Diabetes Update 2016 - Washington State Pharmacy Association

5/15/2016
Diabetes Update 2016
Josh Neumiller, PharmD, CDE, FASCP
Associate Professor
Department of Pharmacotherapy
Washington State University
Disclosures to Participants
Conflicts of Interest and Financial Relationships Disclosures:
Presenter:
Joshua J. Neumiller, PharmD, CDE, FASCP • Speakers Bureau: Novo Nordisk
• Advisory Board/Consultant: Eli Lilly, Sanofi
• Research Grant Support to WSU: AstraZeneca, Johnson & Johnson, Merck, Novo Nordisk.
Learning Objectives
1. Identify new and emerging insulin therapies for the treatment of diabetes mellitus;
2. Discuss recently approved non‐insulin therapies for the treatment of diabetes mellitus; and
3. Discuss emerging safety considerations for select antidiabetic medications.
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PK Profile of Currently Available Insulins
Inhaled insulin
Aspart, Lispro, Glulisine
Plasma Insulin Levels
Regular
Intermediate (NPH insulin)
Long (Insulin detemir)
Long (Insulin glargine)
Ultralong (U300 glargine;
Insulin degludec)
0
2
4
6
8
10
12
16
14
18
20
22
24
26
28
30
32
34
36
Time (hours)
Adapted from Hirsh IB. NEJM. 2005;352:174-183. Flood TM. J
Fam Pract. 2007;56(suppl 1):S1-S12.
http://www.pdr.net/full-prescribinginformation/afrezza?druglabelid=3540. Accessed April 5, 2015.
U‐300 Insulin Glargine (Toujeo®)
• U‐300 insulin glargine offers a smaller depot surface area leading to a reduced rate of absorption
• Provides a flatter and prolonged pharmacokinetic and pharmacodynamic profiles and more consistency
• Half‐life is ~23 hours • Duration of action ≤36 hours
• Associated with less hypoglycemia
Garber AJ. Diabetes Obesity Metab; [Epub ahead of print; published online 31 Oct 2013].
Owens DR, et al. Diabetes Metab Res Rev. 2014;30(2):104-19.
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PK and PD of U‐300 (Toujeo®) vs U‐100 Insulin Glargine (Lantus®)
INS
[µU/mL-1]
20
GIR
[mg/kg-1/min-1]
25
3
15
10
5
LLOQ
0
Gla-100 0.4 U/kg-1
Gla-300 0.4 U/kg-1
2
N = 30
1
0
0
6
12
18
24
Time (h)
36
30
Becker RH, et al. Diabetes Care. 2014;pii:DC_140006.
U‐300 vs U‐100 Glargine in T2DM
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 hours
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)
Ritzel R, et al. Diabetes Obes Metab. 2015;17(9):859-867.
Insulin Glargine U100 vs U300 in T2DM
8.4
Glargine U100
Glargine U300
8.0
7.8
7.6
7.4
7.2
10
8
6
4
2
0
‐1.02%
LSM Difference, 0.00%c
(95% CI, ‐0.08–0.07)
‐1.02%
7.0
Baseline
Week 12
Month 6
•Weight gain –Glargine U100, +0.79 kg
–Glargine U300, +0.51 kg
–LSM Difference, ‐0.28 kgb
Cumulative Mean Eventsd
A1c, %
8.2
Cumulative Mean Eventsd
Meta‐Analysis of 3 Phase 3 Studies
Any Time of Day, 24 h
Annual Rate Ratio U300/U100, 15.22/17.73=0.86b
(95% CI, 0.77–0.97)
Glargine U100
Glargine U300
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Nocturnal, 00:00‐05:59 h
2.0
Annual Rate Ratio U300/U100, 2.10/3.06=0.69a
1.5
(95% CI, 0.57–0.84)
1.0
0.5
0
Glargine U100
Glargine U300
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Weeks of Treatment
aP<0.001; bP<0.05; cP=NS; dConfirmed
hypoglycemia (≤70 mg/dL) or severe hypoglycemia.
N=1247 patients treated with glargine U300 and 1249 treated with glargine U100 in 3 phase 3 EDITION studies.
Ritzel R, et al. Diabetes Obes Metab. 2015;17(9):859-867.
