INFORMATION ON USE OF GLARGINE IN DIABETIC CATS
Using Glargine In Diabetic Cats (June 2006)

Rhett Marshall BVSc MACVSc1,2,
Jacquie Rand BVSc DVSc Dip ACVIM1
1Centre for Companion Animal Health, School of Veterinary Science,
The University of Queensland and
2Creek Road Cat Clinic, Brisbane, Australia.

These instructions for using glargine are based on a relatively small number of cats, and caution should be exercised with the insulin until it has been used in an extensive number of cats. Because glargine is very long-acting, there is the potential for prolonged hypoglycemia if overdosed.

BASIC INFORMATION


Glargine (Lantus) is readily available from most pharmacies with a script, is not licensed for use in cats.
Glargine must not be diluted or mixed with anything because the prolonged action is dependent on its pH.
Insulin glargine should be kept refrigerated to prolong its life.
Insulin glargine has a shelf-life of 4 weeks once opened and kept at room temperature. Opened vials stored in the refrigerator can be used for up to 6 months.
Discard vial immediately if there is any discolouration. Bacterial contamination and precipitation associated with pH change can cause cloudiness.
If using an insulin pen, the manufacturer recommends that the pen and cartridge be kept at room temperature and not refrigerated. This is to reduce the changes in volume of insulin dispensed associated with changes in temperature.
When performing a blood glucose curve, samples probably only need to be taken every 4 hrs over 12 hrs in many cats (ie. 0h [before morning insulin], 4h, 8h and 12h after morning insulin).
Dose changes should be made based on pre-insulin glucose concentration, nadir (lowest) glucose concentration, daily water drunk, and urine glucose concentration.
Better glycemic control is achieved with twice daily dosing rather than once daily.

Some pharmacies stock insulin syringes (Wal-Mart) with gradations in ¼ U, which are ideal for cats.
Some cats that have been treated with other insulin will go into remission, usually within 1-4 months after instituting Glargine. Remission in cats that have been treated for more than 2 years is extremely rare.
Remission is likely to occur if the nadir glucose is in the normal range and pre-insulin blood glucose is less than 216 mg/dL (12 mmol/l). However, for some cats to achieve remission, the dose needs to be very gradually reduced, tapering off to ½ U SID before being withdrawn. Too rapid withdrawal often requires restabilizing at a higher dose for some weeks.
INDICATIONS FOR USING GLARGINE

All newly diagnosed diabetic cats (to increase chance of remission).
Poor controlled or unstable diabetic cats (glargine's long duration of action is likely to benefit these cats).
When SID dosing is desired or demanded (it is important to note that better glycemic control and higher remission rates will be obtained with BID dosing. SID dosing only provides similar control and remission rates to lente BID).
Ketoacidosis - combined with regular insulin IM or IV.
When corticosteroid administration is required in cats in remission. Similarly in cats at high risk of developing clinical signs of diabetes with corticosteroid administration.
STARTING CATS ON GLARINE

If blood glucose conc. > 360mg/dL (20mmol/L) begin glargine at an initial dose of 0.5U/kg ideal body weight twice daily (BID)
If blood glucose conc < 360mg/dL (20mmol/L) begin at 0.25U/kg ideal body weight BID
Perform a 12hr glucose curve with samples taken every 4hrs
DO NOT increase dose for the first week
Decrease dose if biochemical or clinical hypoglycemia occurs
It is suggested that cats stay in hospital for 3 days to check the initial response to insulin, or home glucose curves are obtained for the first 3 days
Recheck at 1, 2, 3 and 4 weeks after the cat is sent home, and then as required
Many cats have negligible glucose lowering effect in the first 3 days (do not increase dose), although by day 10 after beginning insulin, most cats have good glycemic control
Ketoacidotic cats may be treated with glargine s/c at the above dose rates in combination with regular insulin IM or IV (we have found IU regular insulin IM every 2-4 hours based on glucose conc works best). This regime is continued until hydration restored and appetite reteurns, which usually occurs in 1-3 days.
ADJUSTING TO INSULIN DOSE

1. Indications for increasing dose of glargine

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If pre-insulin glucose conc. is >216mg/dL (12mmol/L), then increase dose by 0.25-1 U/injection depending on the degree of hyperglycemia.
AND / OR
If nadir (lowest) glucose conc. is >180mg/dL (>10mmol/L) then increase dose by 0.5-1 U/injection.
For well controlled cats after several weeks of therapy, increase dose if nadir is more than or equal to 8 mmol/L (145 mg/dl).

