide 30-50mg weekly

– Dulaglutide 0.75-1.5mg weekly

– SQ injection in thigh, abdomen or upper arm

– Refrigerate unopened pens only

– Prime 1st use- Byetta and Victoza

• Advantages – Weight friendly – Prefilled pens – QD and weekly dosing options – Less injections (long-acting)

Exenatide IR and Liraglutide

• Exenatide- good for post-prandial control

– Compliance- make sure taking evening dose

– Space more away from meal for more satiety (up to 1-2 hours prior)

• Liraglutide- easy device to use

– Compliance- Ask: Out of 7 injections in a week(once daily), how many are you usually able to take?

Albiglutide

• Background – 97% homology to native GLP-1(7-36)

– 2 copies of a modified GLP-1 fused to human Albumin (C-terminus end of the modified GLP-1 sequence to the N-terminus of the human albumin)

– Manufactured by rDNA technology-Saccaromyces cerevisiae

– Resistant to DPP-4 metabolism- glycine replaces native GLP-1 alanine

– Gives a half-life of 3.6-6.8 days

Eperzan, EMA, Accessed 7-9-14; http://www.ema.europa.eu/docs/en_GB/document_ library/EPAR_-_Public_assessment_report/human/002735/WC500165119.pdf

Albiglutide- Efficacy

• Study #1: 3 year data, DB, PC trial – Mean A1C 8.1%, Duration DM 4 years

– A1C reduction

Albi 30mg (n=30) -0.96%, SD 0.968

Albi 50mg (n=32) -1.07%, SD 0.887

Placebo(n=14) 0.61%, SD 0.644

• Study #2: Albi 50mg weekly versus Lira 1.8mg daily at week 32 – A1C- Albi -0.78%, Lira -0.99%

(difference 0.21%; 0·08—0·34; non-inferiority p value=0·0846)

– GI SE- Albi 36%, Lira 49%

– Injection site reactions- Albi 12.9%, Lira 5.4%

Rendell M et al. ADA 74th Scientific Sessions, San Francisco, June 2014, P-959, ADA 74th Scientific Sessions, San Francisco, June 2014, P-1339 Pratley RE et al. Lancet Diabetes & Endo. 2014;2:289-297

Albiglutide • Dosing

– 30mg Weekly

– May increase to 50mg weekly

• Efficacy is somewhat less than others, so recommend increasing to 50mg daily when tolerated

Eperzan, EMA, Accessed 7-9-14; http://www.ema.europa.eu/docs/en_GB/document_ library/EPAR_-_Public_assessment_report/human/002735/WC500165119.pdf

Albiglutide

• Side Effect Profile and Warnings

• Similar to other long-acting GLP-1 RA’s

– MTC-1 case of MTC with Albi and 1 case in placebo

– Warnings- similar to other long-acting GLP-1 RA’s

• Pancreatitis

• Renal Failure- do not use if eGFR <30mL/min/1.73m2

• Hypoglycemia- if with SU, glinide, or insulin

• Hypersensitivity- mild inj. site pruritis mostly, but 1 anaphylaxis in trials

Package Insert, GSK 2014, accessed 7-9-14, http://www.gsksource.com/ gskprm/htdocs/documents/TANZEUM-PI-MG-IFU-COMBINED.PDF#nameddest=MG

Dulaglutide

• Recombinant GLP-1 Fc fusion protein linking GLP-1 analog to a human IgG4 Fc fragment

• Results in:

– Prolonged t1/2: ~5 days

– Once weekly dosing

– Important: A solution-No reconstitution needed

– Minimal renal clearance

– Low immunogenicity risk

ADA74th Scientific Sessions, San Francisco, LB-110, P-979, P-962

Dulaglutide Baseline (means)

D vs. Lira AWARD-6

D vs. Glar AWARD-2

D vs. Glar AWARD-4

HbA1c (%) 8.1 vs. 8.1 8.1 to 8.2 8.4 to 8.5

FPG (mg/dL) 167 vs. 165 NR 150-157

Age (years) 56 vs 57 56-57 59-60

Weight (kg) 94 vs 94 85-88 91-92

Duration of Diabetes (y)

7 vs 7 ~9 12-13

Background Tx Metformin ~2grams/day

Max tolerated Met and glim

Poorly controlled on conventional insulin- added lispro TID to D or G

ADA74th Scientific Sessions, San Francisco, LB-110, P-979, P-962 Dungan K. Lancet 11 July 2014 doi:10.1016/S0140-6736(14)60976-4

