Tips and Tricks for Starting and Adjusting Insulin MC MacSween

The Moncton Hospital

Progression of type 2 diabetes – Beta cell apoptosis

Natural History of Type 2 Diabetes

The Burden of Treatment Failure in Type 2 Diabetes

7%

8%

Patients spend on average of 59 months on dual oral

agents with A1C > 7.0% before insulin is initiated

9%

Brown JB. Diabetes Care July 2004.

Physiologic Insulin Secretion

Bottom Line – It’s Definitely Time to Start Insulin If :

• Decompensated diabetes – i.e. if symptomatic hyperglycemia and losing weight.

• A1C > 9.5%, FBG > 14 mmol/L, insulin is required.

• Preconception Type 2 Diabetes.

Decompensated Diabetes

May be short term insulin; 4 - 6 weeks if turns out to be new T2D.

Send GAD Antibodies if age < 40 or lean.

+/- Metformin

Bottom Line – Consider Insulin if :

• If A1C >8.5% on pharmacologic therapy.

• Ideally initiate insulin when A1C < 8.5% on oral agents so able to start with fewer injections and simplified regime.

• If contraindication or intolerances to multiple oral agents limits therapy (i.e. renal insufficiency).

Oral Agents and Insulin Initiation– What to Keep and What to Stop

• Unless contraindicated, Metformin is usually continued to decrease variability of morning glucose and to mitigate weight gain on insulin.

• May wean other oral agents if doing well on moderate doses of insulin.

• Secretagogues (i.e. SU’s) should be stopped once on meal insulin.

Choices of Insulin Regimes

• Basal intermediate or basal analog at hs.

• Basal Plus 1-2 meal doses of rapid insulin.

• Premix rapid.

• Basal bolus (MDI).

Basal Insulins: Intermediate Acting

• Humulin N, Novolin NPH: cloudy due to preservatives that allow prolonged action so half life is 14-18 hours. Less than half the price of basal analogues and no difference in A1C but some increase in nocturnal hypoglycemia.

• Must mix properly before injection by rolling and rotating pen 20 x or will risk hypoglycemia.

• 20% coefficient of variation in effect so try to avoid in type 1 diabetes.

• Vial (1000 units) is $20 or 5 cartridges (1500 units) is $8.50 each and $42 for pack of 5.

Basal Analogues

• Basalglar (biosimilar glargine, $15 per cartridge), Lantus (glargine, $18.50 per cartridge), Levemir (detemir $20).

• Smoother 24 hour profile with somewhat less nocturnal hypoglyemia vs. intermediate acting insulin.

• Clear, so no mixing required and can be given AM or HS.

• Levemir has a shorter half life so may need BID. More weight favorable but most expensive basal analog.

Rapid Acting Insulins

• Apidra (glulisine $10 per cartridge),

• Humalog (lispro, $11 per cartridge),

• NovoRapid (aspart $12 per cartridge).

• Often helpful to give 10-15 minutes ac unless glucose <5.

• Health Canada recent approval of faster insulin aspart, ‘Fiasp’.

Concentrated insulins

Injection Technique: 4 mm Pen Needles and Site Rotation

Leave needle in 10 – 12 seconds after injection

Injection Technique: Site Rotation

Starting Basal Insulin

• Not very useful if the AM glucose is the best of the day (i.e. lean elderly more insulin deficient than resistant).

• Least weight gain and hypoglycemia vs. other regimes.

• Usual starting dose is 10 units NPH, N, Lantus, Levemir or Basalglar.

• Titrate up by 1 unit every night until fasting glucose is 5 - 6 mmol/l. No further dose increase if 1 nocturnal low or 2 morning lows.

• Average hs NPH dose (+ daytime Metformin) is 42 units.

• Average Lantus dose 47 units but 30% require > 60 units.

Pitfalls

• Very high dose glargine (Lantus) 80 -100 units and persistent daytime hyperglycemia (? max 0.5 u/kg).

