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LIFE AFTER LENTE: CHOOSING FROM AVAILABLE INSULINS Stacey B. Hoffman, DACVIM September 21, 2005

LIFE AFTER LENTE: CHOOSING FROM AVAILABLE INSULINS Stacey B. Hoffman, DACVIM September 21, 2005. Origins of insulins. Historically, beef, pork, or beef/pork origins Pork insulin identical to canine insulin Beef insulin one amino acid away from feline insulin

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LIFE AFTER LENTE: CHOOSING FROM AVAILABLE INSULINS Stacey B. Hoffman, DACVIM September 21, 2005

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  1. LIFE AFTER LENTE:CHOOSING FROM AVAILABLE INSULINSStacey B. Hoffman, DACVIMSeptember 21, 2005

  2. Origins of insulins • Historically, beef, pork, or beef/pork origins • Pork insulinidentical to canine insulin • Beefinsulinone amino acid away from feline insulin • More recently, human recombinant insulins available: one amino acid away from canine insulin, less similar to feline

  3. Duration of action • Short acting: semilente (available only in mixtures) and regular • Intermediate acting: NPH (protamine to retard absorption) and lente (combination of semilente and ultralente) • Long acting: PZI (protamine zinc insulin) and ultralente

  4. Upcoming changes • Eli Lilly discontinuing manufacture of Humulin L(lente) and Humulin U(ultralente)-Dec. 2005 • New insulins to consider: Vetsulin (just approved in US 2005), PZI (commercially manufactured by IDEXX), glargine (new human insulin product)

  5. Insulin pharmacokinetics:dogs(Stenner et al, 2004 ACVIM Forum, p. 866) • Comparison of PZI, porcine lente, glargine in healthy dogs • Dose: 0.5 U/kg SQ • Triple cross-over study

  6. Canine pharmacokinetics

  7. Study results • Lente insulin: predictable insulin peak with shorter onset & duration of action than PZI • PZI: lowers blood glucose with a prolonged duration of action in all dogs • Glargine: 2/9 dogs did not have significant lowering of blood glucose after glargine, unpredictable insulin concentration response in other dogs

  8. Lente insulins • Human recombinant Humulin L (E. Lilly) off market, new pork product (Vetsulin) available • Absorption controlled by size of zinc insulin crystals • Semilente (30%): small crystals, prompt absorption • Ultralente (70%): large crystals, extended absorption

  9. Vetsulin® insulin • U-40 insulin, porcine origin • Available in Canada as Caninsulin ®, now FDA approved in United States • Website: www.vetsulin.com • Lente insulin: 30% amorphous insulin (rapid onset), 70% crystalline zinc insulin (longer duration) two peaks

  10. Manufacturer’s dose

  11. Vetsulin study • 53 client owned dogs, 34% controlled with SID dosing and 66% BID • Manufacturer’s recommendation for starting dose-1 U/kg plus dose supplementation given once daily at meal times • If changing to Vetsulin BID from human lente or NPH, recommend decreasing dose by 25% (or 50% if changing to Vetsulin SID)

  12. Insulin therapy diabetic dogs(Hess, ACVIM Forum 2001) • >50% of diabetic dogs in retrospective study received insulin injections SID (NPH, lente) • At time of clinical control, only 6% (5/83) received SID insulin • SID insulin administration in dogs associated with inadequate glycemic control, insulin overdose, hypoglycemia • Recommend starting lente (Vetsulin) 0.5 U/kg BID diabetic dogs

  13. Vetsulin(Source: Intervet-manufacturer) • How much $$$ to treat 40 lb dog? • Once daily • Twice daily • Should owner use 2.5 ml or 10 ml vial? • How long will insulin vial last?

  14. Vetsulin(Source: Intervet-manufacturer) • Cost per ml • 10 ml • 10 ml/vial x 40 U/ml = 400 units per vial • $30/vial (~pet owner cost) • $30/vial ÷ 400 units/vial • 7.5 cents per unit • 2.5 ml • 2.5 ml/vial x 40 U/ml = 100 units per vials • 10 vials per box • $42.80 ÷ 10 vials = $4.28 x 2 + round-up = $8.75 (to ō) • $8.75/vial ÷ 100 U/vial = 8.8 cents per unit

  15. Vetsulin(Source: Intervet-manufacturer) • Cost per syringe • $19.90 vet cost per box • ~$25.00 pet owner cost per box • 100 syringes per box • $25 ÷ 100 = 25 cents per syringe

  16. Vetsulin (Source: Intervet-manufacturer) • How long will a 10 ml vial last for this dog? • How many units per 10 ml vial? 40 U/ml x 10 ml = 400 U 400 U ÷ 21 U/day = 19 days