Dulaglutide- Results Outcomes (Means Reported)

D vs. Lira AWARD-6 (26 week)

D vs. Glar AWARD-2 (78 week)

D vs. Glar AWARD-4 (26 week)

Medication D1.5mg L1.8mg D0.75 D1.5 G D0.75 D1.5 G

HbA1C (%) -1.42 -1.36 -0.62 -0.9 -0.59 -1.59 -1.64 -1.41

Wt change (kg) -2.9 -3.6 -1.54 -1.96 1.28 @wk 52 1.6 0.6 3.7

TDD Insulin n/a NR 97 93 132

% at goal <7% 68.3 67.9 NR @wk 52 56 59 49

Other Info All reported side effects comparable between tx’s

PRO-less behavior & worry- hypoglycemia

Glargine was ~64 units/day

ADA 74th Scientific Sessions, San Francisco, LB-110, P-979, P-962 Dungan K. Lancet 11 July 2014 doi:10.1016/S0140-6736(14)60976-4

Dulaglutide- Side Effects Outcomes (%)

D vs. Lira AWARD-6 (26 week)

D vs. Glar AWARD-4

(@ 52 week)

GI (%) D1.5mg L1.8mg D0.75 D1.5 G

Nausea 20.4 18.0 17.7 25.8 3.4

Vomiting 7.3 8.3 10.6 12.2 1.7

Diarrhea 12.0 12.0 15.7 16.6 6.1

Injection Site Reaction

0.3 0.7 1.4 0.3 0.0

Hypoglycemia <70mg/dl +/- Sx,Events/ pt/yr 0.34 0.52

Severe 1.7 2.1 3.7 <70mg/dl 88.4 85.9 89.5

Other Info D/C due to SE 6% in each group No Pancreatitis or

Pancreatic CA

No Pancreatitis or Pancreatic Cancer reported

ADA74th Scientific Sessions, San Francisco, LB-110, P-979, P-962 Dungan K. Lancet 11 July 2014 doi:10.1016/S0140-6736(14)60976-4

Question Break

Head-to-Head Studies: HbA1c Study Acronym

Drugs Comparison HbA1C reduction (%)

DURATION-1 Exenatide BID -1.5

Exenatide Weekly -1.9*

DURATION-5 Exenatide BID -0.9

Exenatide Weekly -1.6*

DURATION-6 Exenatide Weekly -1.28

Liraglutide -1.48*

LEAD-6 Exenatide BID -0.79

Liraglutide -1.2*

GetGoal-X Lixisenatide daily -0.79

Exenatide BID -0.96

*Significant difference

Head-to-Head Studies: HbA1c Study

Acronym Drugs Comparison HbA1C reduction (%)

HARMONY-7 Albiglutide -0.78

Liraglutide -0.99

AWARD-1 Dulaglutide 1.5mg weekly -1.51*

Dulaglutide 0.75mg weekly -1.30*

Exenatide BID -0.99

AWARD-6 Dulaglutide -1.42 (non-inferior)

Liraglutide -1.36

*Significant difference

Though all in the same class of medications, efficacy varies per product

Head-to-Head Studies: Weight Study Acronym Drugs Comparison Weight Reduction (kg)

DURATION-1 Exenatide BID -3.7

Exenatide Weekly -3.6

DURATION-5 Exenatide BID Not Reported

Exenatide Weekly Not Reported

DURATION-6 Exenatide Weekly -2.68

Liraglutide -3.57*

LEAD-6 Exenatide BID -2.87

Liraglutide -3.24

GetGoal-X Lixisenatide daily -2.96

Exenatide BID -3.98

*Significant difference

Head-to-Head Studies: Weight Study Acronym

Drugs Comparison Weight reduction (kg)

