Lantus®: A guide for healthcare professionals

WHAT IS LANTUS®?

Lantus is a clear, colourless solution completely soluble at pH 4.0. Microprecipitation occurs with the neutralisation of pH of Lantus in subcutaneous tissue after injection (see diagram).1-3

This mode of action results in a continuous release of Lantus, providing a smooth, peakless, predictable time/ concentration profile and a prolonged duration of action.1,4 Lantus has no prominent peak, whereas NPH has a distinct peak at 4.5 hours.4 (see diagram below).

Insulin in blood

Lantus (clear solution) pH4

Injection sitepH7.4

Micro-precipitation

Depot

Hexamers

Slow release of Lantus

Dimers

Monomers

Capillary membrane

This is a schematic interpretative diagram based on data from the Lantus Data Sheet,1 McKeage2 and Goykhman3.

The physiology of Lantus absorption.

Adapted from Lepore M, et al, 2000 and Lantus Data Sheet. Rates of glucose infusion needed to maintain target plasma glucose 7.2 mmol/L; indicative of insulin activity. Isoglycaemic clamp study in 20 C-peptide negative patients with Type 1 diabetes, cross over design testing insulin glargine and NPH at 0.3 U/kg.1, 4

Profile of Lantus vs NPH1,4

Glu

cose

infu

sion

rate

(mg

/kg

/min

)

NPH

Lantus

4

3

2

1

00 2 4 6 8 10 12 14 16 18 20 22 24

Time (h) after administration

Lantus (insulin glargine) is a recombinant human insulin analogue which is to be given subcutaneously once a day at the same time every day.1

Efficacy in Type 2 DiabetesLantus has been proven to help patients with Type 2 diabetes achieve improved HbA1c and fasting blood glucose levels. Various studies have demonstrated the efficacy of Lantus in this patient group.5-12

Average HbA1c reached with Lantus in various Type 2 Diabetes clinical trials

Baseline

Mea

n H

bA

1c (

mm

ol/

mo

l)

TREAT-TO-TARGET5 APOLLO6 LAPTOP7

Study End

75

60

45

30

15

0DURABLE9 LANMET10 INITIATE11 LIGTHELM12

ET AL.2010

90

TRIPLE THERAPY8

70.6

52.57

71.59

53.01

73.23

54.65

74.87

56.29

76.29

54.54

83.61

57.49

73.78

60.66

72.68

54.54

HypoglycaemiaPatients using Lantus report fewer hypoglycaemic episodes compared to patients using NPH insulin.1, 13 When taken at bedtime, a recent meta-analysis reported the risk of nocturnal hypoglycaemia was approximately halved with Lantus compared to NPH insulin in T2 diabetic patients.1, 13

Lantus better NPH Insulin betterDay-time hypoglycaemia

Total hypoglycaemia

Severe

Odds ratio

1 01 (0.49, 2.07), p=0.988

0.64 (0.39,1.04), p=0.073

0.88 (0.75, 1.04), p=0.1 36

0.74 (0.25, 2.23), p=0.494

0.51 (0.35, 0.76), p<0.0010.64 (0.46, 0.88), p=0.018

0.33 0.5 0.7 0.85 1.0 1.2 1.4 2.0 3.0

Symptomatic, PG <2.0 mmol l-1

Symptomatic, PG <3.9 mmol l-1

Severe

Symptomatic, PG <2.0 mmol l-1

Symptomatic, PG <3.9 mmol l-1

0.52 (0.27, 1.00), p=0.0498

0.44 (0.25, 0.76), p=0.003

0.52 (0.35, 0.76), p=0.009

Severe

Symptomatic, PG <2.0 mmol l-1

Symptomatic, PG <3.9 mmol l-1

Nocturnal hypoglycaemia

Adapted from Home et al, 2010. A meta-analysis of randomised controlled trials with accessible individual patient data and including white European people with Type 2 diabetes (T2DM) using glargine or NPH once daily (with oral glucose lowering drugs). Odds ratios (95% confidence intervals) for HbA1c – adjusted risk of hypoglycaemia for Lantus vs NPH insulin in pool 1 (evening glargine) for the different grades of severity and times of day.13

IndicationsLantus is an insulin analogue indicated for once-daily subcutaneous administration in the treatment of Type 1 or Type 2 diabetes mellitus patients who require insulin for the control of hyperglycaemia in patients 6 years and older.1

These results were generated from trials with different study designs, methodologies and patient groups. Only Lantus results are shown.

