new medications for type 2 diabetes
Post on 05-Apr-2022
3 Views
Preview:
TRANSCRIPT
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.
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
Research and evidenced-based
professional development
through engaged online communities.
www.extension.org/militaryfamilies
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
Available resources
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
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.
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/
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.
top related