Do your patients manage their diabetes by eating well and being active? Or do they need medication to help control their blood sugar? What medications are the most effective and what is new to the market? Tune in to this webinar to guide you through what is available and most effective to help your patients better control their type 2 diabetes. Learning Objectives: 1. Understand the current paradigm for the treatment of type 2 diabetes. 2. Compare and contrast pros and cons of newer medications for the Treatment of type 2 diabetes. 3. Modify a treatment plan correctly and efficiently based on the side effect profiles of newer medications for the treatment of type 2 diabetes.

1. 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.

2. Sign up for webinar email notifications:
www.extension.org/62831
Provide feedback and earn CEU credit with one link:
We will provide this link at the end of the webinar

3. Research and evidenced-based
professional development
through engaged online communities.
www.extension.org/militaryfamilies

4. Providing educational tools and caregiving tips for military professionals and family caregivers
Facebook.com/MFLNNutritionWellness
@MFLNNW
www.youtube.com/user/MIlFamLN
MFLN Nutrition and Wellness

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

6. Main Objective
Talk about new medications for
the treatment of DM
1. SGLT2 inhibitors
2. GLP-1 receptor agonists
3. New insulin formulation

7. 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

8. Pathophysiologic Defects in
Type 2 Diabetes: The Ominous Octet
Decreased Incretin Effect
Neurotransmitter Dysfunction
Islet b-cellImpaired
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

9. (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

10. Renal Glucose Handling After
SGLT-2 InhibitionUrinaryGlucoseExcretion
(g/day)
150
100
50
100 200 300 400
Plasma Glucose (mg/dL)
Normal
Threshold
0
0
Diabetes Threshold
SGLT-2 Inhibition

11. Mean plasma glucose (mg/dL)
Ferrannini E, et al. J Clin Invest. 2014;124:499-508.
Glycosuria(g/h)
SGLT2i
baseline
Effect of SGLT2 Inhibition
on Glycosuria

12. • 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

13. -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**

14. -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
104104
5252 52
104104
(-0.18%);
P=0.021
52
wk
52
wk
52
wk

15. 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)

16. 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)

17. 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

18. 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

19. 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

20. 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

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

22. 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

23. 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

24. Question Break

25. 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

26. 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.

27. 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

28. 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

29. 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

30. 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)

31. 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?

32. 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

33. 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

34. 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

35. 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

36. 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

37. 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

38. 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

39. 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

40. Question Break

41. 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

42. 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

43. 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

44. 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

45. 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

46. 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

47. 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

48. 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

49. 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

50. 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

51. 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

52. 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

53. 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

54. 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

55. 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

56. 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.

57. 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.

58. 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

59. What is the major side effect of GLP-
1 receptor agonists?
• Medullary thyroid cancer
a. Pancreatic cancer
b. Osmotic diuresis
c. GI side effects

60. 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

61. Question Break

62. 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

63. Disclosures
Speaker’s Bureau
•AstraZeneca
•Boehringer Ingelheim

64. Thank You
Texas Diabetes Institute, San Antonio, TX

65. Evaluation and CPEU Credit
• To receive CPEU credit please complete the evaluation
found at:
https://vte.co1.qualtrics.com/SE/?SID=SV_8dAUCdwF
VkfbOYJ
*Available until August 25, 2016. The applicability of
information presented today may change with new
research or policies after this time.

66. 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:
http://blogs.extension.org/militaryfamilies/nutrition-and-wellness/

67. Find all upcoming and recorded webinars
covering:
http://www.extension.org/62581
Personal Finance
Military Caregiving
Family Development
Family Transitions
Network Literacy
Nutrition & Wellness
Community Capacity Building
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.