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When and how to add prandial insulin to basal insulin + OADs in Type 2 diabetes


As Type 2 diabetes progresses, addition of prandial insulin will be required after basal optimisation

  • The need for prandial insulin despite optimal titration of basal insulin is indicated by:
    • FBG at or close to target 5-7 mmol/L (90-126 mg/dL) but HbA1c ≥7%
    • FBG controlled but PPBG consistently high (>8.8 mmol/L, >160 mg/dL)1
    • Unacceptably frequent or severe hypoglycaemia during basal insulin titration

Meal patterns vary among individuals with Type 2 diabetes

  • Few people eat three consistent meals with
    limited extra snacks
  • Many people eat one main meal
  • Meal patterns vary from day to day
  • Differences in physiology define blood glucose response to meals

Therefore, the same inflexible insulin regimens applied to all individuals would not be physiological

Basal Plus strategy: a logical stepwise strategy to basal-bolus

  • Add one injection of prandial insulin , starting with the main meal
  • Determine the main meal
  • 'Fix postprandial hyperglycaemia'
  • Use a flexible approach
  • Further prandial injections can be added, progressing towards basal-bolus therapy

Guidance for initiation and adjustment of Basal/Basal Plus regimen


* Basal insulin therapy considered optimised if FBG <6.1 mmol/L (<110 mg/dL) with average dose not exceeding 0.7 IU/kg

Traditional strategies to intensify insulin after basal optimisation

  • Basal bolus involves one injection of basal insulin plus prandial insulin injections at each meal:1
    • Perceived as the most physiological strategy - gold standard
    • But can prove difficult for patients to initiate and comply
  • Premixed insulins:
    • Perceived as convenient,1 with twice-daily injections versus four-times daily with basal bolus2
    • But not flexible because the fixed ratio of basal to prandial insulin requires fixed mealtimes

Replacement insulin therapy should mimic endogenous insulin profile in Type 1 diabetes mellitus (T1DM) and insulin-treated Type 2 diabetes mellitus (T2DM)

  • Combinations of 'basal' and 'prandial' insulin in a 'basal-bolus' insulin regimen are essential to maintain glycaemic control


Limitations of regular human insulin (RHI) in a basal-bolus insulin regimen

  • Slow onset of action
  • Requires administration 30-45 minutes before a meal
  • Mismatch between injection and postprandial peak
  • Risk of interprandial hypoglycaemia

Apidra® (insulin glulisine) - A novel 'rapid-acting' insulin analogue

Glulisine: a short-acting insulin analogue,

Stable monomer


LysB3 and GluB29 side chain interaction stabilises conformation

Molecular structure of insulin glulisine [rDNA origin]: Apidra®


  • impeded hexamer formation by LysB3

  • impaired but not blocked self-assembly due to GluB29

  • enhanced monomer stability due to a dipol bridge between GluB29 and GlyA1 replacement

Thus insulin glulisine exists in solution in mono-dimer equilibrium without the need to be stabilised with zinc.

Insulin uptake from subcutaneous tissue: Advantages of 'rapid-acting' insulin glulisine


Components of rapid-acting insulins


From human insulin, insulin lispro, insulin aspart and insulin glulisine summary product characteristics (SmPCs)

Glulisine is formulated with polysorbate 20 to reduce the unfolding monomers and prevent against fibril formation

  • Polysorbate 20 is a dispersing agent preventing precipitation of insulin hexamer to form fibrils (1,2,3)
  • Polysorbate 20 is added to glulisine to enhance physical stability without reducing equilibria between monomer and dimer

Key points for Apidra®

  • A novel molecular structure with two amino acid substitutions
  • A unique zinc-free formulation
  • Added polysorbate 20 enhances stability and prevents fibril formation

Pharmacokinetic and pharmacodynamic characteristics of Apidra® (insulin glulisine)

  • vs regular human insulin

  • vs insulin lispro

Absorption of insulin glulisine is twice as rapid as that of regular human insulin (RHI) in Type 1 diabetes


Insulin glulisine: Earlier glucose disposal compared to regular human insulin (RHI)


Key learning points: Apidra®

  • Provides rapid, early glucose disposal and shorter duration of action than RHI (However, at all doses, insulin glulisine was about twice as rapidly absorbed as RHI (INS-AUC0-2h: 3,792, 6,676, and 12,992 vs. 2,211, 3448, and 5,792 U.min.ml -1  ; P<0.05) and reached maximal serum concentrations in about one-half the time(INS-Tmax: 47,57, and 72 vs. 82, 104, and 119min; P<0.05)
  • Corresponding glucose disposition for insulin glulisine was twice as large within 2 h after injection than with RHI (GIR-AUC0-2h: 314,491, and 536 vs. 127,219, and 294 mg/kg; P<0.05) but was similar in extent on completion (GIR-AUCtotal: 499,1,090, and 1,476 vs. 416, 1,076, and 1,555 mg/kg; P=NS).
  • Provides better control of post-meal glucose excursions in obese Type 2 diabetes subjects

Key learning points: Type 2 diabetes and Apidra®

  • Better glycaemic control (HbA1c & PPBG) than RHI with NPH as basal insulin1
  • The majority of subjects can achieve HbA1c <7.0% with Lantus plus Apidra® in a basal-bolus regimen2

Initiation and adjustment of insulin regimens.

Insulin regimens should be designed taking lifestyle and meal schedule into account.


Timing of prandial insulin injections

  • For the most effective control of PPG excursions, Apidra® should be administered immediately before meals.
  • However, as demonstrated in the 12-week study in subjects with Type 1 diabetes, effective prandial glucose control can be achieved with Apidra® even when it is administered immediately after a meal.

Appropriate dosing of Apidra®

  • Dose titration according to self-monitored blood glucose values at 2 hours after a meal, with a target of at least <180 mg/dL.
  • Target sought avoiding hypoglycaemia.
  • Exercise following meals may necessitate a reduction in dose to avoid hypoglycaemia.

Summary: Apidra® - a novel 'rapid-acting' insulin analogue

  • The unique molecular structure provides faster absorption and onset of action, plus stability without the need for zinc
  • Advantageous pharmacokinetic/pharmacodynamic profile
    • Faster absorption, onset and shorter duration of action than RHI
    • Faster onset of action compared to insulin lispro, independent of BMI
  • Better glycaemic control in both Type 1 diabetes and Type 2 diabetes vs RHI
  • Flexible timing of injection: either pre- or post-meal

1.2.3 Study: Glargine Plus 1, 2 or 3 Doses of Glulisine


  • Insulin naïve (785 entered study, 343 randomised) with Type 2 diabetes (A1C ≥8.0%)

  • Receiving 2 or 3 OADs for ≥3 months (OADs continued except sulfonylurea)


Davidson M et al. Endocr Pract 2011;Feb 16:1-9 (E-pub).



A1C in all subjects (n=785) = 9.8 at run-in and 7.3 at randomisation




Woerle H. Arch Intern Med 2004;164:1627-32.
Monnier L and Colette C. Diabetes Metab 2006;32 (1):7-13.
Adapted from Nathan D. et al. Diabetologia 2006;49:1711-21.
Rosenstock J. Clin Cornerstone 2001;4:50-64.
McCall A. In: Insulin Therapy. Leahy J, Cefalu W, eds. New York, NY: Marcel Dekker, Inc; 2002: p193-222.
Adapted from Kruszynska YT, et al. Diabetologia 1987;30:16-21.
Wittlin SD, et al. In: Leahy JL, Cefalu WT, eds. Insulin Therapy:2002:73-85.
1:R. Becker; Diabetes Technology & Therapeutics Volume 9, Number 1, 20072: J.Brange, Journal of Pharmaceutical Sciences 1997; 86 (7); 517-525;3: J.DongJ.Mol. Biol 2003, 330:431-442; 4:RG Strickley, Pharmaceutical Research, 21,201-230, 2004
Becker RH. Diabetes Technol Ther 2007;9:109-21.
INS-AUC= insulin infusion rate - area under the curve Becker RH, et al. Diabetes Care, published online August 3, 2007. Reproduced with permission.
GIR-AUC=glucose infusion rate - area under the curve Becker RH, et al. Diabetes Care, published online August 3, 2007.
Dailey G, et al. Diabetes Care 2004;27:2363-8
Johnson M, etal. ADA 2007. Abstract 2195-PO.
Davidson M et al. Endocr Pract 2011;Feb 16:1-9 (E-pub).
Riddle MC et al. Diabetes July 2011;60:A113;
Rosenstock J et al. Diabetes July 2011;60:A20.


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