• Likely needs 1- 3 meal doses if glucose falls significantly overnight (BeAM factor > 3 mmol/L).

• Beware the catecholamine effect of untreated OSA causing increasing overnight glucose.

• Often can reduce very high Lantus dose 20% -30% and use this amount of insulin for divided meal doses.

Predicting Success of Daytime Oral Agents

and Bedtime Insulin

• Baseline A1C > 8.5%

45% get to goal

Baseline A1C < 8.5%

75% get to goal

Consider Basal plus One

Insulin Initiation: Multiple Injections

Premix Analogs

• Humalog Mix 25 and Mix 50 and NovaMix 30.

• Start 6-10 units BID (ac bkft and ac supper) and titrate morning dose based on before supper readings and evening dose based on AM readings.

• Must have stable meals and activity. No adjustment scale possible.

MDI

• 0.3 – 0.5 units/kg total daily dose. Use lower range if elderly, lean or renal insufficiency.

• 40% basal and 20% each meal.

• Most flexible regime but 4 injections per day. Preferred regime for Type 1 diabetes where starting dose should be 0.5 u/kg.

Meal Insulin

• Type 2 Diabetes: usually don’t need carb counting – can often give a range i.e. 10 units for a small meal and 15 units for a large meal.

• In insulin resistance often helpful to give rapid acting meal dose 15-30 minutes before the meal rather than progressively increase the dose and provoke further weight gain.

Coming Soon: Basal GLP-1 Agonist Combinations

• Lantus–Lixisenatide (LixiLan).

• Degludec–Liraglutide (iDegLira).

• GLP-1 mitigates the weight gain of insulin with excellent A1C lowering effect.

Monday

• 45 year old woman came to Sackville ER with blurry vision.

• Polyuria, nocturia and ‘some’ weight loss over past 3 weeks.

• Weight 60 kg.

• Blood glucose 37 mmol/l.

• What’s your management?

Start MDI with 0.5 units/kg (30 units/d) with 40% basal i.e. 12 units

and remainder divided for meals i.e. 6 units per meal

Wednesday

• 66 year old male with T2DM on Metformin, Diamicron MR and A1C 9.0%.

• Weight 102 kg and BMI 39.

• Doesn’t want to gain more weight.

• Doesn’t want low blood sugars. Mild gastroparesis.

HYPOGLYCEMIA

Correct Treatment

Elderly on Insulin – Mini Cog

• Clock drawing test can be used to predict who is likely to

have problems with insulin therapy

• “Write numbers on the blank clock face and draw hands on the

clock to show 10 minutes past 11 o’clock”

Trimble LA et al. Can J Diabetes 2005;29(2):102-104.

2013

Diabetes in the Elderly Checklist

INDIVIDUALIZE glycemic targets based on the above (A1C ≤ 8.5% for frail elderly) but if otherwise healthy, use the same targets as younger people

AVOID hypoglycemia in cognitive impairment

SELECT antihyperglycemic therapy carefully

caution with sulfonylureas or thiazolidinediones

Basal analogues instead of NPH or human 30/70 insulin

Premixed insulins instead of mixing insulins separately in syringe.

GIVE regular diets instead of “diabetic diets” or nutritional formulas in nursing homes

2013

Diabetes in the frail and not so frail elderly

Lean elderly are usually insulin deficient not insulin resistant so basal insulin alone often not very useful. Caution in stopping longstanding insulin – C-peptide.

Blood Glucose Meter with Rapid Acting Insulin Calculator (InsuLinx)

Memory Pens for NovoRapid

Libre Glucose Monitor

Summary: Insulin

SMBG= Self-monitoring of blood glucose Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes 2013;37(suppl 1):S1-S212. Origin Trial Investigators. NEJM 2012.;367(4):309-318.

