Insulins

Insulins

Insulins Roland Halil, BScPharm, ACPR, PharmD Clinical Pharmacist, Bruyere Academic Family Health Team Assistant Professor, Dept of Family Medicine, U of Ottawa March 2019 Insulin products New Drugs/Drug News vol 24 (3): May/J 2006 Insulins (contd) Long = Basal Short = Prandial NPH / Humulin N

Glargine (Lantus & Short Regular (Humulin R) Novolin ge Toronto Toujeo) Detemir (Levemir) Degludec (Trusiba) Rapid Premixed Lispro (Humalog) Aspart (NovoRapid)

Glulisine (Apidra) 30/70 (and 10/90, 20/80, 40/60, 50/50) Humalog Mix-25, NovoMix-30 Which to choose? Basic Concepts Hyperglycemia = Chronic Hypoglycemia = Acute So, go after Hypos first! Fed: 6h/24h = 25% Fasting: 18h/24h = 75% So, go after Fastings first! AM affects PM & HS

So, go after AM first! 1. ?Any hypos?- fix em! then, 2. FBS AM 3. FBS Noon 4. FBS PM 5. FBS HS then, 6. 2h PPG AM 7. 2h PPG Noon 8. 2h PPG PM Insulins (contd 2) Long Basal Short Prandial

NPH / Humulin N Glargine (Lantus & Short Regular (Humulin R) Novolin ge Toronto Toujeo) Detemir (Levemir) Degludec (Trusiba) Rapid Premixed

Lispro (Humalog) Aspart (NovoRapid) Glulisine (Apidra) 30/70 (and 10/90, 20/80, 40/60, 50/50) Humalog Mix-25, NovoMix-30 (R + NPH) (Rapid + NPH) Now, which to choose? Rational Prescribing FOUR steps to Rational Prescribing:

1. Benefit 2. Harm 3. Cost 4. Convenience Long Basal Insulins Benefit: NPH = glargine = detemir = degludec = NPH Equivalent Morbidity benefits, A1c lowering effect Despite the marketing: Kinetics dont affect overall efficacy: Slowest absorption: Thigh (best for basal insulins) Fastest absorption: Abdomen (best for prandial insulins) Lots of glargine is injected BID

NPH can be used QHS for some (esp. CKD) Long Basal Insulins (contd) Harm: All: Hypoglycemia NPH: Peak effect at ~ 8hrs (4-10hrs) Greater risk of hypoglycemia vs glargine Small difference Insulin analogues: Glargine / Detemir: Increased breast cancer risk? more research needed Degludec: too new - unknown 1. Lipska KJ, et al. Association of Initiation of Basal Insulin Analogs vs Neutral Protamine Hagedorn

Insulin With Hypoglycemia-Related Emergency Department Visits or Hospital Admissions and With Glycemic Control in Patients With Type 2 Diabetes . JAMA. 2018;320(1):5362. doi:10.1001/jama.2018.7993. https://jamanetwork.com/journals/jama/fullarticle/2685850 Accessed Mar 12/19 2. Rosenstock J, et al. Reduced risk of hypoglycemia with once-daily glargine versus twice-daily NPH and number needed to harm with NPH to demonstrate the risk of one additio nal hypoglycemic event in type 2 diabetes: Evidence from a long-term controlled trial Long Basal Insulins (contd 2) Cost: All: covered under ODB N.B. No Rx required for any insulins all OTC NPH: ~ $60 Lantus: ~ $115 Levemir: ~ $115 Degludec ~ $155 Convenience:

All sc injections, via penfills All QD BID Bottom Line Basal Insulins All equivalent Choose therapy based on cost (NPH) For the very small proportion suffering from hypoglycemia due to the peak effect of NPH or lamenting BID dosing, consider glargine or detemir. Starting Basal Insulin Fancy Way: calculate unit/kg dose = 0.1 - 0.2u/kg/day sc Risk hypoglycemia on first dose lose your patients buy-in forever.