2. Indications for maintaining the same dose

If pre-insulin glucose conc. >180 - <216 mg/dL (>10 - <12mmol/L)
AND / OR
If nadir glucose conc. 90-160mg/dL (5-9mol/L).
For well controlled cats after several weeks of therapy, aim for a nadir of 72 -145 mg/dL (4-8 mmol/L)

3. Indications for decreasing dose of glargine

If pre-insulin glucose conc <180mg/dL (<10 mmol/l) decrease 0.5 - 1U
If nadir glucose conc < 54mg/dL (<3 mmol/l) decrease 1U
If clinical signs of hypoglycemia develop, administer 50% glucose IV bolus followed by 2.5% glucose infusion, then reduce dose by 50% and check for remission.
If clinical hypoglycemia develops and is not severe, it can often be managed by feeding the cat, preferably a higher carbohydrate containing food, such as a some dry foods. However, it must be palatable enough to eat. Most weight reducing and renal diets are high carbohydrate diets, as are many grocery lines of dry food.
For cats with unexpected biochemical hypoglycemia (not clinical signs), some owners find that they can manage the hypoglycemia by delaying the insulin injection until blood glucose increases to 10 mmol/l (180 mg/dL) and then give the same dose (the following dose of insulin may need to be reduced), while others find it best to reduce the dose once glucose is 10 mmol/l (180 mg/dL), although this may result in subsequent hyperglycemia.

4. Insulin dose may be maintained, increased or decreased depending on the water intake, urine glucose, clinical signs and length of time the cat has been treated with insulin

If pre-insulin glucose conc. 198 - 252 mg/dL (11 - 14 mmol/L), or if nadir 54 - 72 mg/dL (3 - 4 mmol/l), clinical parameters are essential for adjustment of insulin dose.
DETERMINING IF THE CATS IS IN REMISSION

Insulin dose should be

gradually reduced by ¼-1 U/cat/injection if nadir blood glucose is in the normal range of (72 -126 mg/dL; 4-7 mmol/L) or either pre-insulin glucose concentration is < 10 mmol/L. Slow withdrawal of insulin is advocated until dose is ½ - 1 U once daily (SID).
After a minimum of 2 weeks of insulin therapy, if the pre-insulin blood glucose is < <180mg/dL (<10mmol/L) and insulin dose is ½-1 U SID, insulin should be withheld and a 12hr glucose curve performed. If at the next due dosing time the blood glucose is >200mg/dL (12mmol/L), then insulin can be administered at 1U BID and then gradually reduced as indicated. If blood glucose is <200mg/dL then continue to withhold insulin and discharge with a follow-up visit in 1 week. Water intake and urine glucose should be closely monitored and insulin reinstituted if glycosuria returns or water intake increases.
Some cats may have a pre-insulin glucose concentration below 10mmol/L (180 mg/dL) within 2 weeks, but insulin therapy should be maintained for a total of 2 weeks to give beta cells a better chance at recovery from glucose toxicity. Use 0.5-1U BID or once daily until insulin is withdrawn

URINE GLUCOSE

With the long duration of action of glargine, there should be minimal periods when blood glucose is >14mmol/L (240mg/dL) for cats treated for more than 2 to 3 weeks, and hence well controlled cats should almost always be 0 or 1+ for urine glucose. A value 2+ or greater likely indicates that an increase in dose is required.

OTHER OBSERVATIONS FROM USING GLARGINE

For some cats, the dose needs to be increased to 5 or 6 U/cat BID, but can then usually be reduced as insulin sensitivity returns. Cats on these high doses need to be carefully monitored for hypoglycemia.
Some cats require only small doses of insulin (<1 U/cat BID) and only go into remission if the dose is reduced very slowly giving few remaining beta cells a chance to recover.

For many cats, the time at which the nadir (lowest) glucose concentration occurs is often not consistent from day to day, or between cats. Sometimes it occurs somewhere between the two doses, but sometimes the nadir occurs around the time of the next dose.
Most commonly the highest glucose concentrations occur in the morning and the lowest in the evening.
Some cats consistently have their nadir glucose concentration in the evening just before the next insulin injection, and less commonly, it occurs around the time of their morning injection.
To increase the chance of remission, we suggest aiming for perfect control or possibly slightly overdosing during the first 2 months, provided the veterinarian and owner can carefully monitor the cat. There is the potential risk of hypoglycemia, but we believe this is outweighed by the benefit of diabetic remission to the cat and owner.
Cats requiring intermittent or chronic corticosteriod administration that are either in remission or at risk of developing diabetes can usually safely be placed on IU SID or BID.
It is a very common observation by owners that when long-term stable diabetic cats are changed over to glargine, usually they do better clinically, even if blood glucose results do not support the clinical improvement.
More information on glargine and general information

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