diabetes update 20165/15/2016 1 diabetes update 2016 josh neumiller, pharmd, cde, fascp associate...
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5/15/2016
1
Diabetes Update 2016
Josh Neumiller, PharmD, CDE, FASCPAssociate ProfessorDepartment of PharmacotherapyWashington 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
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-prescribing-information/afrezza?druglabelid=3540. Accessed April 5, 2015.
0 12 16 20 2484
Pla
sma
Insu
lin
Lev
els
2 14 18 22106
Intermediate (NPH insulin)
Long (Insulin detemir)
Long (Insulin glargine)
Time (hours)26 28 30 32 34 36
Ultralong (U300 glargine; Insulin degludec)
Aspart, Lispro, Glulisine
Regular
Inhaled insulin
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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LLOQ
PK and PD of U‐300 (Toujeo®) vs U‐100 Insulin Glargine (Lantus®)
Becker RH, et al. Diabetes Care. 2014;pii:DC_140006.
0
GIR
[mg
/kg
-1/m
in-1
] 3
1
Time (h)
2
36
Gla-100 0.4 U/kg-1
Gla-300 0.4 U/kg-1
24181260 30
0
INS
[µU
/mL
-1]
25
5
15
20
10
N = 30
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 T2DMMeta‐Analysis of 3 Phase 3 Studies
Cumulative
Mean
Events
dCumulative
Mean
Events
d
Weeks of Treatment
Any Time of Day, 24 h
00
4
810
282 18 244 6 8 12
6
2
262220161410
00
0.5
1.5
2.0
282 18 244 6 8 12
1.0
262220161410
Nocturnal, 00:00‐05:59 h
A1c, %
Glargine U100
Glargine U300
7.0
7.8
8.2
8.4
8.0
7.6
7.4
7.2
Baseline Week 12 Month 6
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.
Glargine U100
Glargine U300
‐1.02%
‐1.02%LSM Difference, 0.00%c
(95% CI, ‐0.08–0.07) Annual Rate Ratio U300/U100, 2.10/3.06=0.69a(95% CI, 0.57–0.84)
Annual Rate Ratio U300/U100, 15.22/17.73=0.86b
(95% CI, 0.77–0.97)
Glargine U100
Glargine U300
•Weight gain –Glargine U100, +0.79 kg–Glargine U300, +0.51 kg–LSM Difference, ‐0.28 kgb
•Weight gain –Glargine U100, +0.79 kg–Glargine U300, +0.51 kg–LSM Difference, ‐0.28 kgb
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Flexible vs Fixed Dosing U‐300 Glargine: Sub‐Studies of Phase 3 Trials
Ritzel R, et al. Presentation 919-P 74th ADA Scientific Sessions June 13-17, 2014, San Francisco, CA.
• No difference in A1C between flexible- vs fixed-dosing
• No difference in severe or nocturnal hypoglycemia within each sub-study
Edition 1 Sub-StudyN = 109
Per
cen
tag
e o
fIn
ject
ion
s (%
)
20
100
024 ± <1 h
80
60
40
24 ± 1-3 h 24 ± >3 h 24 ± <1 h 24 ± 1-3 h 24 ± >3 h
Edition 2 Sub-StudyN = 89
Flexible dosing
Fixed dosing
6 months (randomization, sub-study)
U-300 once dailyevery 24 ± 3 h
U-300 once dailyevery 24 h
9 months (end of sub-study)
sub-study
6-Month Treatment Period(main study)
6-Month Extension Period(main study)
U-300 once dailyevery 24 h
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
U‐300 Insulin Glargine Prescribing Information. Available at: http://products.sanofi.us/toujeo/toujeo.pdf
• 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
Insulin Degludec (Tresiba®)
[Zn2+ ]
Insulin degludec
multihexamers
Zinc diffuses slowly, causing individual hexamers to disassemble, releasing
monomers.
Subcutaneous depot
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 InsulinGlargine U100 (T1DM)
Day‐to‐Day Variability
in AUCGIR, CV%
Time Interval, h
Heise T, et al. Diabetes Obes Metab. 2012;14(9):859‐864.
0
50
100
150
200
250
0–2 2–4 4–6 6–8 8–10 10–12 12–14 14–16 16–18 18–20 20–22 22–24
Degludec U100 0.4 U/kg
Glargine U100 0.4 U/kg
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.
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.
BEGIN Basal‐Bolus Type 2
Garber A et al. Lancet. 2012;379(9825):1498–1507.