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Flexible vs Fixed Dosing U‐300 Glargine: Sub‐Studies of Phase 3 Trials
6-Month Treatment Period
(main study)
6-Month Extension Period
(main study)
U-300 once daily
every 24 ± 3 h
U-300 once daily
every 24 h
sub-study
U-300 once daily
every 24 h
6 months (randomization, sub-study)
Edition 2 Sub-Study
N = 109
N = 89
100
Percentage of
Injections (%)
9 months (end of sub-study)
Edition 1 Sub-Study
Flexible dosing
80
Fixed dosing
60
• No difference in A1C
between flexible- vs
fixed-dosing
• No difference in
severe or nocturnal
hypoglycemia within
each sub-study
40
20
0
24 ± <1 h 24 ± 1-3 h 24 ± >3 h
24 ± <1 h 24 ± 1-3 h 24 ± >3 h
Ritzel R, et al. Presentation 919-P 74th ADA Scientific Sessions
June 13-17, 2014, San Francisco, CA.
U‐300 Insulin Glargine (Toujeo®): Determining Starting Dose (and Dose Conversion) in T2DM
Prior Treatment:
Start with:
Once‐daily basal insulin 1:1 conversion*
Twice‐daily NPH
80% of total daily NPH dose
No current basal insulin 0.2 units/kg
• 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
U‐300 Insulin Glargine Prescribing Information. Available at: http://products.sanofi.us/toujeo/toujeo.pdf
Insulin Degludec (Tresiba®)
Subcutaneous depot
[Zn2+ ]
Insulin degludec multihexamers
Zinc diffuses slowly, causing individual hexamers to disassemble, releasing
monomers. Monomers are absorbed from the depot into the circulation.
Slow
release
Jonassen I et al. Pharm Res. 2012;29(8):2104–1214.
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Insulin Degludec U100 vs Insulin
Glargine U100 (T1DM)
Day‐to‐Day Variability in AUCGIR, CV%
250
Degludec U100 0.4 U/kg
Glargine U100 0.4 U/kg
200
150
100
50
0
0–2
2–4
4–6
6–8
8–10
10–12 12–14 14–16 16–18 18–20 20–22 22–24
Time Interval, h
Within‐subject variability for AUCGIR,0‐24h,SS was 4 times lower for insulin degludec
(CV, 20%) compared with insulin glargine (CV, 82%); P<0.0001.
Heise T, et al. Diabetes Obes Metab. 2012;14(9):859‐864.
BEGIN Basal‐Bolus Type 2
Change in HbA1c
Confirmed Nocturnal Hypoglycemia
Garber A et al. Lancet. 2012;379(9825):1498–1507.
Flexible vs Fixed Dosing of Insulin Degludec (Tresiba®)
Meneghini L, et al. Diabetes Care 2013;36:858‐864.
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Insulin Degludec (Tresiba®): Determining a Starting Dose in T2DM
Prior Treatment:
Long or Intermediate‐
acting insulin
No current basal insulin
Start with:
Same unit dose as the current total daily dose
10 units once daily
*Adjust doses in 3‐4 day intervals
• Only available in pens
• 100 units/mL or 200 units/mL
• Just dial the prescribed dose; no “conversion” needed
http://www.novo‐pi.com/tresiba.pdf
Insulin Glargine U100 vs Insulin Glargine Follow‐On U100 in T2DM
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Insulin Glargine U100 vs Insulin Glargine Follow‐On U100 in T2DM
•Hypoglycemic events/patient year: glargine U100, 22.3; glargine equivalent U100, 21.3
•Severe hypoglycemic events/patient year: glargine U100, 0.01; glargine equivalent U100, 0.04
•Weight gain: glargine U100, +2.0 kg; glargine equivalent U100, +1.8 kg
Case Study: Insulin glargine
Date: 11-28-2015
Rx
Patient: Mr. BG
Insulin glargine (Lantus) 100 units/mL
6 units SQ daily every evening
Refills: PRN
D. Feelgood
Substitution Permitted
Dispense as Written
Acute Care ISMP Medication Safety Alert. Volume 21; Issue 2. January 28, 2016.