Dosage & AdministrationLantus is given subcutaneously once daily at the same time every day. Lantus is not intended for IV administration. Doses and timing of any antidiabetic medications, including Lantus must be determined and adjusted individually. In a clinical study with insulin naive T2DM patients the median starting dose of Lantus was 10 units. Close blood glucose monitoring is recommended. Injection sites must be rotated from one injection to the next. Lantus cannot be diluted or mixed with any other insulin or solution as this may change the time-action profile and may also cause precipitation.1

Starting insulin naive T2DM patients on LantusCommence Lantus 10 units morning or night - add it to the oral hypoglycaemic agents (OHAs)14

Next steps for newly started patients on LantusStep 1: Fix the fasting blood glucose - adjust the Lantus dose using one of the schedules below14, 15 to achieve RACGP target FBG of 4-6 mmol/L14

If fasting blood glucose level (FBG) is high pre-breakfast give —> Lantus at bedtime14

If FBG is on target but predinner blood glucose level (BGL) is high —> Lantus in the morning (instead of bedtime)14

Adapted from RACGP 2010/11 and Davies et al. 2005.* If for three days in a row, FBG> 6 mmol/L, increase the dose by 2 U.† Titration reviewed by healthcare professionals at each contact. Titrate only in the absence of BGL < 4mmol/L

Schedule 1 - Patient self titration.14, 15, † Schedule 2 - Physician managed titration14, 15

Adapted from Phillips 2007 and Davies et al. 2005.**The insulin dose may be decreased (small decrease of 2-4 units) if there is severe hypoglycaemia (requiring assistance) or the BGL < 3.0 mmol/L in the preceding week. Do not increase the insulin dose if the fasting BGL < 4.0 mmol/L at any time in the preceding week.

Mean FBG (mmol/L)

<4 Reduce by 2 to 4 units**

4-5.9 no change

6-6.9 + 2 units

7-7.9 + 4 units

8-10 + 6 units

>10 + 8 units

Increase by 2 units every 3 days*, continue until FBG < 6 mmol/L14, 15, †

After starting LantusAdjust the Lantus dose to achieve a FBG of 4-6 mmol/L. The mean FBG is calculated based on the FBG results for the last 3 days.14, 15

Step 2: Once FBG is on target, confirm the evening (or other) preprandial BGL is on target14

Step 3: Review A1c at 3 months14, 15

Consider stopping sulfonylurea and decreasing dose of metformin and/or glitazone14, 15, 16

Step 4: Find hidden hyperglycaemia (if A1c > 53mmol/mol)

If preprandial BGLs are on target but A1c and postprandial BGLs are not, review need for a dose of rapid-acting insulin to manage postprandial hyperglycaemia14

PrecautionsHypoglycaemia, possibly with delayed recovery or altered warning symptoms; hepatic, renal and visual impairment; lipodystrophy and other injection site or immediate-type allergic reactions; antibody production; patient instruction on intercurrent conditions, blood glucose monitoring, injection technique; not studied in children <6 years, pregnancy category B3, lactation; not intended for i.v. use; not recommended for treatment of diabetic ketoacidosis; LANTUS MUST NOT BE DILUTED OR MIXED WITH ANY OTHER INSULIN OR SOLUTION 1.

Adverse EventsThe most common adverse reactions associated with human insulin therapy include the following: allergic reactions, injection site reactions, hypoglycaemic and visual disturbances.1 Refer to the Data Sheet for further information associated with Lantus adverse effects 1.

PresentationLantus (insulin glargine injection) 100 units per ml (U 100) is available as a 10ml vial, 3ml cartridges for reusable insulin injection devices and 3 ml cartridges in SoloStar prefilled disposable devices.

Example: John currently takes 48 units of NPH at bedtime. John will take 48 units of Lantus at bedtime and titrate to achieve his target fasting blood glucose level (FBG.)

Example: Gillian currently takes 29 units of NPH in the morning and 15 units at bedtime. Her total NPH dose is 44 units per day. Gillian will now take 35 units (0.8 x 44 units) of Lantus at bedtime as a starting dose and titrate to achieve her target fasting blood glucose level (FBG).

Switching T2DM patients from other Isophane insulin therapies to Lantus®Isophane= Protaphane or Humulin NPH insulin

Recommendations for starting doses of Lantus when switching from Isophane1

#A guide to starting dose only. Dose should be determined individually and further titration may be required with close BGL monitoring. The amount and timing of short- or rapid-acting insulins will need to added/adjusted individually including the dose of any oral antidiabetic drugs.

