DEVOTE: A landmark safety outcomes trial
for Tresiba® U-1001
DEVOTE: A landmark safety outcomes trial for Tresiba® U-1001
In patients with T2D and ASCVD
DEVOTE is the first safety outcomes trial evaluating the noninferiority in risk of major adverse cardiovascular events (MACEa) with Tresiba® U-100 vs insulin glargine U-100.1,2 Tresiba® U-100 achieved the primary composite outcome, demonstrating no increased risk of MACE vs insulin glargine U-100.1 The secondary confirmatory endpoints compared rates and incidence of severeb hypoglycemia between the 2 products.1
Percentage of patients experiencing MACE1,a:
8.5% in the Tresiba® U-100 group
9.3% in the insulin glargine U-100 group
aMACE=cardiovascular death, nonfatal MI, or nonfatal stroke.
bSevere hypoglycemia was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions and during which plasma glucose concentration may not have been available, but where neurological recovery following the return of plasma glucose to normal was considered sufficient evidence that the event was induced by a low plasma glucose concentration.1
In adult patients with type 2 diabetes and ASCVD
Tresiba® U-100 is the only basal insulin that has demonstrated significantly lower rates of severe hypoglycemia vs insulin glargine U-1001,3-6
Rate of severe hypoglycemia events1
Tresiba® U-100
3.70 events
per 100 patient-yearsc
4.9%
of patients experienced ≥1 severe hypoglycemia event(s)d
Insulin glargine U-100
6.25 events
per 100 patient-yearsc
6.6%
of patients experienced ≥1 severe hypoglycemia event(s)d
cEstimated rate ratio: 0.60. [95% CI, 0.48 to 0.76]; P<0.001 for superiority.1,2
dAbsolute difference: 1.7%. Estimated odds ratio, 0.73 [95% CI, 0.60 to 0.89]; P<0.001 for superiority.1,2
Glycemic control between the 2 groups was similar at baseline and throughout the trial.1
Study design
DEVOTE: A landmark safety outcomes trial for Tresiba® U-100
DEVOTE was a landmark treat-to-target trial of 7637 patients with inadequately controlled type 2 diabetes and ASCVD.1
7637 patients
Inclusion criteria1,2,e:
- Type 2 diabetes1
- Current treatment with ≥1 oral or injectable antidiabetic agent2
- A1C ≥7.0% OR A1C <7.0% and current treatment with ≥20 U/day basal insulin2
- Age ≥50 years and ≥1 coexisting cardiovascular OR renal condition or age ≥60 years and ≥1 cardiovascular risk factor1,2
Exclusion criteria7,e:
- Acute coronary or cerebrovascular event in previous 60 days
- Planned coronary, carotid, or peripheral artery revascularization
- Chronic heart failure NYHA class IV
- Current hemodialysis or peritoneal dialysis or eGFR <30 mL/min/1.73 m2 per CKD-EPI
- End-stage liver disease
eThis is not an exhaustive list of the inclusion and exclusion criteria.
Duration 2.0 years (median)
Primary composite endpoint
Time to first MACE composed of:
CV death
Nonfatal MI
Nonfatal stroke
FPG target was 71 to 90 mg/dL with an alternative target of 90 to 126 mg/dL for vulnerable patients, at investigators’ discretion.2,f
fPatients determined their FPG by performing 3 pre-breakfast SMBG tests on the 2 days before and on the day of dose adjustment each week. The lowest of the 3 pre-breakfast SMBG values was used to adjust their dose of basal insulin each week.
Secondary confirmatory endpoints:
The number and incidence of severe hypoglycemic events1
Patient characteristics at baseline1,2:
- Mean age: 65 years1
- Mean diabetes duration: 16.4 years1
- Mean A1C: 8.4%1
- % of patients on insulin therapy: 83.92
Change in A1C level2:
There was no significant difference between treatment groups throughout the trial; at 24 months, A1C was 7.5% in both groups. ETD 0.01% (95% CI, –0.05 to 0.07); P=0.78 in post hoc analysis.
ASCVD=atherosclerotic cardiovascular disease; CKD-EPl=Chronic Kidney Disease Epidemiology Collaboration; CV=cardiovascular; eGFR=estimated glomerular filtration rate; MI=myocardial infarction; NYHA=New York Heart Association; T2D=type 2 diabetes.
