Biphasic insulin aspart 30 + metformin vs once-daily insulin glargine + glimepiride Kann P, Regulski M, Medding J, Ligthelm R A study in people with type 2 diabetes

Slide no 2 Introduction In patients failing on oral antidiabetic (OAD) medication, insulin therapy is frequently started by adding: a basal insulin, or a premixed insulin preparation.

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

Slide no 4 Insulin analogues Biphasic insulin aspart 30 comprises: 30% soluble, rapid-acting insulin aspart 70% protaminated insulin aspart, which is intermediate-acting

Slide no 5 Insulin analogues Insulin glargine long-acting human insulin analogue structural changes delay absorption allows a relatively constant basal insulin supply following subcutaneous injection

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

Slide no 7 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

Slide no 8 Trial design BIAsp 30 twice daily + metformin (BIAsp/met) Insulin glargine once daily + glimepiride (Glargine/glim) 2-week screening period 20-week treatment period 6-week titration period Randomised, open-label, parallel study

Slide no 9 Study endpoints Primary HbA 1c after 26 weeks Secondary HbA 1c after 16 weeks Prandial increment in plasma glucose Fasting plasma glucose 7-point plasma glucose profiles Body Mass Index Safety

Slide no 10 Patient characteristics No of patients (n, ITT population) BIAsp/met (128) Glarg/glim (127) Age61.5 ± ± 8.9 Gender (% male)5349 BMI (kg/m 2 )29.9 ± ± 4.4 Time since diagnosis (yrs) 10.3 ± ± 6.7 HbA 1c (%)9.2 ± ± 1.3 All values are mean ± SD unless stated otherwise

Slide no 11 Greater reduction in HbA 1c with BIAsp/met than Glarg/glim BIAsp/met Glarg/glim -0.5% p= Reduction from baseline to end-of-trial

Slide no 12 Lower HbA 1c after 26 weeks with BIAsp 30/met than Glarg/glim p=0.01 HbA 1c (%)

Slide no 13 Greater reduction in HbA 1c with BIAsp/met than Glarg/glim after 16 weeks  HbA 1c (%) Reduction from baseline to week % p=0.0001

Slide no 14 Percentage of patients achieving HbA 1c < 7% Patients at target (%)

Slide no 15 Absolute change of FPG after 26 weeks FPG (mmol/l) p=0.23

Slide no 16 7-point PG profile at trial end

Slide no 17 Absolute change in PG from baseline

Slide no 18 Mean prandial increment in PG p< Mean prandial PG increment at EOT Change from baseline in mean prandial PG increment p=0.0002

Slide no 19 Overall hypoglycaemia during treatment BIAsp/met (n = 123) Glargine/glim (n=122) MajorSubjects (%) Events (n) MinorSubjects (%) Events (n) SymptomaticSubjects (%) Events (n)

Slide no 20 BMI and weight change Baseline End of trial BIAsp/metGlargine/glim BIAsp/metGlargine/glim * * Significant change from baseline (95% CI: 0.81; 2.2)

Slide no 21 End of trial treatment doses TreatmentMedian daily dose (U/mg) BIAsp 3025 U Glargine28 U Metformin2000 mg Glimepiride4 mg

Slide no 22 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

Slide no 23 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