Patients on NPH once daily 1 unit NPH: 1 unit Lantus (1:1)

Patients on NPH twice daily 1 unit NPH: 0.8 units Lantus (Use 80% of total NPH dose for Lantus dose)1

References 1. Lantus Data Sheet. 26 August 2010. 2. McKeage K, GoaKL. Treat Endocrinol 2002; 1(1):55-8. 3. Goykhman S, et al. Expert Opin Pharmacother 2009;10(4):705-18. 4. Lepore M et al. Diabetes 2000; 49:2142-2148. 5. Riddle et al. Diabetes Care 2003;26(11):3080-3086. 6. Bretzel R et al. Lancet 2008; 371:1073-84. 7. Janka H et al. Diabetes Care2005;28:254-259. 8. Rosenstock J et al. Diabetes Care 2006;29:554-9. 9. Buse J et al. Diabetes Care 2009;32:1007-1013. 10. Yki-Jarvinen H et al. Diabetologia 2006;49 (3):442-51. 11. Raskin P et al. Diabetes Care 2005; 28:260-5. Ligthelm R J et al. Endocr Pract 2010; 1-30. 13. Home et al. Diabetes, Obesity and Metabolism 2010, 12:772-779. 9. Davies et al. Diabetes Care 2005;28(6) 1282-1288. 14. Phillips PJ. Medicine Today 2007;8(3): 23-24. 15. Davies et al. Diabetes Research & Clinical Practice 2008;79:368-375. 16. Diabetes Australia/RACGP. Diabetes Management in General Practice. 2011/2012. 17. NZ Pharmaceutical Schedule. April 2013.

Lantus Abridged Data Sheet

Lantus® (insulin glargine). Indication: Once-daily subcutaneous administration for type 1 and type 2 diabetes mellitus patients who require insulin for control of hyperglycaemia. Contraindications: Hypersensitivity to insulin glargine or any excipient. Precautions: Hypoglycaemia, possibly with delayed recovery or altered warning symptoms; hepatic, renal and visual impairment; lipodystrophy and other injection site or immediate-type allergic reactions; antibody production; not studied in children <6 years, pregnancy category B3, lactation; not intended for i.v. use; not recommended for treatment of diabetic ketoacidosis; LANTUS® MUST NOT BE DILUTED OR MIXED WITH ANY OTHER INSULIN OR SOLUTION. Patient instruction on intercurrent conditions, blood glucose monitoring, injection technique recommended. Interactions: Oral antidiabetic agents; cardiovascular, analgesic, anti-inflammatory, neurological, antipsychotic agents, antibiotics, corticosteroids, other hormonal therapies, diuretics, protease inhibitors, sympathomimetic agents, lithium, alcohol, sympatholytics including -blockers, others. Adverse effects: Hypoglycaemia; injection site reactions; visual disturbances; others. Dosage and Administration: Subcutaneous, once daily; abdominal, thigh or deltoid administration; blood glucose monitoring is recommended. Lantus® is equipotent to human insulin. Initial dose should be determined individually, depending on desired blood glucose levels and doses and timing of any antidiabetic medication, including Lantus®. For changeover from once-daily NPH initial dose usually not changed; for changeover from twice-daily NPH to once-daily Lantus®, initial dose usually reduced by approximately 20% compared to total daily NPH dose; for initiation of type 2 patients, initial dose is usually approximately 10IU. For secondary dose adjustments, renal, hepatic impairment see full Data Sheet. Medicine Classification: Prescription Medicine. Presentations: Lantus® (insulin glargine injection) 100 U per mL is available in packs of 5x3mL cartridges, 5x3mL cartridges in SoloStar® pre-filled pens and 10mL vials. Sponsor: Sanofi, Level 8, James & Wells Tower, 56 Cawley Street, Ellerslie, Auckland. Lantus® is a Funded Medicine. TAPS PP3835, NZ GLA.13.05.001 May 2013.

Storage Unopened vials, cartridges and pre-filled pens (Lantus SoloStar) should be stored in a refrigerator (temperature: between +2°C and +8°C). Do not freeze. Discard if frozen. Before use, Lantus must be kept at room temperature for 1-2 hours. Lantus must only be used if the solution is clear, colourless with no particles visible and if it is of water-like consistency.

Open (in use) or unrefrigerated vials, cartridges and pre-filled pens must be discarded after 28 days from first use or removal from refrigeration as long as the temperature is not greater than 25°C and it is kept away from direct heat and light. Once in use, pre-filled pens or a reusable injection pen containing a cartridge of Lantus must not be stored in the refrigerator.1

ReimbursementAll Lantus presentations are fully funded for all Type 1 and Type 2 Diabetes Mellitus patients requiring insulin 17.