Insulins in Type 2 Diabetes Mellitus

Dr. Sharat S. Kolke MD, DNB

When Why

How?

Dynamic nature of normal endogenous insulin secretion. Main components are basal insulin and postprandial insulin.

Ser

um

Insu

lin le

vel

Endogenous insulin

Time (hrs)

cell function at diagnosis and later……

Insulin over the ages….

1922 – Insulin discovered by Banting and Best

1923 – Insulin commercially available

1930s to 1940s – PZI, NPH and lente insulin

1960s to 1970s – Purified animal insulin

1980s – Human insulin by r DNA technology

2000 – Insulin analogues

Onset of Action (h)

Peak (h) Duration of Action (h)

 Regular0.5-1 2-4 6-10

   NPH 1-3 5-7 10-20

   Lente® 1-3 4-8 10-20

   Ultralente®

2-4 Unpredictable

16-20

Human insulin

   Lispro (Humalog®)

5 min-15 min

1 4-5

   Aspart (Novolog®)

5 min-15 min

1 4-5

   Glargine (Lantus®)

1-2 Flat ~24

Analogs

Dynamic nature of normal endogenous insulin secretion. Main components are basal insulin and postprandial insulin.

Ser

um

Insu

lin le

vel

Endogenous insulin

Time (hrs)

Insulin treatment Regimens Split pre mixed

Basal bolus

Split self mixed

Split self mixed

Effective for helping patients achieve glycemic control

Problems with mixing technique

Inaccurate dosing ratios

Reducing the effectiveness of the short-acting insulin.

Self pre-mixed

The benefits of premixed insulin formulations

(such as a human insulin 30/70 mixed suspension)

1. reduced errors

2. and improved dosing accuracy

3. 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 meals and 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

meal

Ideally, each component should come from a different insulin, with a specific profile

Barriers Reassurances with Insulin Therapy

Insulin resistance Improves insulin sensitivity by reducing glucotoxicity

Cardiovascular (CV) risk

No evidence of atherosclerotic effects

May reduce CV risk

Weight gain Modest

Hypoglycemia Rarely causes severe events

Practical guidelines – Combination regimens

Average 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 Metformin

For marked insulin resistance

Combination of Metformin + Glitazone

If target HbA1c <7% not achieved

Try triple oral therapy

or

Add evening basal insulin while continuing oral therapy

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) monitoring

Increase 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 – Starting Basal 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?

Practical guidelines – Advancing to Basal Bolus insulin

Are Analogues better?

How do they differ from conventional insulin?

The main difference is usually in the ‘time action profile’. This means the new insulin

either works faster and for shorter periods or have a more prolonged course of action for

twenty four hours.

What are the different analogues available?

Insulin Lispro (Humalog)Insulin Aspart (Novorapid R)

Insulin Glargine (Lantus)Insulin Detemir (Levemir)

What are the potential benefits? 

• Timing of injections – can be injected immediately before meals

• Risk of hypoglycaemia may be less particularly nocturnal hypoglycaemia

• Compliance may be improved with use of once daily long acting analogues

• The need for snacks between meals may be reduced with 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.