Primary Care Method: Initiate 5u or 10u qhs sc Titrate by 1-2u q3-4d until AM FBS = 4 - 7 mmol/L 10% titrations If dose = 30s increase by 3 units If dose = 40s increase by 4 units etc. etc. Alternative: 1 unit every day till AM FBS = 4-7 mmol/L Rx 1. NPH Sig: 10u qhs sc or ud M: 1 box penfills Repeat x 12 2. Needle tips 28G - 6mm

Sig: ud M: 1 box r x 12 N.B. (Please teach pt pen technique) Insulin Long = Basal Short = Prandial NPH / Humulin N Glargine (Lantus &

Short Regular (Humulin R) Novolin ge Toronto Toujeo) Detemir (Levemir) Degludec (Trusiba) Rapid Premixed Lispro (Humalog) Aspart (NovoRapid) Glulisine (Apidra)

30/70 (and 10/90, 20/80, 40/60, 50/50) Humalog Mix-25, NovoMix-30 (R + NPH) (Rapid + NPH) Short Prandial Insulins Efficacy Equivalent reduction in morbidity, HgbA1c Short Prandial Insulins (contd) Toxicity Hypoglycemia Rapid insulins better reflect physiological effect

of pancreatic insulin (vs Regular insulin) More important in CKD (=longer insulin t ) Short Prandial Insulins (contd 2) Cost All covered under ODB Regular (R) / Toronto ~ $40 NovoRapid (aspart) ~ $56

Humalog (lispro) ~ $55 Apidra (glulisine) ~ $48 Convenience All injected with meals Regular insulin injected 30-45 min before meal Rapid insulin can be taken with meal Reduced risk of hypo if pt injects, then forgets to eat Bottom Line Prandial Insulins All equivalent Choose therapy based on cost / familiarity Rapid insulins reflect pancreatic insulin release better than [R]/Toronto. The worse the CrCL, the more important this fact becomes.

Starting Prandial Insulin Fancy Way: Total dose: 0.5u/kg 40% of total dose - basal insulin qHS 20% of total dose TID with meals (60%) prandial insulin 1530 min before meals Eg. 80kg pt 0.5u/kg = 16u basal (40%); 8u TID (20% x 3 = 60%) Primary Care Method: Start 5u sc with meals Titrate AM to HS to target Monitor 2h PPG Start injection TID or only single meal as required If poor control: inj TID sc; If mediocre control: inj qAM sc Still aim for ~ 2/3rds split (40% basal / 60% prandial)

Insulins (contd 3) Long = Basal Short = Prandial NPH, (N) Glargine (Lantus) Detemir (Levemir) Short Regular (R) Toronto Rapid Premixed

Lispro (Humalog) Aspart (NovoRapid) Glulisine (Apidra) 30/70 (and 10/90, 20/80, 40/60, 50/50) (Reg + NPH) Humalog Mix-25, NovoMix-30 (Rapid + NPH) Pre-mixed Insulins NovoMix-30 = Humalog Mix25 (equivalent) Efficacy All ~ 30% short / 70% long Toxicity Hypoglycemia (less with Rapid vs Regular insulin)

Cost: ~$53 (Rapids) ~$40 (Regular 30/70) Convenience ~ Rapids can be injected with meal Starting Pre-mixed Insulins Fancy Way: Estimate total starting daily dose (0.3-0.6 units/kg) Divide daily dose: 2/3 before breakfast; 1/3 before supper Primary Care Method: From scratch: Start 5-10u QD-BID and titrate From other insulins: Calculate approximate amount of basal and prandial units and divide 2/3rd - 1/3rd AM and PM

Pearls Insulin is 2nd line after metformin No need to save it for last! Better than adding a 3rd PO drug Better efficacy, lower toxicity, better studied Improve buy-in from patient: Natural supplement Only BID glucochecking at alternating times required:

Pre-Breakfast + Post-Breakfast, then Pre-Breakfast + Pre-Lunch, then Pre-Breakfast + Post-Lunch, then Pre-Breakfast + Pre-Supper, then Pre-Breakfast + Post-Supper, then Pre-Breakfast + Pre-Bedtime Repeat Pearls (contd) D/C secretagogues after starting insulin to reduce risk of hypos. Eg. Sulfonylureas, meglitinides Black box warning against combo with glitizones! (Actos, Avandia)

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