1. Cardiovascular (CV) Safety and Severe Hypoglycemia Benefit of Insulin Degludec vs Insulin Glargine U100 in Older Patients (≥65 years) with Type 2 Diabetes (T2D): Observations from DEVOTE Richard E. Pratley1, Scott S. Emerson2, Edward Franek3, Matthew P. Gilbert4, Steven P. Marso5, Darren K. McGuire6, Thomas R. Pieber7, Neil R. Poulter8, Charlotte T. Hansen9, Melissa V. Hansen9, Thomas Mark9, Alan C. Moses10, Bernard Zinman11, on behalf of the DEVOTE Study Group
Pratley et al., ADA 2018 abstract
Presented at “Ligue Marocaine de lutte contre le diabète”, international conference on Diabetes and Nutrition , Rabat 6-8 July 2018

2. DEVOTE: trial design
Trial characteristics
Randomized, double blinded, active controlled, Treat-to-target - Event driven
Primary objective
To confirm the cardiovascular safety of insulin degludec compared to that of insulin glargine U100
Secondary objective
To assess the efficacy and safety of insulin degludec in patients with type 2 diabetes at high risk of cardiovascular events
Insulin degludec once daily (blinded vial) + Standard of care
Follow-up period
7637 patients randomized
IGlar U100 once daily (blinded vial) + Standard of care
Follow-up period
Randomization
Interim analysis
(150 MACE accrued)
End of treatment
(633 MACE accrued)
30 days
Primary endpoint
Time from randomization to first occurrence of a 3-point MACE: cardiovascular death*†, non-fatal myocardial infarction* or non-fatal stroke*
Secondary endpoints
Rate of severe hypoglycemic episodes*‡
Incidence of severe hypoglycemic episodes*‡
*Confirmed by the Event Adjudication Committee; †cardiovascular death includes undetermined cause of death; ‡severe defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. BG concentrations may not be available during an event, but neurological recovery following the return of BG to normal is considered sufficient evidence that the event was induced by a low BG concentration BG, blood glucose; MACE, major adverse cardiovascular event
Presented at “Ligue Marocaine de lutte contre le diabète”, international conference on Diabetes and Nutrition , Rabat 6-8 July 2018

3. Subgroup analyses of time to first 3-point MACE
Factor N %
Hazard ratio
[95% CI]
Insulin degludec
IGlar U100
p-value for interaction
Primary analysis
7637
100.0
0.91 [0.78; 1.06]
325
8.5
356
9.3
Sex
0.0989
Women
2859
37.4
0.76 [0.59; 0.99] 99
7.0
131
9.1
Men
4778
62.5
0.99 [0.83; 1.20]
226
9.4
225
9.5
Age at baseline
0.3570
<65 years
3682
48.2
0.84 [0.67; 1.05]
140
7.6
167
9.0
≥65 years
3955
51.7
0.97 [0.79; 1.19]
185
189
9.6
BMI
0.8335
<30 kg/m2
2499
32.7
0.93 [0.71; 1.21]
107
8.4
111
≥30 kg/m2
5127
67.1
0.90 [0.75; 1.08]
217
8.6
245
Renal function*
0.5785
Normal
1486
19.4
0.73 [0.50; 1.08] 44
6.0 61
8.2
Mild impairment
3118
40.8
0.97 [0.76; 1.24]
132
8.3
129
Moderate impairment
2704
35.4
0.96 [0.75; 1.21]
130
9.8
141
10.2
Severe impairment
214
2.8
0.76 [0.39; 1.50] 15
13.9 19
17.9
1.0
Hazard ratio [95% CI]
Favors insulin degludec
Favors IGlar U100
*As per CKD-EPI, CKD-EPI, chronic kidney disease epidemiology collaboration equation
Presented at “Ligue Marocaine de lutte contre le diabète”, international conference on Diabetes and Nutrition , Rabat 6-8 July 2018

4. Older patients subgroup analysis : hypoglycemia risk & CV Safety
Older patients had a higher risk of major adverse cardiovascular events (MACE), all-cause mortality and severe hypoglycemia, regardless of treatment.
Degludec was associated with a lower risk of severe hypoglycemia vs glargine U100, regardless of age
Pratley et al., ADA 2018 abstract
Presented at “Ligue Marocaine de lutte contre le diabète”, international conference on Diabetes and Nutrition , Rabat 6-8 July 2018

5. Summary
Treatment differences for MACE, all-cause mortality and severe hypoglycemia were similar across age groups, with no significant interactions between treatment and age group.
Degludec was associated with a lower risk of severe hypoglycemia vs glargine U100, regardless of age
This analysis supported the CV safety of Degludec and demonstrated a lower risk of severe hypoglycemia vs glargine U100 in older patients with T2D
Pratley et al., ADA 2018 abstract
Presented at “Ligue Marocaine de lutte contre le diabète”, international conference on Diabetes and Nutrition , Rabat 6-8 July 2018