Download Methods - Penn State Hershey Medical Center

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Insulin Degludec
 Ultra long action
 Due to formation of
soluble multihexamers
at the injection site from
which monomers
gradually separate and
are absorbed into
circulation
http://www.diatribe.us/issues/30/new-now-next.php

Insulin Degludec
 Results in a flat and stable
pharmacokinetic profile at
steady state.
 These characteristics may
reduce risk of
hypoglycemia
 Possibly may be given 3
times a week in type 2 DM
that are insulin-naïve
 This could help with
initiation and adherence to
treatment.
www.diabetologica.com

To assess efficacy and safety of insulin
degludec when:
 injected once daily or three times a week
 compared with insulin glargine once daily
 in insulin-naïve people with type 2 DM and
 Inadequately controlled on oral antidiabetic drugs
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16-week randomized, open-label, parallel
group phase 2 trial
Participants 18-75 years old
Type 2 DM with A1C= 7-11%
Enrolled and treated at 28 clinical sites
(Canada, India, South Africa, USA)
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Eligibility:
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Type 2DM (>3months)
18-75 years
A1C 7-11%
BMI 23-42 kg/m2
Insulin naïve
on oral agents for >2mos at stable half-maximum to
maximum doses
Excluded:
 if treated with agents that interfere with insulin
metabolism within 3 months of study (TZD, DPP-IV
inhibitors)
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Randomly allocated in 1:1:1:1: ratio by
computer generated block randomization to:
receive
 insulin degludec 3 times/wk (1U=9nmol) M,W,F
 Insulin degludec group A (1U=6nmol) daily
 Insulin degludec group B (1U=9nmol)daily
 Insulin glargine (1U=6nmol) daily
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All groups in combination with metformin.
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Before randomization:
 Participants discontinued pretrial oral drug and
underwent 2-week forced metformin-titration
period (up to 2g/day) followed by 1-week
metformin maintenance.
 Elible if able to maintain metformin 2g (or at least
1.5g/day) + have fasting glucose of >7.5 mmol/L
on 3 consecutive days (~135 mg/dL).
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Dosing
 Starting dose for daily groups: 10U
 Starting dose for degludec 3x/wk: 20U
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Insulin titrated up
 based on blood glucose before breakfast (lowest
value on 3 consecutive days)
 Used a plasma-calibrated blood glucose meter.
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Goal AM glucose = 4-6 mmol/L (~72108mg/dL)
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Primary outcome= A1C (after 16 weeks of tx)
 Goal was to determine a treatment difference in
A1C between groups
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Secondary Endpoint:
 Changes in fasting plasma glucose
 Required insulin dose
 Nine-point profiles of self monitored glucose.
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Mean A1C and fasting plasma glucose the same
across treatment groups.
A1C reduction from baseline was -1.3 to -1.5%
for all groups (and not different between groups)
At the study end, fasting glucose was the same
across groups.
The mean 9-point glucose profiles
 lower in all treatment groups compared to baseline
 Had the same overall shape for all groups.
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Starting dosing was higher in the degludec
3x/wk group and group B (due to formulation)
At 16 weeks, insulin dose was same in all
groups except group B (which was higher/kg)
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Body weight was slightly elevated in
degludec group B and glargine group.
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Hypoglycemia did NOT occur in 77-92% of
participants.
There were no differences between groups in
hypoglycemia.
The proportion of hypoglycemia in degludec
group A was lower than that in glargine group
or degludec 3x/wk group.
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There were only 2 serious adverse events:
 Aggravation of a pretrial CAD in the degludec
3x/wk group.
 Worsening paroxysmal Afib in degludec group B
(daily).
▪ Both were thought not to be related to degludec.
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Only 6 participants had side effects possibly
related to degludec (headache, dermatitis,
rash, diarrhea, edema)
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Insulin degludec can provide equivalent
glycemic control to insulin glargine without
new or increased rates of adverse events in
insulin-naïve type 2 DM.
The safety, efficacy and optimum use of
treatment regimens needs to be established.