  17. Vetsulin cost for 40 lb dog(Source: Intervet-manufacturer) • What is the dosage and the dose? • For once daily: 40 lb ÷ 2.2 lb/kg = 18.18 kg 18 kg x 1U/kg = 18 U Plus 3 U (wt-based dose supplement) Total of 21 units per day • Cost of Vetsulin (10 ml) is 7.5 cts/U • 7.5 cts/U x 21 units = $ 1.58 per day • Cost of syringe is 22 cents each • Total cost per day is $1.80 per day for 40 lb SID

  18. Vetsulin(Source:Intervet-manufacturer) • What is the dosage? • For twice daily: Decrease dose by 25% Previously 21 units 21 x .75 = 15.75 New dose is 15 units, 2 times a day Therefore 30 units per day • Total cost • Vetsulin: 30 units per day x 7.5 cts/unit = $2.25 • Syringes: 44 cts per day for 2 syringes • Total = $2.69 per day

  19. Insulin glargine (Lantus) • New synthetic (recombinant) human insulin analogue • Clear solution with pH 4.0, microprecipitates form when acidic insulin interacts with neutral pH subcutaneous tissues following injection • In human medicine, considered long-lasting “peakless” insulin

  20. Pharmacokinetics study-cats(Rand and Marshall, 2005 ACVIM Forum) • Triple blind cross-over study in normal cats, comparing PZI, glargine, and pork lente • All cats dosed at 0.5 U/kg SQ • No difference between insulin types w.r.t. onset of action and glucose nadir values • In contrast to results in humans, glargine is not “peakless” in cats

  21. Feline pharmacokinetics

  22. Glargine in diabetic cats(Rand and Marshall, 2005 ACVIM, p.483) • 24 newly diagnosed diabetic cats, all fed Purina DM (low carb-high protein) • Received either PZI, porcine lente, glargine (0.25 or 0.5 U/kg BID) • 8/8 glargine cats achieved diabetic remission within 4 months (reversal of glucose toxicity of ß cells), mean remission 13 +/-3 mos. • 5/16 PZI/lente cats remission

  23. Glargine vs. lente(Weaver et al, 2005 ACVIM Forum, p. 863) • Both newly diagnosed and poorly controlled diabetic cats (13 total), all fed Purina DM • Starting doses: lente 0.5 U/kg BID or glargine 0.5 U/kg SID • No difference between groups w.r.t. treatment response or remission rates • 4/13 cats achieved complete remission

  24. Glargine information • Although 0.5 U/kg SID has significant glucose lowering effect, 0.25 U/kg BID has longer effect • Better glycemic control with BID dosing • In clinical study (Rand and Marshall), no diabetics on glargine showed clinical hypoglycemia despite low glucose values • Starting dose: 0.5 U/kg BID, most cats need dose reduction within 2 wks, remission 4 wks

  25. PZI insulin • Beef (90%)/pork (10%) origin insulin with longer duration of action • Comes as U-40 insulin, so need to use U-40 insulin syringes (will underdose 2.5X if using U-100 syringes) • Commercially available from IDEXX

  26. PZI in diabetic cats(Nelson et al 2001, JAVMA 218(1): 38-42) • Starting doses of PZI: 0.2-0.6 U/kg BID • Clinical signs of hypoglycemia in 5/67 cats, others hypoglycemic w/o signs • Overlap between doses that cause hypoglycemia, control glycemia, don’t control blood glucose • Recommend starting doses of PZI low (1 U/injection)

  27. SID vs. BID PZI • Historically, PZI often been administered to cats once daily (pharmacokinetic data?) • Variations in PZI absorption: blood glucose nadir 1-12 hours post injection, return to baseline 8-24 hours post injection • Could consider once daily PZI in cats that reach nadir > 10 hours post insulin, but most cats (75%) need BID dosing

  28. Treatment options: cats • Insulin glargine: may be best choice in newly diagnosed diabetics, possible remission w/diet • NPH insulin (Humulin or Novolin) • Lente insulin (Vetsulin): starting doses of 0.25-0.5 U/kg BID (short duration of action, anectdotal report) • PZI insulin: start low, BID dosing for most

  29. Treatment options: dogs • Humulin or Novolin NPH • Lente insulin (Vetsulin): use as if using Humulin L, rather than manufacturer’s instructions • PZI: rarely used in dogs • Glargine: unpredictable concentrations, fails to lower glucose in some dogs so probably a poor choice

  30. A few final points • Remember to use U-40 syringes with U-40 insulins (Vetsulin, PZI) • When changing between types of insulin, need reduce dose • Benefits of Purina DM diet in diabetic cats (low carb/high protein) • Clinical judgement (owner and DVM) will still play important role in regulation of diabetics

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