Zealand Pharma A/s · OMXCOP:ZEAL
Zealand Pharma A/s — Investor Day (2015)
42 slides from Zealand Pharma A/s's investor day presentation, 2015
Slide 1: Hypoglycemia in Diabetes - a major challenge for better disease management
Hypoglycemia in Diabetes Hypoglycemia in Diabetes - a major challenge for better disease management Kirsten Nørgaard Chief Physician, MD, DrMedSci, MHPE Department of Endocrinology Hvidovre University Hospital Denmark Zealand Pharma
Slide 2: Outline
Hypoglycemia in Diabetes Outline • Occurrence and impact of hypoglycemia • Treatment approaches to avoid and treat hypoglycemia • Insulin pumps and CGM – influence on hypoglycemia? • What can s.c. glucagon potential add to the treatment: • In closed-loop systems • In open-loop systems Zealand Pharma
Slide 3: Outline
Hypoglycemia in Diabetes Outline • Occurrence and impact of hypoglycemia • Treatment approaches to avoid and treat hypoglycemia • Insulin pumps and CGM – influence on hypoglycemia? • What can s.c. glucagon potential add to the treatment: • In closed-loop systems • In open-loop systems Zealand Pharma
Slide 4: Definitions
Hypoglycemia in Diabetes Definitions • Mild hypoglycemia: • a person can self-treat • Detected by the person because of symptoms or a random low BG measurement • BG limit vary (<3.0, <3.5, <3.9 mmol/l) or • May be detected by others because of person’s appearance • Severe hypoglycemia: • need for th
Slide 5: Mild hypoglycemia
Hypoglycemia in Diabetes Mild hypoglycemia • Definition not universal • Patients do not recall very well • Limited data on occurrence • Overall average: 1-2 episodes per patient per week • Low HbA1c → More episodes of mild hypoglycemia Zealand Pharma
Slide 6: Consequences of hypoglycemia
Hypoglycemia in Diabetes Consequences of hypoglycemia • Short-term: • Unpleasant for patients • Associated with psychological distress • Affects driving ability, working ability etc. • Acute morbidity: injuries, cardiovascular and cerebrovascular events • Increased mortality (up to 4-10 % of T1D die
Slide 7: Dilemma
Hypoglycemia in Diabetes Dilemma 1) Any rise in A1c causes more damage - any fall helps Better 2) Severe hypoglycemia is the downside Zealand Pharma
Slide 8: Hypoglycemia in Diabetes
Hypoglycemia in Diabetes Zealand Chillaron et al , Metabolism, 2014 Pharma
Slide 9: DCCT randomized study
DCCT: randomized study in 1500 type 1 Hypoglycemia in Diabetes patients treated conventionally (insulin twice daily) or intensively (MDI/insulin pumps) Zealand Pharma
Slide 10: Severe hypoglycemia: results from the T1D Exchange Clinic Registry
Hypoglycemia in Diabetes Severe hypoglycemia: results from the T1D Exchange Clinic Registry * Zealand Weinstock et al. J Clin Endocrin Metab 2013 Pharma
Slide 11: Severe hypoglycemia by diabetes treatment and duration
Severe hypoglycemia in Type 1 and Type 2 Hypoglycemia in Diabetes patients depending on diabetes treatment and duration Zealand Frier, Nat Rev Endocrinol 2014 Pharma
Slide 12: Severe hypoglycemia is frequent but few patients account for most attacks
Hypoglycemia in Diabetes Severe hypoglycemia is frequent – but few patients account for most attacks Zealand Pedersen-Bjerggard et al. Diabetes Metabol Res Rev, 2004 Pharma
Slide 13: Outline
Hypoglycemia in Diabetes Outline • Occurrence and impact of hypoglycemia • Treatment approaches to avoid and treat hypoglycemia • Insulin pumps and CGM – influence on hypoglycemia? • What can s.c. glucagon potential add to the treatment: • In closed-loop systems • In open-loop systems Zealand Pharma
Slide 14: How to avoid severe hypoglycemia
Hypoglycemia in Diabetes How to avoid severe hypoglycemia • Re-education • 2-3 weeks completely avoidance of hypoglycemia • Decreasing HbA1c goals • Increase blood glucose measurements • Changing insulin regimen to insulin pumps +/- continuous glucose measurements Zealand Pharma
Slide 15: Treating episodes of severe hypoglycemia
Hypoglycemia in Diabetes Treating episodes of severe hypoglycemia 1. Sc. or im. glucagon injection by caregivers at home • Studies have shown: • Requires 9 steps before use • Glucagon is underused • Prescription of glucagon → reduce emergency visits for severe hypoglycemia 2. Iv. glucose injection b
Slide 16: How to avoid mild hypoglycemia?
Hypoglycemia in Diabetes How to avoid mild hypoglycemia? • Fear of hypoglycemia leads to: • Patients under-bolus with insulin • Eat more than needed- especially at night • Avoidance of physical activity • Increase self-measurements of blood glucose • Change insulin and diet regimen Zealand Pharma
Slide 17: Treating episodes of mild hypoglycemia
Hypoglycemia in Diabetes Treating episodes of mild hypoglycemia • Extra carbohydrates • Reducing insulin • (Or in the future: maybe a microdose of glucagon) Zealand Pharma
Slide 18: Outline
Hypoglycemia in Diabetes Outline • Occurrence and impact of hypoglycemia • Treatment approaches to avoid and treat hypoglycemia • Insulin pumps and CGM – influence on hypoglycemia? • What can s.c. glucagon potential add to the treatment: • In closed-loop systems • In open-loop systems Zealand Pharma
Slide 19: Insulin pump treatment
Hypoglycemia in Diabetes Insulin pump treatment Zealand Pharma
Slide 20: Insulin pump infusion set connection
Hypoglycemia in Diabetes Connection with infusion set to the abdominal subcutaneous tissue Zealand Pharma
Slide 21: Principle for insulin pump treatment
Principle for insulin pump treatment: Analogue insulin as a continuous infusion + bolus insulin Breakfast Lunch Dinner Plasma insulin Bolus Bolus Bolus Basal infusion 4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00
Slide 22: Intra-individual variability in insulin action
Hypoglycemia in Diabetes Intra-individual variability in insulin action • Short acting analogues: 15 % • Short acting human insulin: 24 % • NPH: 68 % • Long acting analogues: • Glargine: appr. 38 % • Detemir: appr. 38 % • