Insulin over the ages….1922 – Insulin discovered by Banting and Best1923 – Insulin commercially available1930s to 1940s – PZI, NPH and lente insulin1960s to 1970s – Purified animal insulin1980s – Human insulin by r DNA technology2000 – Insulin analogues
Onset of Peak (h) Duration of Action (h) Action (h) Human insulin 0.5-1 2-4 6-10 Regular NPH 1-3 5-7 10-20 Lente® 1-3 4-8 10-20 Ultralente® 2-4 Unpredictable 16-20 Analogs Lispro 5 min-15 min 1 4-5(Humalog®) Aspart 5 min-15 min 1 4-5(Novolog®) Glargine 1-2 Flat ~24(Lantus®)
Serum Insulin level Endogenous insulin Time (hrs)Dynamic nature of normal endogenous insulin secretion.Main components are basal insulin and postprandialinsulin.
Split self mixedEffective for helping patients achieve glycemic controlProblems with mixing techniqueInaccurate dosing ratiosReducing the effectiveness of the short-acting insulin.
Self pre-mixedThe benefits of premixed insulin formulations(such as a human insulin 30/70 mixed suspension)1. reduced errors2. and improved dosing accuracy3. the convenience of using a single vial.
Applying the Basal/Bolus Insulin Concept Basal insulin• Nearly constant day-long insulin level• Suppress hepatic glucose production between mealsand overnight• Cover 50% of daily needs Bolus insulin (mealtime)• Immediate rise and sharp peak at 1 hour• Limit postmeal hyperglycemia• Cover 10% to 20% of total daily insulin requirement at each mealIdeally, each component should come from a different insulin,with a specific profile
Barriers Reassurances with Insulin TherapyInsulin resistance Improves insulin sensitivity by reducing glucotoxicityCardiovascular No evidence of atherosclerotic effects (CV) risk May reduce CV riskWeight gain ModestHypoglycemia Rarely causes severe events
Practical guidelines – Combination regimensAverage patient Early combination of insulin secretagogue and insulin sensitizer Most simple and cost-effective –Start low-dose, once-daily sulfonylurea with increasing doses of Metformin –Full-dose sulfonylurea in combination with maximally tolerated MetforminFor marked insulin resistance Combination of Metformin + GlitazoneIf target HbA1c <7% not achieved Try triple oral therapy or Add evening basal insulin while continuing oral therapy
Practical guidelines – Starting Basal Insulin …Continue oral agent(s) at same dosage (eventually reduce)Add single, evening insulin dose (around 10 units) Glargine (bedtime or anytime?) NPH (bedtime)Adjust dose according to fasting blood glucose (FBG) monitoringIncrease insulin dose weekly as needed Increase by 2 units if FBG >120 mg/dL Increase by 4 units if FBG >140 mg/dL Increase by 6 units if FBG >180 mg/dL
Practical guidelines – Advancing to Basal Bolus insulin Indicated when FBG acceptable but HbA1c >7% and/or SBGM before dinner >160-180 mg/dL Insulin options To glargine, add mealtime lispro or aspart To bedtime NPH, add morning NPH and mealtime lispro or aspart Oral agent options Continue sulfonylurea for endogenous secretion? Continue metformin for weight control? Continue glitazone for glycemic stability?
What are the different analogues available? Insulin Lispro (Humalog) Insulin Aspart (Novorapid R) Insulin Glargine (Lantus) Insulin Detemir (Levemir) How do they differ from conventional insulin? The main difference is usually in the ‘time action profile’. This means the new insulineither works faster and for shorter periods or have a more prolonged course of action for twenty four hours.
What are the potential benefits? • Timing of injections – can be injected immediatelybefore meals• Risk of hypoglycaemia may be less particularlynocturnal hypoglycaemia• Compliance may be improved with use of once dailylong acting analogues• The need for snacks between meals may be reducedwith short acting analogues• Some advantages in terms of weight gain
Are analogues more effective than conventional insulin? The advantage in terms of improved glycaemic control is not that great. It is possible to achieve equally good control using conventional insulin. Are they safe to use during Pregnancy?These drugs have not as yet been licensed for use in pregnancy
In conclusion….. Strict glycemic control is the only to prevent chronic complications. Strict glycemic control without hypoglycemia. Insulin regimens that closely mimic physiologic insulin secretory patterns must be used. The older conventional insulin products do not have time-action profiles that closely mimic normal secretory patterns. Analogues offer the physician the ability to closely approximate endogenous insulin secretory patterns.