HARMONY-7 Albiglutide -0.64

Liraglutide -2.16*

AWARD-1 Dulaglutide 1.5mg weekly -1.3

Dulaglutide 0.75mg weekly -0.3

Exenatide BID -1.07

AWARD-6 Dulaglutide -2.90

Liraglutide -3.61*

*Significant difference

Weight loss may be slightly less with albiglutide and dulaglutide

Similar among other products

Long-term Safety Concerns • Medullary Carcinoma/C-cell hyperplasia

– Rodents- only increase incidence in this model

– Humans- no increased incidence to date

– Possible- GLP-1 receptors on C-cell tumors

• Pancreatitis – No causality, but continued association

– Large observational trials do not support an increased risk

• Pancreatic Cancer – No association to date

Egan AG N Eng J Med 2014;370:794-797 Geir B JCEM 2012;97:121-131

Effect of GLP-1 RAs on CVD Risk Factors

Risk Factor

Exenatide

10 mcg BID

(3.5 years)1

Liraglutide

1.2 mg qd

(26 weeks)2

Exenatide

LAR

2.0 mg qw

(1 year)3

Albiglutide 30–50 mg qw

(32 weeks)4

Dulaglutide

1.5 mg qw

(26 weeks)5

SBP (mm Hg) –3.5* –6.7† –6.2* N/A –1.7†

DBP (mm Hg) –3.3* –2.3 –2.8* N/A –0.4

TC (mg/dL) –10.8* –8.1 7.9* ND –0.8 to –8.1‡

LDL-C (mg/dL) –11.8* –10.8† –2.2 ND –1.9 to –7.0‡

HDL-C (mg/dL) 8.5* –1.2 N/A ND N/A

Triglycerides

(mg/dL) –44.4* –14.7† –40.0* ND –12.4 to –16.8

*P <0.05 vs baseline; †P <0.005 vs placebo; ‡P <0.001 vs placebo.

1. Klonoff DC et al. Curr Med Res Opin. 2008;24(1):275–286; 2. Zinman B et al. Diabetes Care. 2009;32(7):1224–1230; 3. Bergenstal R et al. Diabetes. 2009;58(suppl 1):165-OR; 4. Pratley RE et al. Lancet Diabetes Endocrinol. 2014;2(4):289–297; 5. Nauck MA et al. Diabetes Care. 2014;37(8):2149–2158.

N/A = not available; ND = no difference vs. placebo.

Lixisenatide (not FDA approved)-Preliminary evidence-neutral for CV events

Injection Technique

Inject straight into the skin – Depress the button to release insulin into SQ tissue

Hold for 5 to 10 seconds before removing the needle from skin

Remove needle and dispose into sharps container

Always have the patient demonstrate their technique – At first education of the device

– At first follow-up visit

– At frequent intervals thereafter

Inject “straight in”

flush with skin

Exenatide BID (Byetta)

Requires a one time priming of the device

Subsequent doses can be given in the thigh, abdomen or back of the upper arms

Liraglutide (Victoza)

Requires a one-time priming of the device

Subsequent doses can be given in the thigh, abdomen, or back of the upper arms

• Dose is dialed to this marker and the button is pressed until a drop of solution is produced

• Button is held down for 6 seconds during administration

Exenatide LAR Weekly Kit (Bydureon)

4 parts (Single dose tray) – Needle

– Vial Connector

– Syringe (Diluent)

– Vial (Powder)

Complex preparation Dose can be given in the thigh, abdomen, or back

of the upper arms Dose must be given immediately Push down on plunger until it stops

Exenatide LAR Weekly Pen Device(Bydureon)

Same dosing, just new device-out “later this year”

At least 15 minutes at room temperature prior to mixing steps

Major steps in preparation

Twist until mix diluent with microspheres (audible click noted upon mixing)

Gently move pen back and forth (oscillate) at least 80 times (about 1- 1 ½ minutes)

Check Mixing Window for proper mixing-should see uniform grey color; If not - continue until uniform color seen in mixing window

Twist until dosing plunger comes out of knob and will hear a second “click”

Attach needle → ready for injection

Albiglutide (Tanzeum)

Single reconstitutable pen

Must be used within 8 hours of reconstitution

• Hold pen vertically with #1 visible • Pen is turned clockwise until a click is heard and #2 appears • Gently rock the pen side to side like a window wiper five times (0° to 180°) • If 30 mg, let rest for 15 minutes and if 50 mg, let rest for 30 minutes upright • After time has elapsed, rock the pen with similar technique five more times • Solution should be yellow in appearance • Attach the supplied needle and tap the pen gently to dislodge bubbles • Turn the pen clockwise until #3 appears • Inject into thigh, abdomen, or back of the upper arms • Button is held down for 5 seconds during administration

Dulaglutide (Trulicity)

Single prefilled syringe

– NO reconstitution necessary

Can be injected into thigh, abdomen, or back of the upper arms

• Uncap the pen • Place the pen on the desired injection area • Turn the lock ring of the pen from the locked to

unlocked position • Press and hold the button down for 5 - 10 seconds • The patient will hear a click when the button is pressed • A second click will indicate the dose was administered

Patient Education

What to expect – The most common side effects include:

• Nausea (usually mild to moderate)

• Diarrhea (loose stools)

– Tips to minimize/eliminate nausea • Eat smaller meals, stop eating when full

• Avoid overeating!!!!!