ADVANTAGES DISADVANTAGES

Long-term experience Injection

No maximal dose Hypoglycemia risk

Multiple formulations and regimens

Weight gain

No contraindications Increased cost of SMBG

No increased CV or cancer risk

Bottom Line – It’s Definitely Time to Start Insulin if :

• Decompensated diabetes – i.e. if symptomatic hyperglycemia and losing weight.

• A1C > 9.5%, FBG > 14 mmol/L, insulin is required.

• Preconception Type 2 Diabetes.

Starting Basal Insulin

• Not very useful if the AM glucose is the best of the day (i.e. lean elderly more insulin deficient than resistant).

• Least weight gain and hypoglycemia vs. other regimes.

• Usual starting dose is 10 units NPH/N, Lantus, Levemir or Basalglar.

• Titrate up by 1 unit every night until fasting glucose is 5 - 6 mmol/l. No further dose increase if 1 nocturnal low or 2 morning lows.

• Average hs NPH dose (+ daytime Metformin) is 42 units.

• Average Lantus dose 47 units but 30% require > 60 units.

Pitfalls

• Very high dose glargine (Lantus) 80 -100 units and persistent daytime hyperglycemia (? max effect 0.5 u/kg).

• Likely needs 1- 3 meal doses if glucose falls significantly overnight (BeAM factor > 3 mmol/L). Basal Plus 1.

• Beware the catecholamine effect of untreated OSA causing increasing overnight glucose.

• Often can reduce Lantus dose 20% -30% and use this amount of insulin for divided meal doses.

Insulin Initiation: Multiple Injections

Premix Analogs

• Humalog Mix 25 and Mix 50 and NovaMix 30.

• Start 6-10 units BID (ac bkft and ac supper) and titrate morning dose based on before supper readings and evening dose based on AM readings.

• Must have stable meals and activity. No adjustment scale possible.

• Highest rate of weight gain hypoglycemia and least efficacious at A1C lowering.

MDI

• 0.3 – 0.5 units/kg total daily dose. Use lower range if elderly, lean or renal insufficiency.

• 40% basal and 20% each meal.

• Most flexible regime but 4 injections per day. Preferred regime for Type 1 diabetes where starting dose should be 0.5 u/kg.

Meal Insulin

• Type 2 Diabetes: usually don’t need carb counting – can often give a range i.e. 10 units for a small meal and 15 units for a large meal.

• Can start at 6 units per meal but if already on a large dose of basal can often start 0.1 unit/kg/meal (i.e. 90 kg start 9 units per meal) and may reduce basal dose.

• In insulin resistance often helpful to give rapid acting meal dose 15-30 minutes before the meal rather than progressively increase the dose and provoke further weight gain (unless insulin Fiasp).

Bottom Line – Consider Insulin if :

• If A1C >8.5% on pharmacologic therapy.

• Ideally initiate insulin when A1C < 8.5% on oral agents so able to start with fewer injections and simplified regime.

• If contraindications or intolerances to multiple oral agents limits therapy (i.e. renal insufficiency).

Basal Analogues

• Basalglar (biosimilar glargine, $15 per cartridge), Lantus (glargine, $18.50 per cartridge), Levemir (detemir $20).

• Smoother 24 hour profile with somewhat less nocturnal hypoglyemia vs. intermediate acting insulin.

• Clear, so no mixing required and can be given AM or HS.

• Levemir has a shorter half life so may need BID. More weight favorable but most expensive basal analog.

• Concentrated U300 glargine (Toujeo) need 14% higher dose.

Rapid Acting Insulins

• Apidra (glulisine $10 per cartridge),

• Humalog (lispro, $11 per cartridge),

• NovoRapid (aspart $12 per cartridge).

• Often helpful to give 10-15 minutes ac unless glucose <5.

• Health Canada recent approval of faster insulin aspart, ‘Fiasp’. Targeted for type 1 diabetes on MDI. Advantage of faster onset so can give immediately ac or even pc meals.

• Concentrated insulin Humalog U200 in unique pen.