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Case Study: Insulin glargine – Caution with Communication of Concentrated Insulins
Date: 11-28-2015
Rx
Patient: Mr. BG
Insulin glargine (Lantus) 100 units/mL
6 units SQ daily every evening
Refills: PRN
D. Feelgood
Substitution Permitted
Dispense as Written
• Patient received 100 units of insulin glargine instead of the correct dose of 6 units
• List of home medications listed the product concentration prior to the dose
• ISMP Recommendations:
• Risk for overdose is high with the introduction of concentrated insulins if the order lists the product’s concentration before the dose
• List the drug name, patient‐specific dose, and directions for use on the first line
• List concentration and other specific instructions below
Acute Care ISMP Medication Safety Alert. Volume 21; Issue 2. January 28, 2016.
U‐500 insulin pen
• Recommended for use in T1DM or T2DM who require more than 200 units/day
• Same size as other KwikPens, but is aqua in color
• Dialed in 5‐unit increments
• Contains 1,500 units of insulin
Treatment Targets for Type 2 Diabetes
Islet -cell
Decreased
Incretin Effect
Impaired
Insulin Secretion
Increased
Lipolysis
Islet -cell
Increased Glucose
Reabsorption
Increased
Glucagon Secretion
Increased
HGP
Neurotransmitter
Dysfunction
Decreased Glucose
Uptake
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SGLT‐2 Inhibition
Chao EC, et al. Nat Rev Drug Discovery 2010;9:551-559.
SGLT‐2 Inhibitor Key Considerations
• Unique MOA – have been studied in combination with a variety of other medication classes
• Oral administration
• Low hypoglycemia risk as monotherapy – caution when used with secretagogues or insulin
• Can result in weight loss and modest decrease in BP
• First medication demonstrating CV benefit from this class (Empagliflozin)*
• Key SE’s to be aware of:
– Genital mycotic infections – UTIs
– Orthostasis (especially in elderly, CKD, diuretic use)
• Watch volume status
EMPA‐REG OUTCOME:Cardiovascular
Outcomes and Death from Any Cause.
Zinman B et al. N Engl J Med 2015;373:2117-2128
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SGLT‐2 Inhibitors: Renal Dosing
Agent
Dosing in CKD stages 3, 4 and 5 (non‐dialysis)
Canagliflozin
(Invokana®)
•
eGFR ≥ 60 ml/min/1.73m2
No dosage adjustment needed
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
“If the kidneys don’t see the •
•
glucose, they don’t pee the glucose.”
Dapagliflozin
(FarxigaTM)
Do not initiate and discontinue with eGFR <60 mL/min/1.73 m2
Empagliflozin
(Jardiance®)
•
•
eGFR ≥ 45 ml/min/1.73m2
No dosage adjustment needed
eGFR < 45 ml/min/1.73m2
Do not initiate and discontinue in patients currently receiving drug
Canagliflozin Prescribing Information. 2013.
Dapagliflozin Prescribing Information. 2014.
Empagliflozin Prescribing Information. 2014
Woo V, et al. Poster presented at: The 73rd Scientific Session of the ADA, June 21‐25, 2013, Chicago, IL.
Kohan DE, et al. Kidney Int. 2013; doi: 10.1038/ki.2013.356. [Epub ahead of print]
http://www.fda.gov/Drugs/DrugSafety/ucm475463.htm
Euglycemic DKA Case Series Report
Peters AL, et al. Diabetes Care 2015;38:1687‐1693.
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Euglycemic DKA with SGLT‐2 Inhibitors: FDA Recommendations
• Evaluate for the presence of acidosis, including ketoacidosis, in patients experiencing signs or symptoms of acidosis; discontinue SGLT2 inhibitors if acidosis is confirmed; and take appropriate measures to correct the acidosis and to monitor glucose levels.
• Supportive medical care should be instituted to treat and correct factors that may have precipitated or contributed to the metabolic acidosis.
• Inform patients and caregivers of the signs and symptoms of metabolic acidosis, such as tachypnea or hyperventilation, anorexia, abdominal pain, nausea, vomiting, lethargy, or mental status changes, and instruct them to seek medical attention immediately if they experience the signs or symptoms.
• The metabolic acidosis accompanied by elevation in urine or serum ketones in the reported cases was not associated with the very high glucose levels that are typical for diabetic ketoacidosis.
Available at: http://www.fda.gov/Drugs/DrugSafety/ucm446845.htm
Metformin and Lactic Acidosis
• Incidence of lactic acidosis in a pooled analysis of 347 studies with >70,000 patient‐years of metformin use vs. > 55,000 patient‐years of no metformin use
• 4.3 per 100,000 metformin‐treated patient years
• 5.4 per 100,000 non‐metformin treated patient years
• No significant difference in lactate levels
Salpeter S, et al. Cochrane Database Syst Rev. 2010; 4:CD002967.