• Cut down on fatty foods

• Wear comfortable clothes. – Tight waistbands can make you feel worse

– If nausea is severe or you have mid-abdominal pain, call your health care professional

GI Side Effect Management: Drug • Longer acting preparations tend to have less GI

side effects

• Start at lowest dose (If possible)

• Short-acting: – Do not titrate dose until GI SE are gone

– Exenatide BID • Take close to meals and eat slow

• Long-acting: – Skip doses until GI SE are gone

U-300 Insulin Glargine • Only available in pens

– 300 U/mL, 1.5 mL

– Max dose per injection is 80 units with current pen

– New pen in development will allow a max dose of 240 units

– Just dial the prescribed dose; no conversion needed like U-500

• U-300 glargine pen is white and green with the concentration highlighted in orange to distinguish it from U-100 glargine

1. http://www.pdr.net/full-prescribing-information/toujeo?druglabelid=3688. Accessed March 26, 2015. 2. http://www.pdr.net/drug-summary/lantus?druglabelid=520. Accessed March 26, 2015.

U-300 Glargine vs U-100 Glargine in T2DM: Meta-Analysis of Phase III Trials EDITION 1, 2, & 3

Baseline to Month 6

RR (95% CI) Glar U-300

(N=1247)

Glar U-100

(N=1249)

A1C (%), LS mean –1.02 –1.02 NS

Weight (kg), LS mean 0.49 0.75 P = 0.058

Any hypo in 24 hr* 67.8 73.8 0.92 (0.87–0.96)

Any nocturnal hypo* 31.7 41.3 0.77 (0.69–0.85)

Confirmed BG <54 mg/dl

or severe hypo* 26.9 33.3 0.81 (0.72–0.90)

Confirmed nocturnal BG

<54 mg/dl or severe hypo* 9.7 13.2 0.73 (0.59–0.91)

*% people ≥1 event. LS = least squares; RR = relative risk; BG = blood glucose; CI = confidence interval.

Ritzel RA, et al. Presentation 963, 50th EASD Annual Meeting, September 15-19, 2014, Vienna, Austria.

U-300 Insulin Glargine Dosing • Insulin-Naive Patients:

– Type 1 Diabetes – Start with 1/3 to 1/2 of the total daily insulin dose calculated by using 0.2-0.4 U/kg/day; give the remainder of the total daily insulin dose as a short-acting insulin and divide between each daily meal

– Type 2 Diabetes – Start with 0.2 U/kg/day

• Type 1 or Type 2 Diabetes:

– Changing from once daily long-acting or intermediate-acting insulin:

• Initial dose can be the same as the once daily long-acting dose; for patients controlled on U-100 insulin glargine, expect that a higher daily dose of U-300 glargine will be needed to maintain the same level of glycemic control

– Changing from twice daily NPH insulin:

• Initial dose is 80% of the total daily NPH dosage

What is the major side effect of GLP-1 receptor agonists?

• Medullary thyroid cancer

a. Pancreatic cancer

b. Osmotic diuresis

c. GI side effects

Which of the following are side effects of SGLT2 inhibitors?

a. GU mycotic infections

b. Hypotension

c. Slight worsening of eGFR

d. Diabetic Ketoacidosis

e. All of the above

Question Break

Take Home Points for Dietitians

• SGLT2 inhibitors – watch fluid/electrolyte balance; signs of DKA; renal function; LDL-C

• GLP-1 receptor agonists – watch/counsel for N/V/D

• Glargine 300 – less risk of hypoglycemia; less weight gain

Disclosures

Speaker’s Bureau

• AstraZeneca

• Boehringer Ingelheim

Thank You

Texas Diabetes Institute, San Antonio, TX

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*Available until August 25, 2016. The applicability of

information presented today may change with new

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MFLN Nutrition and Wellness Upcoming Event

• 5-2-1-0 Healthy Messaging Campaign

• Date: Tuesday, September 22

• Time: 11:00am Eastern

• Location: https://learn.extension.org/events/2145 to register.

• For more information on MFLN-Nutrition and Wellness go to:

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Find all upcoming and recorded webinars

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Personal Finance

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This material is based upon work supported by the National Institute of Food and Agriculture, U.S. Department of Agriculture, and the Office of Family

Readiness Policy, U.S. Department of Defense under Award Numbers 2010-48869-20685, 2012-48755-20306, and 2014-48770-22587.