Confirmed Nocturnal Hypoglycemia
Change in HbA1c
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: Start with:
Long or Intermediate‐acting insulin
Same unit dose as the current total daily dose
No current basal insulin 10 units once daily
• Only available in pens• 100 units/mL or 200 units/mL• Just dial the prescribed dose; no “conversion” needed
*Adjust doses in 3‐4 day intervals
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
•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
Rx
Patient: Mr. BG
Date: 11-28-2015
Substitution Permitted Dispense as Written
Refills: PRN
Insulin glargine (Lantus) 100 units/mL
6 units SQ daily every evening
D. Feelgood
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
Rx
Patient: Mr. BG
Date: 11-28-2015
Substitution Permitted Dispense as Written
Refills: PRN
Insulin glargine (Lantus) 100 units/mL
6 units SQ daily every evening
D. Feelgood
Acute Care ISMP Medication Safety Alert. Volume 21; Issue 2. January 28, 2016.
• 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
• 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
U‐500 insulin pen
Treatment Targets for Type 2 Diabetes
Islet -cell
ImpairedInsulin Secretion
NeurotransmitterDysfunction
Decreased GlucoseUptake
Islet -cell
IncreasedGlucagon Secretion
IncreasedLipolysis
Increased GlucoseReabsorption
IncreasedHGP
DecreasedIncretin Effect
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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:CardiovascularOutcomes 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
Canagliflozin Prescribing Information. 2013.Dapagliflozin Prescribing Information. 2014.Empagliflozin Prescribing Information. 2014Woo 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]
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
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
“If the kidneys don’t see the glucose, they don’t pee the
glucose.”
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
Available at: http://www.fda.gov/Drugs/DrugSafety/ucm446845.htm
• 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.
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 eGFRbetween 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
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.
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 • 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
<30 • Stop metformin
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GLP‐1 Enhancement
GLP-1 secretion is impaired in Type 2 diabetesNatural GLP-1 has extremely short half-life
Add GLP-1 analogues with longer half-life:
Exenatide (Byetta®)
Liraglutide (Victoza®)
Exenatide ER (Bydureon®)
Albiglutide (Tanzeum®)
Dulaglutide (Trulicity®)
Block DPP-4 to slow the enzymatic degradation of GLP-1:
Sitagliptin (Januvia®)
Saxagliptin (Onglyza®)
Linagliptin (Tradjenta®)
Alogliptin (Nesina)
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 HyperglycemiaAACE/ACE Recommendations
Garber AJ, et al. Endocr Pract. 2016;22(1):84-113.
Or SGLT‐2 inhibitorOr DPP‐4 inhibitor
Intensify (prandial control)
Add GLP‐1 RAAdd Prandial Insulin
Glycemic Control Not at Goal
Basal Plus 1, Plus 2, Plus 3or Basal Bolus
• 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
Insulin Titration Every 2‐3 days to reach glycemic goal
ADA/EASD Position StatementWhen Basal Insulin ± Oral Agents Do Not Achieve Target Glycemia
Inzucchi SE, et al. Diabetes Care. 2015;38(1):140-149.
If not controlled after FPG target is reached (or if dose >0.5 U/kg/day),treat PPG excursions with mealtime insulin.
