Achieving Optimal Glycaemic Control: Can Insulin Deliver?

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Presentation transcript:

Achieving Optimal Glycaemic Control: Can Insulin Deliver? David Russell-Jones Thomas Danne Andreas Liebl

Recommended Targets for PPG PPG target (1–2 hours post meal) ADA/EASD1,2 < 10 mmol/L < 180 mg/dL AACE3 < 7.8 mmol/L < 140 mg/dL IDF4 < 9 mmol/L < 160 mg/dL 3:03 1. Inzucchi SE, et al. Diabetologia. 2015;58:429-42. 2. ADA Guidelines. Diabetes Care. 2017;40 Suppl 1:S48-56. 3. Garber AJ, et al. Endocr Pract. 2016;22;84-113. 4. International Diabetes Federation. Guideline for Management of PostMeal Glucose in Diabetes. Available at: www.idf.org/sites/default/files/postmeal%20glucose%20guidelines.pdf. Accessed February 2017. AACE, American Association of Clinical Endocrinologists; ADA, American Diabetes Association; EASD, European Association for the Study of Diabetes; IDF, International Diabetes Federation; PPG, postprandial glucose.

PPG Contributes to HbA1c1,2 FPG HbA1c PPG is the main contributor to HbA1c in patients near target HbA1c2 Relative to the influence of FPG, PPG is more closely associated with HbA1c control3 If FPG is at target (< 100 mg/dL), 64% of patients achieve HbA1c < 7.0%4 If PPG is at target (< 140 mg/dL), 94% of patients achieve HbA1c < 7.0%4 5:47 1. Monnier L, et al. Diabetes Care. 2007;30:263-9. 2. Monnier L, et al. Endocr Pract. 2006;12 Suppl 1:42-6. 3. Ketema L, et al. Arch Public Health. 2015;73:43. 4. Woerle HJ, et al. Diabetes Res Clin Pract. 2007;77:280-5. FPG, fasting plasma glucose; HbA1c, glycated haemoglobin A1c.

Patient Profile 1 18-year-old male Diagnosed with type 1 diabetes 5 years ago Using continuous glucose monitoring Meal Preprandial Time (hours) 400 300 200 140 70 40 +5:00 +1:00 −1:00 Sensor glucose (mg/dL) 6:48

24-hour glucose profiles over 7 days Patient Profile 2 58-year-old male Diagnosed with type 2 diabetes 8 years ago Abdominal obesity (BMI 30 kg/m2) MI 2 years ago Normal eating habits Diabetes treatment Metformin (1,000 mg b.i.d.) Empagliflozin (10 mg once daily) Insulin glargine (48 units at bedtime) Insulin lispro (50 units before breakfast, 24 units before lunch and dinner) 24-hour glucose profiles over 7 days We Aug 31 Th Sep 01 Fr Sep 02 Sa Sep 03 Su Sep 04 Mo Sep 05 Tu Sep 06 50 100 150 200 250 300 350 400 mg/dL 8:43 00:00 03:00 12:00 15:00 18:00 21:00 06:00 09:00 b.i.d., twice daily; BMI, body-mass index; MI, myocardial infarction.

Ultra-Fast-Acting IAsp: A New Formulation of IAsp Niacinamide: absorption modifier Vitamin B3 L-arginine: added for stability 13:18 IAsp Naturally occurring amino acid IASp, insulin aspart. Heise T, et al. Diabetes Obes Metab. 2015;17:682-8.

Free IAsp concentration (pmol/L) Nominal time (minutes) Ultra-Fast-Acting IAsp: Early Onset of Appearance and 2-Fold Higher Concentration After 30 Minutes1 Treatment: Ultra-fast-acting IAsp IAsp 400 AUC0–30 minutes (pmol*h/L) AUC0–1 hours (pmol*h/L) AUC0–2 hours (pmol*h/L) Ultra-fast-acting IAsp/IAsp 1 2 3 4 5 Ratio [95% CI] 2.05 [1.76; 2.38] 1.28 [1.15; 1.43] 1.04 [0.95; 1.14] 300 Free IAsp concentration (pmol/L) 200 Onset of appearance: 4.9 minutes (ultra-fast-acting IAsp) vs 11.2 minutes (IAsp) Ratio 0.43 [95% CI 0.36; 0.51] 100 AUC0–12 hours (pmol*h/L) 0.96 [0.87; 1.06] 14:59 30 60 90 120 Nominal time (minutes) Consistent pharmacokinetic profile in children,2 adolescents,2 adults,2 and elderly3 1. Heise T, et al. Diabetes Obes Metab. 2015;17:682-8. 2. Danne T, et al. Diabetes. 2015;64 Suppl 1:A247 (abstract 976-P). 3. Heise T, et al. Drugs Aging. 2017;34:29-38. AUC, area under the curve; CI, confidence interval.

Early Glucose-Lowering Effects AUC0–30 minutes (mg/kg) AUC0–1 hour (mg/kg) AUC0–2 hours (mg/kg) Ultra-fast-acting IAsp/IAsp 1 2 3 4 5 Ratio [95% CI] 1.48 [1.13; 2.02] 1.31 [1.18; 1.46] 1.10 [1.00; 1.22] AUC0–12 hours (mg/kg) 0.98 [0.87; 1.11] 15:48 Ultra-fast-acting IAsp provided a 1.5-fold greater early glucose-lowering effect compared with IAsp, while maintaining a similar total glucose-lowering effect Heise T, et al. Diabetes Obes Metab. 2015;17:682-8.

PPH was a significant predictor of cardiovascular events and mortality Impact of PPH For patients, PPH can affect mood and cognitive function1 PPH is also associated with: Microvascular complications2,3 Cardiovascular events4 Cardiovascular5 and all-cause mortality4,5 San Luigi Gonzaga diabetes study: 14-year follow-up of 505 patients with type 2 diabetes4 Outcome HR [95% CI]; p value Cardiovascular events 1.452 [1.057; 1.994]; 0.021 All-cause mortality 1.846 [1.306; 2.610]; 0.001 18:15 PPH was a significant predictor of cardiovascular events and mortality 1. Sommerfield AJ, et al. Diabetes Care. 2004;27:2335-40. 2. Shichiri M, et al. Diabetes Care. 2000;23 Suppl 2:B21-9. 3. UKPDS Group. Lancet. 1998;352:837-53. 4. Cavalot F, et al. Diabetes Care. 2011;34:2337-43. 5. DECODE Study Group. Arch Intern Med. 2001;161:397-404. PPH, postprandial hyperglycaemia.

Impact of Ultra-Fast-Acting Insulin Analogues and Future Challenges Ultra-fast-acting insulin analogues support intensive insulin therapy strategies for patients with diabetes1,2 Convenience and flexibility of ultra-fast-acting insulin analogues may help reduce glycaemic variability1–3 Future challenges include integrating ultra-fast-acting insulin analogues into strategies utilizing new technologies, such as closed-loop systems4 20:46 1. Bowering K, et al. Diabetes. 2016;65 Suppl 1:A63 (abstract 240-OR). 2. Russell-Jones D, et al. Diabetes. 2016;65 Suppl 1:A77 (abstract 293-OR). 3. Heise T, et al. Diabetes Obes Metab. 2015;17:682-8. 4. Kowalski A. Diabetes Care. 2015;38:1036-43.