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Are Strict SCr Thresholds Appropriate?
• Prospective, randomized study in patients with mild renal dysfunction (SCr = 1.5‐2.5 mg/dL)
• Continued metformin use (n=198) vs. discontinued metformin (n=195) and followed for 4 years
• Baseline mean SCr = 1.8 mg/dL (both groups)
• Plasma lactate concentrations increased equally in both groups (1.5 mmol/L at baseline to 1.66 vs. 1.63 mmol/L, respectively)
• No participants developed lactic acidosis
• Non‐Met group more likely to gain weight and receive SU therapy
Rachmani R, et al. Eur J Intern Med. 2002;13(7):428‐433.
FDA Labeling Changes Summary for Metformin
• Before starting metformin, obtain the patient’s eGFR.
• Vs. SCr also accounts for the patient’s age, gender, race and/or weight
• Metformin is contraindicated in patients with an eGFR below 30 mL/minute/1.73 m2.
• Starting metformin in patients with an eGFR between 30‐45 mL/minute/1.73 m2 is not recommended.
• Obtain an eGFR at least annually in all patients taking metformin. • In patients at increased risk for the development of renal impairment such as the elderly, renal function should be assessed more frequently.
• In patients taking metformin whose eGFR later falls below 45 mL/minute/1.73 m2, assess the benefits and risks of continuing treatment. Discontinue metformin if the patient’s eGFR later falls below 30 mL/minute/1.73 m2.
• Discontinue metformin: • at the time of or before an iodinated contrast imaging procedure in patients with an eGFR
between 30 and 60 mL/minute/1.73 m2
• in patients with a history of liver disease, alcoholism, or heart failure
• in patients who will be administered intra‐arterial iodinated contrast
• Re‐evaluate eGFR 48 hours after the imaging procedure; restart metformin if renal function is stable.
Available at: http://www.fda.gov/Drugs/DrugSafety/ucm493244.htm
Metformin and Renal Impairment
• eGFR may be a more appropriate measure
• Vs. SCr also accounts for the patient’s age, gender, race and/or weight
eGFR (mL/min/1.73m2)
Proposed Action3
≥60
• No renal contraindication to metformin (regardless of serum creatinine)
• Monitor renal function annually
<60 and ≥45
• Continue use
• Increase renal function monitoring (every 3‐6 months)
<45 and ≥30
•
•
•
•
<30
• Stop metformin
Prescribe metformin with caution
Use lower dose (eg, 50% or half‐maximal dose)
Closely monitor renal function (every 3 months)
Do not initiate metformin therapy
Salpeter S, et al. Cochrane Database Syst Rev. 2010; 4:CD002967; Rachmani R, et al. Eur J Intern Med. 2002;13(7):428-433.;
Lipska KJ, et al. Diabetes Care. 2011;34(6):1431-1437.; Inzucchi SE et al. JAMA. 2014;312(24):2668-2675.
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GLP‐1 Enhancement
GLP-1 secretion is impaired in Type 2 diabetes
Natural GLP-1 has extremely short half-life
Block DPP-4 to slow the
enzymatic degradation of
GLP-1:
Sitagliptin (Januvia®)
Saxagliptin (Onglyza®)
Linagliptin (Tradjenta®)
Alogliptin (Nesina)
Add GLP-1 analogues with
longer half-life:
Exenatide (Byetta®)
Liraglutide (Victoza®)
Exenatide ER (Bydureon®)
Albiglutide (Tanzeum®)
Dulaglutide (Trulicity®)
DPP‐4 Heart Failure Data
• Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR) trial
• Enrolled 16,492 patients with T2DM and established CV disease or at high risk for CV disease
• More patients randomized to saxagliptin (289/8280, 3.5%) were hospitalized for heart failure versus those randomized to placebo (228/8212, 2.8%)
• Estimated hazard ratio: 1.27; 95% CI: 1.07‐1.51
• The Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome (EXAMINE) trial
• Enrolled 5,380 patients with established CV disease who had a recent ACS event
• More patients randomized to alogliptin (106/2701, 3.9%) experienced at least one hospitalization for heart failure compared to those randomized to placebo (89/2679, 3.3%)
• Potential risk factors: history of heart failure or renal impairment
• FDA Recommendation: HCPs should consider discontinuing these drugs in patients who develop heart failure and monitor their diabetes control.
