Transcript tresiba
Tresiba - insulin degludec Manufacturer: Novo Nordisk FDA Approval Date: 9/25/2015 Tresiba® - insulin degludec Objectives • At the end of this presentation participants will be able to: 1. Appropriately recommend Tresiba®- insulin degludec 2. Effectively educate patients on the purpose, proper use and potential adverse effects of Tresiba®- insulin degludec Tresiba® - insulin degludec Clinical Application • Indications: • Glycemic control in diabetes • Types I and II • Place in therapy: • Similar to that of Lantus or Levemir • Long-acting basal insulin Tresiba® [package insert]. Tresiba® - insulin degludec Clinical Application • Contraindications: • Hypersensitivity to insulin products • Use in DKA • Use during hypoglycemia • Warnings/precautions: • Hypoglycemia • Hypokalemia Tresiba® [package insert]. Tresiba® - insulin degludec Clinical Application • Pregnancy: • Category C • No studies in pregnant women • Weigh risk/benefit of using during pregnancy • Lactation: • Unknown if excreted in breastmilk • Endogenous insulin is excreted in breastmilk, so mothers may require adjustments in insulin or meal plan when breastfeeding Tresiba®[package insert]. Tresiba® - insulin degludec Drug Facts • Pharmacology: • Insulin is an endogenous peptide hormone • Stimulates cellular glucose uptake and utilization • Insulin degludec arranges into hexamers after subcutaneous injection that allow it to form a depot Tresiba®[package insert]. Tresiba® - insulin degludec Drug Facts • Pharmacokinetics: A Tmax ~ 9 hours D Protein binding >99% M No clinically relevant Hepatic/Renal metabolism, cleared by uptake into cells E T ½: 25hrs, duration of action: 42hrs Tresiba®[package insert]. Tresiba® - insulin degludec Drug Interactions • No direct drug-drug interactions • Consider drugs which may alter blood glucose levels or mask/blunt symptoms of hypoglycemia • Sulfonylureas, SGLT2s • Corticosteroids, thiazide diuretics • β-blockers, clonidine Tresiba®[package insert]. Tresiba® - insulin degludec Adverse Effects Tresiba insulin degludec Lantusinsulin glargine Hypoglycemia 81% 82% Nasopharyngitis 14% 14% Upper respiratory tract infection 14% 13% Headache 9% 7% Arthralgia 4% 8% Diarrhea 6% 8% *over 1 year of treatment Tresiba®[package insert]. Tresiba® - insulin degludec Monitoring Parameters • Efficacy Monitoring: • Blood glucose- daily (fasting, meals) • A1c- every 3 months • Toxicity Monitoring: • Blood glucose Tresiba®[package insert]. Tresiba® - insulin degludec Prescription Information • Dosing: • T1DM: ⅓- ½ daily insulin requirement, given once daily (generally daily requirement is 0.2-0.4 Units/kg in insulinnaïve patients • T2DM: Starting dose ~ 10 units once daily • Cost: pricing not determined, will be available Q1 2016 as a 3mL Flextouch pen. Tresiba®[package insert]. Tresiba® - insulin degludec Literature Review BEGIN Basal-bolus Type II • Purpose: compare insulin degludec to insulin glargine in efficacy and adverse effect profile • Design: Phase III, randomized, open- label, treat-to-target trial Garber A, et al. Lancet. 2012; 379:1498–507. Tresiba® - insulin degludec Literature Review • Primary endpoint: change from baseline in HbA1c concentration after 52 weeks • Secondary endpoints: change in fasting plasma glucose from baseline, percentage of patients reaching A1c goal of <7% • Safety assessment: hypoglycemia Garber A, et al. Lancet. 2012; 379:1498–507. Tresiba® - insulin degludec Literature Review • Included: Type II diabetics, age >18, diagnosed >6 months, HbA1c 7.0-10.0 with current insulin treatment for at least 3 months • Excluded: Use of GLP-1 or rosiglitazone in last 3 months, CV event within previous 6 months, uncontrolled HTN, pregnancy, impaired renal/hepatic function Garber A, et al. Lancet. 2012; 379:1498–507. Tresiba® - insulin degludec Literature Review • Background: Tresiba – Lantus – insulin degludec insulin glargine n=744 n=248 405 (54%) 133 (54%) Race, white 83% 82% Age (years) 59.2 (9.1) 58.1 (10.0) A1c 8.3% (0.8) 8.4% (0.9) Duration of diabetes 13.6 (7.4) 13.4% (6.9) Sex, male Garber A, et al. Lancet. 2012; 379:1498–507. Tresiba® - insulin degludec Literature Review • Intervention: randomize patients (N=1006) at a 3:1 ratio of insulin degludec:insulin glargine once daily • Insulin doses were titrated until patient-reported fasting blood sugars on 3 days previous to appointment averaged 70mg/dL-90mg/dL. • Patients continued for 52 weeks Garber A, et al. Lancet. 2012; 379:1498–507. Tresiba® - insulin degludec Literature Review • Results: Tresiba – insulin degludec Lantus – insulin glargine 1.10% 1.18% Difference of 0.08 (95%CI -0.05 to 0.21) Mean decrease in fasting BG 41.4 mg/dl 36.0 mg/dL Difference of -0.29 (95%CI -0.65 to 0.06) Patients reaching A1c <7% 368 (49%) 124 (50%) Mean A1c decrease Garber A, et al. Lancet. 2012; 379:1498–507. Tresiba® - insulin degludec Literature Review • Safety Outcome: Hypoglycemia Tresiba – insulin degludec Lantus – insulin glargine Severe 34 (5%) 11 (4%) Overall 609 (81%) 206 (82%) Nocturnal 298 (40%) 119 (47%) Garber A, et al. Lancet. 2012; 379:1498–507. Tresiba® - insulin degludec Literature Review Safety outcome: hypoglycemia (individual episodes) Tresiba – insulin degludec Lantus – insulin glargine Rate ratio insulin degludec: insulin glargine (95% CI) Pvalue Severe (rate per PYE) 41 (0.06) 12 (0.05) N/A N/A Overall (rate per PYE) 7437 (11.09) 3120 (13.63) 0.82 (0.69-0.99) 0.0359 Nocturnal (rate per PYE) 930 (1.39) 422 (1.84) 0.75 (0.58-0.99) 0.0359 Garber A, et al. Lancet. 2012; 379:1498–507. Tresiba® - insulin degludec Literature Review BEGIN Basal-bolus Type II • Conclusion: Insulin degludec is non- inferior to insulin glargine in HbA1c lowering • May have benefit of reduced rates of nocturnal hypoglycemia and hypoglycemia overall Garber A, et al. Lancet. 2012; 379:1498–507. Tresiba® - insulin degludec Summary • Tresiba, insulin degludec, is a new long-acting insulin similar in administration and dosing to Levemir and Lantus. Insulin degludec forms hexamers after injection. • Suggested monitoring with home glucose and A1c are similar to other diabetes agents • Hypoglycemia, injection site reactions, and weight gain are similar to other insulins • Does not have any true drug-drug interactions, caution use with agents which may further lower glucose, offset glucose lowering effect, or mask Sx hypoglycemia • Isulin degludec will be available in early 2016 in 3mL “Flextouch” pens Tresiba® - insulin degludec References 1. Tresiba [package insert]. Bagsvaerd, Denmark: Novo Nordisk; 2015. 2. Garber A, King A et al. Insulin degludec, an ultralongacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes. Lancet. 2012; 379:1498–507.