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Update on Insulin Glargine use in Diabetic Cats

Geplaatst: 26 nov 2006, 22:52
door Jeanne
Bron: Centre for Companion Animal Health, School of Veterinary Science, The University of Queensland 4072, Creek Road Cat Clinic, 189 Creek Road, Mt Gravatt 4122 Australia

Update on Insulin Glargine use in Diabetic Cats

Jacquie Rand BVSc DVSc Dip ACVIM*, Rhett Marshall BVSc, MACVS*#,

*Centre for Companion Animal Health, School of Veterinary Science,

The University of Queensland 4072, Creek Road Cat Clinic, 189 Creek Road, Mt Gravatt 4122 Australia

Glargine is a new human synthetic insulin analogue produced by recombinant DNA technology utilizing E.Coli. It differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the B-chain terminus. Glargine is a clear aqueous solution in 100U/ml vials with pH=4 until injected subcutaneously. The interaction of the acidic insulin and the relatively neutral pH of the subcutaneous tissues forms micro-precipitates, and has a relatively constant systemic absorption profile. The formation of micro-precipitates and slow absorption are dependant on the acidity of glargine, hence glargine cannot be mixed or diluted.

Glargine is

marketed for human patients as a very long-acting “peak less” insulin, with regard to its glucose lowering effects. It is designed to provide a basal or background insulin concentration, with the intention that a shorter-acting insulin be administered at meal times to achieve optimal glycemic control. Insulin glargine gained approval from the United States Food and Drug Administration in June 2000, for use in treating type 1 and type 2 diabetes in humans. The expected benefits in diabetic cats of an insulin preparation with a longer duration of action include improved glycemic control resulting in increased rates of diabetic remission, reduced rates of euthanasia, and decreased cost to clients.

The pharmacokinetics and pharmacodynamics of once daily administration of glargine compared with two of the most commonly used insulin preparations, porcine lente and protamine zinc insulin (PZI), has been reported in healthy cats.1 Once daily administration of glargine was found to have a similar mean daily glucose concentration and area under the 24hr glucose curve to PZI, and both were significantly lower than lente insulin. Glargine produced a glucose nadir later than PZI or lente, and had longer duration of action than lente. The duration of action for glargine was 23+0.9hrs, and 7 of the 9 cats had significantly decreased blood glucose concentration at 24hrs.1

The administration of glargine once daily versus twice daily has also been compared in healthy cats.2 While once daily administration of insulin glargine at 0.5U/kg provided a significant blood glucose lowering effect, a longer effect was achieved by administering glargine at 0.25U/kg BID. When using glargine in diabetic cats, we have found that most cats may be maintained on once daily injections of glargine, but superior glycemic control is achieved if insulin is injected twice daily. This is of particular importance in newly diagnosed cats in which prompt good glycemic control may result in remission, hence the recommendation for BID dosing in new diabetic cats.

The first reported use of glargine in a diabetic cat was in a female Burmese cat where it was used to successfully resolve urinary candidiasis.3 Prior to using glargine, this cat had been treated unsuccessfully with other insulins and fluconazole for 10 weeks and then changed to glargine as a single therapy. The good glycemic control achieved with the long-acting glargine changed the microenvironment in the urinary bladder and the infection resolved within 2 weeks, without concurrent antifugal therapy.3

The usefulness of glargine for treating newly diagnosed diabetic cats has been evaluated and is presented in an abstract at this forum5. Twenty-four newly diagnosed diabetic cats (17m,7f) were treated with either glargine, PZI or lente (n=8 for each group) and fed a very low carbohydrate-high protein diet (Purina DM canned). Insulin was initially given at 0.5U/kg BID S/C if blood glucose was >360mg/dl, and 0.25U/kg BID S/C if blood glucose was <360mg/dl. Insulin dose was then adjusted based on serial blood glucose curves and water intake. Cats were defined as achieving diabetic remission if normoglycemia was maintained without insulin therapy for more than 2 weeks.

At diagnosis, there was no statistical difference between treatment groups for age, body weight, body condition score, or concentrations of fructosamine, blood glucose, B-hydroxybutyrate or bicarbonate. Four of 8 cats in each group were Burmese5.

There was a non-significant trend for glargine treated cats to have lower 12hr glucose concentrations after 10 and 17 days, than those treated with PZI or lente 5. Mean 12hr blood glucose at 4 weeks was significantly lower for glargine than PZI and lente treated cats. Fructosamine concentration after 4 weeks of treatment was significantly lower than at diagnosis for glargine treated cats but not for PZI or lente5.

All 8 cats treated with glargine went into diabetic remission within 4 months of beginning treatment, while 3 cats treated with PZI and 2 cats treated with lente achieved diabetic remission5. Of the seven glargine treated cats alive, six cats remain in remission at the time of publication (mean remission time=13+3.5 months) 5. One of the remaining two cats alive treated with PZI (mean remission time=8.3+3.3 months) and both cats treated with lente (mean remission time=8+2 months) remain in remission5.

Only 1 cat treated with glargine required an increase in insulin dose above 0.5U/kg BID, and 7 of 8 cats had their insulin dose reduced in the first 3 days of treatment. This is an important factor when initiating treatment with glargine, as there is usually a carry-over effect from the previous dose that may take several days to become apparent.

A significant finding in this trial was that no cat treated with glargine showed clinical hypoglycemia despite having biochemical hypoglycemia, while 2 cats treated with lente and 1 cat treated with PZI insulin exhibited signs of clinical hypoglycemia.