Available at: http://www.fda.gov/Drugs/DrugSafety/ucm486096.htm
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Improving Prandial Hyperglycemia
AACE/ACE Recommendations
Glycemic Control Not at Goal
Intensify (prandial control) Add GLP‐1 RA
Add Prandial Insulin
Or SGLT‐2 inhibitor
Or DPP‐4 inhibitor
Basal Plus 1, Plus 2, Plus 3
or Basal Bolus
Insulin Titration Every 2‐3 days to reach glycemic goal
• Increase prandial dose by 10% or 1‐2 units if 2‐hour PPG or next premeal glucose is consistently >140 mg/dL
• If hypoglycemia develops, reduce TDD basal and/or prandial insulin by:
– 10% to 20% if blood glucose is consistently <70 mg/dL
– 20% to 40% if hypoglycemia is severe or blood glucose is consistently <40 mg/dL
Garber AJ, et al. Endocr Pract. 2016;22(1):84-113.
3+
(Consider initial GLP-1 RA trial)
Add 1 rapid insulin injection
before largest meal
Change to premixed insulin
twice daily
Initiate, Adjust, and Monitor
for Hypoglycemia
Initiate, Adjust, and Monitor
for Hypoglycemia
If not controlled,
consider
basal-bolus
Add ≥2 rapid insulin
injections before meals
(“basal-bolus”)
If not controlled,
consider
basal-bolus
Moderate
2
If not controlled after FPG target is reached (or if dose >0.5 U/kg/day),
treat PPG excursions with mealtime insulin.
High
# Injections
When Basal Insulin ± Oral Agents Do Not Achieve Target Glycemia
Complexity
ADA/EASD Position Statement
Initiate, Adjust, and Monitor
for Hypoglycemia
Flexibility
More Flexible
Less Flexible
Inzucchi SE, et al. Diabetes Care. 2015;38(1):140-149.
Combining GLP‐1 RA and Basal Insulin Analogs
Complementary Actions
Basal Insulin Analogs
GLP‐1 RAs
• Simple to initiate
• Simple to initiate
• Can control FPG and PPG
• Control nocturnal hyperglycemia and FPG
• Do not impair α‐cell response to hypoglycemia (reduce severe hypoglycemia)
• Lower hypoglycemia risk than NPH
• Modest weight increase (1 to 3 kg)
• Weight‐lowering
• Achieve A1c targets in ~50%‐60%
• Achieve A1c targets in ~40%‐60% Additive Effects
Potential Future Options:
Grunberger G. J Diabetes. 2013;5(3):241‐253
Holst JJ, Vilsbøll T. Diabetes Obes Metab. 2013;15(1):3‐14
• Insulin GLP‐1RA Fixed‐Dose Combinations:
• Insulin Degludec + Liraglutide
• Insulin Glargine + Lixisenatide
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GLP‐1 RAs + Basal Insulin vs Basal‐Bolus Insulin: A Meta‐analysis
Weighted Mean
Difference (95% CI)
Weight, %
‐0.03 (‐0.17 to 0.11)
‐0.16 (‐0.33 to 0.01)
‐0.11 (‐0.23 to 0.01)
‐0.10 (‐0.17 to ‐0.02)
32.25
22.50
45.25
100.00
Hypoglycemia Risk
Relative Risk (95% CI)
Weight, %
Diamant et al (2014)
Rosenstock et al (2014)
Shao et al (2014)
Overall (I2=0.0%, P=0.526)
0.70 (0.55 to 0.90)
0.65 (0.50 to 0.83)
0.14 (0.01 to 2.65)
0.67 (0.56 to 0.80)
50.42
49.21
0.37
100.00
Weighted Mean
Difference (95% CI)
Weight, %
‐4.60 (‐5.33 to ‐3.87)
‐1.50 (‐2.06 to ‐0.94)
‐11.07 (‐12.59 to ‐9.55)
‐5.66 (‐9.80 to ‐1.51)
33.66
33.81
32.53
100.00
∆A1c
Diamant et al (2014)
Rosenstock et al (2014)
Shao et al (2014)
Overall (I2=0.0%, P=0.470)
-0.3 -0.2 -0.1
0.008
0
0.1 0.2 0.3
1
4.9
∆Body Weight
Diamant et al (2014)
Rosenstock et al (2014)
Shao et al (2014)
Overall (I2=98.7%, P<0.0001)
-10 -6
Favors GLP-1 RA + Basal Insulin
-2 0 2
6
10
Favors Basal-Bolus Insulin
Eng C, et al. Lancet. 2014;384(9961):2228‐2234.