(Consider initial GLP-1 RA trial)
Add 1 rapid insulin injection before largest meal
# In
ject
ions
Com
plex
ity
2
3+
Mod
erat
eH
igh
Flexibility More Flexible Less Flexible
Change to premixed insulin twice daily
Add ≥2 rapid insulin injections before meals
(“basal-bolus”)
If not controlled, consider
basal-bolus
If not controlled, consider
basal-bolus
Initiate, Adjust, and Monitor for Hypoglycemia
Initiate, Adjust, and Monitor for Hypoglycemia
Initiate, Adjust, and Monitor for Hypoglycemia
• Simple to initiate
• Can control FPG and PPG
• Do not impair α‐cell response to hypoglycemia (reduce severe hypoglycemia)
• Weight‐lowering
• Achieve A1c targets in ~40%‐60%
• Simple to initiate
• Control nocturnal hyperglycemia and FPG
• Lower hypoglycemia risk than NPH
• Modest weight increase (1 to 3 kg)
• Achieve A1c targets in ~50%‐60%
Combining GLP‐1 RA and Basal Insulin Analogs
Grunberger G. J Diabetes. 2013;5(3):241‐253Holst JJ, Vilsbøll T. Diabetes Obes Metab. 2013;15(1):3‐14
Basal Insulin Analogs GLP‐1 RAs
Additive Effects
Complementary Actions
Potential Future Options:• Insulin GLP‐1RA Fixed‐Dose Combinations:
• Insulin Degludec + Liraglutide
• Insulin Glargine + Lixisenatide
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Hypoglycemia Risk Relative Risk (95% CI) Weight, %Diamant et al (2014) 0.70 (0.55 to 0.90) 50.42Rosenstock et al (2014) 0.65 (0.50 to 0.83) 49.21Shao et al (2014) 0.14 (0.01 to 2.65) 0.37Overall (I2=0.0%, P=0.526) 0.67 (0.56 to 0.80) 100.00
∆A1c Weighted Mean Difference (95% CI) Weight, %
Diamant et al (2014) ‐0.03 (‐0.17 to 0.11) 32.25Rosenstock et al (2014) ‐0.16 (‐0.33 to 0.01) 22.50Shao et al (2014) ‐0.11 (‐0.23 to 0.01) 45.25Overall (I2=0.0%, P=0.470) ‐0.10 (‐0.17 to ‐0.02) 100.00
GLP‐1 RAs + Basal Insulin vs Basal‐Bolus Insulin: A Meta‐analysis
Eng C, et al. Lancet. 2014;384(9961):2228‐2234.
∆Body Weight Weighted Mean Difference (95% CI) Weight, %
Diamant et al (2014) ‐4.60 (‐5.33 to ‐3.87) 33.66Rosenstock et al (2014) ‐1.50 (‐2.06 to ‐0.94) 33.81Shao et al (2014) ‐11.07 (‐12.59 to ‐9.55) 32.53Overall (I2=98.7%, P<0.0001) ‐5.66 (‐9.80 to ‐1.51) 100.00
Favors GLP-1 RA + Basal Insulin Favors Basal-Bolus Insulin
-0.3 -0.2 -0.1 0 0.1 0.2 0.3
0.008 1 4.9
-10 -6 -2 0 2 6 10
GLP‐1 RA or Bolus InsulinWith Optimized Basal Insulin for T2DM
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.
Compared with lispro, exenatide caused more GI issues (47% vs 13%), but fewer non‐nocturnal hypoglycemic episodes (15% vs 34%)
ΔA1c, %
0‐1.5
‐1.0
‐0.5
0.0
302 18 24
Lispro
Exenatide BID
Weeks Since Randomization4 6 8 12
ΔFPG,
mmol/L
0‐1.0
‐0.5
0.5
1.0
302 18 24Weeks Since Randomization
4 6 8 12
0.0
Blood Glucose,
mmol/Lc
PreBreakfast
ΔBody
Weight, kg
0‐3
0
23
302 18 24Weeks Since Randomization
4 6 8 12
1
‐1‐2
Post Pre Post Pre Post 3AMLunch Dinner
b
b
bbbbbb
a a a aa
a aa
5
7
9
11
GLP‐1 RA/Basal Insulin Fixed‐Ratio CombinationGlycemic Control in DUAL I
A1c, %
7
9
10
8
5≤7.5 >7.5–≤8.5 >8.5–≤9.0 >9.0 Total Trial
PopulationBaseline A1c Category, %
6
208 124 117 299 123 139 136 59 72 190 107 86 833 413 414n=
6.06.4 6.4
6.2
6.7
7.1
6.6
7.2 7.3 7.0
7.6 7.7
6.4
6.97.1
IDegLira IDeg Lira 1.8 mg
Initial A1c Final A1c
7.2
8.0
8.8
9.69.5
8.3
a
aa
a a
aa
a
a
a
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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GLP‐1 RA/Basal Insulin Fixed‐Ratio Combination
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.
Fewer patients in the IDegLira group reported GI adverse events than in the liraglutide group (nausea, 8.8% vs 19.7%)
Confirm
ed Hyp
oglycemia
Even
ts Per 100
Patient‐Years
300
500
400
0≤7.5 >7.5–≤8.5 >8.5–≤9.0 >9.0 Total Trial
PopulationBaseline A1c Category, %
200
205 123 127 295 123 138 135 59 71 190 107 86 825 412 412n=
IDegLira IDeg Lira
a
a
100
6.0 6.4 6.4 6.2 6.7 7.1 6.6 7.2 7.3 7.0 7.6 7.7 6.4 6.9 7.1Final A1c, %
a
NS
a
b
a
NS
a
c
Thank you!