Glargine can be safely instituted at 0.5U/kg bid and serial blood glucose curves should be obtained daily for 3 days either in hospital or at home. When evaluating the blood glucose curve using glargine, it is often more useful to assess pre-insulin glucose concentration rather than the nadir glucose. We have found it often takes 3-5 days for a good glucose-lowering effect to be seen in the glucose curves, possibly because of the long duration of action and carry-over effect of glargine. Almost all cats will need to have their initial dose reduced within 2 weeks and many will achieve remission within 4 weeks 5

Monitoring and adjusting insulin dose when using glargine should be based on a number of parameters including; pre-insulin and nadir glucose conc, water intake, urine glucose concentration and clinical assessment as shown in Table 1. We have found pre-insulin glucose concentrations measured at home an excellent tool for well-educated owners to safely modify daily doses of glargine. Cats treated with glargine should have a negative, 1+ or 2+ urine glucose (scale 0-4+) and a value of 3+ or 4+ likely indicates that a dose increase is required.

The good glycemic control when using glargine likely reverses glucose toxicity of the B-cells, which facilitates endogenous insulin production and a reduced requirement for exogenous administration. Insulin dose may be reduced sequentially as indicated by blood glucose concentration, urine glucose and water intake until the dose is 1U SID. Even if normoglycemic, it is recommended that insulin is not withdrawn within 2 weeks of commencent of therapy. Sequential deduction of insulin dose to 1 U SID is recommended before insulin is withdrawn, and the cat carefully monitored afterwards to ensure remission has continued. It is also imperative that cats remain on a low-carbohydrate diet with calorie control to prolong the remission period. It is the authors’ experience that newly diagnosed diabetic cats that have good glycemic control within the first few weeks of therapy, are very likely to go into diabetic remission. Cats that have been long-term diabetics are less likely to go into remission probably because of progressive B-cell loss.

It is the authors’ conclusion that glargine is safe and effective in treating feline diabetes and should be the preferred insulin in newly diagnosed diabetic cats. Long-term diabetic cats should be changed to glargine if there is poor glycemic control or owners wish to pursue once daily injections. High remission rates are expected in newly diagnosed cats when combined with a low-carbohydrate diet.

Table 1. Parameters for changing insulin doseage when using insulin glargine in diabetic cats.

Parameter used for doseage adjustment
Change in dose

If pre-insulin blood glucose concentration >360mg/dL (>20mmol/L)


If nadir blood glucose concentration >180mg/dL (>10mmol/L)
Increase by 0.5U

If pre-insulin blood glucose concentration 240<360mg/dL (15<20mmol/L)


nadir blood glucose concentration is 90-180mg/dL (5-10mmol/L)
Same dose

If pre-insulin blood glucose concentration is 198-252mg/dL(11-14mmol/L).

If nadir glucose concentration is 54-72 mg/dL (3-4 mmol/L).
Use nadir glucose, water drunk, urine glucose and next pre-insulin glucose concentration to determine if insulin dose is decreased or maintained.

If pre-insulin blood glucose concentration <180mg/dL (10 mmol/l)


If nadir blood glucose concentration < 54mg/dL (<3 mmol/l)
Reduce by 0.5- 1UU or if total dose is 0.5-1U SID, stop insulin and check for diabetic remission.

If clinical signs of hypoglycemia are observed
Reduce by 50%

If water intake is <20mls/kg on wet food or <70mls/kg on dry food
Same dose

If water intake is >40mls/kg on wet food or >100mls/kg on dry food
Increase dose by 0.5-1U

If urine glucose is > 3+ (scale 0 - 4+)
Increase dose by 0.5-1U

If urine glucose is negative
Check for diabetic remission

KEYWORDS: glargine, feline diabetes, diabetic remission, insulin


1.Marshall RD, Rand JS. Comparison of the pharmacokinetics and pharmacodynamics of glargine, protamine zinc and porcine lente insulins in normal cats, Journal of Veterinary Internal Medicine 2002, 16(3):358.

2.Marshall RD, Rand JS. Comparison of the pharmacokinetics and pharmacodynamics of once versus twice daily administration of insulin glargine in normal cats, Journal of Veterinary Internal Medicine 2002, 16(3):373.

3. Marshall RD, Rand JS, Gunew MN. Successful resolution of urinary candidiasis in a diabetic cat following treatment with insulin glargine, Journal of Veterinary Internal Medicine 2002, 16(3):373.

4. Marshall RD and Rand JS. Insulin glargine and a high protein-low carbohydrate diet are associated with high remission rates in newly diagnosed diabetic cats . Journal of Veterinary Internal Medicine 2004.

5. Marshall RD and Rand JS. Treatment with glargine results in higher remission rates than lente or protamine zinc insulins in newly diagnosed diabetic cats.Proceedings 24th ACVIM Forum 2005.

Geplaatst: 28 nov 2006, 06:58
door diana en tijger
Tip: voor mensen die de begrippen Bid en Sid niet kennen!:
Bid = 2 x per dag
Sid = 1 x per dag

Geplaatst: 28 nov 2006, 06:59
door diana en tijger
Oh ja Jeanne er is trouwens alweer een nieuwe update van dit onderzoek!Als ik er tijd voor heb zal ik het even opzoeken.Heb hem wel al gelezen,maar was in het Duits!

Geplaatst: 28 nov 2006, 08:58
door Jeanne
Oh dat is hartstikke mooi Diana, dan plaats je het hier ook maar bij Humane insuline - Nieuw onderwerp.