GLP‐1 RA or Bolus Insulin
With Optimized Basal Insulin for T2DM
Lispro
1.0
Exenatide BID
ΔFPG, mmol/L
ΔA1c, %
0.0
‐0.5
‐1.0
‐1.5
0.0
a a
a a
a
a
a
a
18
24
‐1.0
0 2 4 6 8
12
18
24
Weeks Since Randomization
Blood Glucose, mmol/Lc
0.5
‐0.5
30
9
7
5
12
Weeks Since Randomization
ΔBody Weight, kg
11
0 2 4 6 8
Pre Post Pre Post Pre Post 3AM
Breakfast
Lunch
Dinner
3
2
1
0
‐1
‐2
‐3
30
b b
b
b
b
b
b
0 2 4 6 8
12
18
24
30
b
Weeks Since Randomization
Compared with lispro, exenatide caused more GI issues (47% vs 13%), but fewer non‐nocturnal hypoglycemic episodes (15% vs 34%)
aP<0.01 for exenatide BID vs insulin lispro; bP<0.001 for exenatide BID vs insulin lispro; cOpen symbols and dashed lines are at
randomization, whereas closed symbols and solids lines are at 30 weeks.
N=627 patients with insufficient A1c control after 12 weeks of basal insulin optimization (mean background dosing was insulin
glargine 61 units/day and metformin 2000 mg/day).
Diamant M, et al. Diabetes Care. 2014;37(10):2763-2773.
GLP‐1 RA/Basal Insulin Fixed‐Ratio Combination
Glycemic Control in DUAL I
10
IDegLira
IDeg
Initial A1c
Lira 1.8 mg
Final A1c
9.5
9.6
8.8
9
8.3
A1c, %
8.0
8
7.2
7.6 7.7
7
6
7.1
6.4 6.4
6.0
a
≤7.5
7.0
6.9
a
a
a
>8.5–≤9.0
>9.0
Total Trial
Population
190 107 86
833 413 414
Baseline A1c Category, %
n=
208 124 117
299 123 139
6.4
a
a
>7.5–≤8.5
7.1
a
6.6
a
a
a
5
6.7
6.2
7.2 7.3
136 59 72
aP<0.01.
N=1660 insulin-naïve adults with T2DM (A1c, 8.3%; BMI, 31.2 kg/m2) uncontrolled on oral agents assigned to IDegLira, insulin
degludec, or liraglutide 1.8 mg daily (DUAL I Extension).
Gough SC, et al. Lancet Diabetes Endocrinol. 2014;2(11):885-893; Rodbard HW, et al. Diabetes Obes Metab. 2016;18(1):40-48.
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Confirmed Hypoglycemia Events Per 100 Patient‐Years
GLP‐1 RA/Basal Insulin Fixed‐Ratio Combination
IDegLira
500
IDeg
a
b
c
a
a
NS
300
Lira
a
a
400
a
NS
200
100
0
≤7.5
>7.5–≤8.5
>8.5–≤9.0
>9.0
Total Trial
Population
190 107 86
7.0 7.6 7.7
825 412 412
6.4 6.9 7.1
Baseline A1c Category, %
n= 205 123 127
Final A1c, % 6.0 6.4 6.4
295 123 138
6.2 6.7 7.1
135 59 71
6.6 7.2 7.3
Fewer patients in the IDegLira group reported GI adverse events than in the liraglutide group (nausea, 8.8% vs 19.7%)
aP<0.0001; bP=0.001; cP<0.05.
N=1660 insulin-naïve adults with T2DM (A1c, 8.3%; BMI, 31.2 kg/m2) uncontrolled on oral agents assigned to IDegLira, insulin
degludec, or liraglutide 1.8 mg daily (DUAL I Extension).
Gough SC, et al. Lancet Diabetes Endocrinol. 2014;2(11):885-893; Rodbard HW, et al. Diabetes Obes Metab. 2016;18(1):40-48.
Thank you!
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