Biphasic insulin aspart 30 metformin vs once-daily insulin glargine glimepiride

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Biphasic insulin aspart 30 metformin vs
once-daily insulin glargine glimepiride
A study in people with type 2 diabetes

• Kann P, Regulski M, Medding J, Ligthelm R

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Introduction

• In patients failing on oral antidiabetic (OAD)
  medication, insulin therapy is frequently started
  by adding
• a basal insulin, or
• a premixed insulin preparation.

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Insulin analogues insulin aspart
Pro
Asp
Phe
Gly
Arg
Phe
Tyr
Glu
Thr
Gly
Asp
B30
Cys
B28
Lys
Thr
Val
Asn
Cys
A21
Tyr
Leu
Gly
A1
Asn
Tyr
Ile
Glu
Leu
Val
Leu
Ala
Glu
Gln
Glu
Gln
Tyr
Val
Leu
Cys
Ser
Cys
Thr
Ser
Leu
Cys
Ile
His
Ser
Gly
Cys
Leu
B1
His
Gln
Asn
Val
Phe
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Insulin analogues

• Biphasic insulin aspart 30 comprises

30 soluble, rapid-acting insulin aspart
70 protaminated insulin aspart, which is
intermediate-acting
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Insulin analogues

• Insulin glargine
• long-acting human insulin analogue
• structural changes delay absorption
• allows a relatively constant basal insulin supply
  following subcutaneous injection

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Insulin glargine
Phe
Gly
Arg
Phe
Tyr
Glu
Thr
Gly
Pro
A21
B30
Cys
Lys
Thr
Val
Cys
Gly
Tyr
Arg
Leu
Asn
Gly
A1
Asn
Arg
Tyr
Ile
Glu
Leu
Val
Leu
Ala
Glu
Gln
Glu
Gln
Tyr
Val
Leu
Cys
Ser
Cys
Thr
Ser
Leu
Cys
Ile
His
Ser
Gly
Cys
Gly
Leu
B1
His
Gln
Asn
Val
Phe
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Aim

• The objective of this study was to compare
  efficacy and tolerability of two start-up insulin
  regimens in patients with type 2 diabetes failing
  on OADs

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Trial design
Randomised, open-label, parallel study
BIAsp 30 twice daily metformin (BIAsp/met)
Insulin glargine once daily glimepiride
(Glargine/glim)
2-week screeningperiod
20-week treatment period
6-week titrationperiod
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Study endpoints

• Primary
• HbA1c after 26 weeks
• Secondary
• HbA1c after 16 weeks
• Prandial increment in plasma glucose
• Fasting plasma glucose
• 7-point plasma glucose profiles
• Body Mass Index
• Safety

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Patient characteristics
No of patients (n, ITT population) BIAsp/met (128) Glarg/glim (127)
Age 61.5 9.3 61.0 8.9
Gender ( male) 53 49
BMI (kg/m2) 29.9 4.9 30.6 4.4
Time since diagnosis (yrs) 10.3 7.5 10.2 6.7
HbA1c () 9.2 1.4 8.9 1.3
All values are mean SD unless stated otherwise
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Greater reduction in HbA1c with BIAsp/met than
Glarg/glim
BIAsp/met Glarg/glim
-0.5 p0.0002
Reduction from baseline to end-of-trial
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Lower HbA1c after 26 weeks with BIAsp 30/met than
Glarg/glim
HbA1c ()
p0.01
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Greater reduction in HbA1c with BIAsp/met than
Glarg/glim after 16 weeks
-0.5 p0.0001
D HbA1c ()
Reduction from baseline to week 17
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Percentage of patients achievingHbA1c lt 7
Patients at target ()
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Absolute change of FPG after 26 weeks
FPG (mmol/l)
p0.23
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7-point PG profile at trial end
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Absolute change in PG from baseline
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Mean prandial increment in PG
Change from baseline in mean prandial PG increment
p0.0002
plt0.0001
Mean prandial PG increment at EOT
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Overall hypoglycaemia during treatment
BIAsp/met(n 123) Glargine/glim (n122)
Major Subjects () Events (n) 0.81 1 0.82 1
Minor Subjects () Events (n) 20.33 60.7 9.02 20
Symptomatic Subjects () Events (n) 10.57 34 6.56 17
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BMI and weight change

BIAsp/met
Glargine/glim
Significant change from baseline (95 CI 0.81
2.2)
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End of trial treatment doses
Treatment Median daily dose (U/mg)
BIAsp 30 25 U
Glargine 28 U
Metformin 2000 mg
Glimepiride 4 mg
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Results summary

• Compared with Glarg/glim, BIAsp 30/met
• improved glycaemia to a greater extent
• was associated with same number of major
  hypoglycaemia (1 event) but more minor
  hypoglycaemia
• had no significant effect on weight

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Conclusions

• Adding insulin to type 2 patients failing with
  OAD can improve glycaemic control
• BIAsp/met may be a more preferable option to
  Glarg/glim when initiating insulin in patients
  with type 2 diabetes

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