INSULINS Dr.R.Sajjad december 2018

Rapid-acting analogs Lispro Aspart Glulisine Inhaled insulin an onset of action in 5 to 15 min , peak activity in approximately 1 hour, and duration of activity of approximately 4 hours.

Inhaled insulin: An inhaled formulation of regular human insulin available. Quite convenient to carry and use. Microparticles produce peak in about 20 min with peak activity in 1 hour and a terminal half-life of 1 hour. Great interest as a technique to avoid frequent injection. Requires spirometry before initiation, at 6 months, annually thereafter. Contraindication : patients with asthma, COPD, active lung canser and smokers.

Short-acting analogs Human Regular regular insulin is approximately half as fast as the rapid –acting analogs,with onset 30 min ,peak at 2-4 hours and duration of action of 6 to 8 hours or longer.

Intermediate-acting analogs Human NPH Onset , peak, duration are about twofold greater than regular insulin, with an onset of action in 1-2 hours, a peak at 4 to 8 hours and a duration of action at 12 to 16 hours

Long –acting analogs Glargine Detemir Degludec glargine : is solubilized in acid but precipitated when neutralized in tissues on injection no consistent or distinctive peak in activity and duration of action of more than 24 hours in most paitents.

Detemir : a fatty –acid side chain has been covalently bound to the insulin molecule , remain soluble both in the vial and in tissues Duration of action of approximately 24 hours except at low doses < 20 to 30 units. Degludec : extended durations of action and less within –day and day to day variability in pharmacodynamics and promise greater reductions in hypoglycemic risk , less weight gain , potential improvments in glycemic control .

analogue insulins rather than human insulins: Approximaleiy threefold greater expense Greater convenience Both fast-acting and long- acting insulin analogues have been shown to provide a modest reduction in hypoglycemia

Premixed insulin products NPH/Regular 70/30 Lispro 50/50 Lispro 75/25 Aspart 70/30

Insulin therapy in DM1 Because the hallmark of type 1 diabetes is absent or near-absent b-cell function, insulin treatment is essential for individuals with type 1 diabetes. evidence has accumulated supporting multiple daily injections of insulin or continuous subcutaneous administration through an insulin pump as providing the best combination of effectiveness and safety for people with type 1 diabetes.

Generally, insulin requirements can be estimated based on weight, with typical doses ranging from 0.4 to 1.0 units/kg/day. Higher amounts are required during puberty, pregnancy, and medical illness.

The American diabetes association Type 1 Diabetes Sourcebook notes 0 The American diabetes association Type 1 Diabetes Sourcebook notes 0.5units/kg/day as a typical starting dose in patients with type 1 diabetes who are metabolically stable, with half administered as prandial insulin given to control blood glucose after meals and the other half as basal insulin to control glycemia in the periods between meal absorption .

Most studies comparing multiple daily injections with continuous subcutaneous insulin infusion (CSII) have been relatively small and of short duration. However, a recent systematic review and meta-analysis concluded that pump therapy has modest advantages for lowering A1C (–0.30% [95% CI –0.58 to–0.02]) and for reducing severe hypoglycemia rates in children and adults

The arrival of continuous glucose monitors to clinical practice has proven beneficial in specific circumstances. Reduction of nocturnal hypoglycemia in people with type 1 diabetes using insulin pumps with glucose sensors is improved by automatic suspension of insulin delivery at a preset glucose level.

Insulin therapy in DM2

Consider starting dual therapy when HbA1C is greater than 9%. Consider starting with combination injectable therapy when blood glucose is higher than 300 to 350 mg/dl or HbA1C is greater than 10% to 12% especialy if symptomatic or catabolic features are present,In which case basal insulin plus mealtime insulin is the preferred initial regimen.

Consider initial injectable combination ( ie,GLP1 RA +basal insulin or prandil/basal insulin ) if HbA1c>10% and/or >2% above target.

If basal insulin has been titrated to an acceptable fasting blood glucose level (or if the dose is >0.5 units/kg/day) and A1C remains above target, consider advancing to combination injectable therapy. This approach can use a GLP-1 receptor agonist added to basal insulin or multiple doses of insulin. The combination of basal insulin and GLP-1 receptor agonist has potent glucose lowering actions and less weight gain and hypoglycemia compared intensified insulin regimens.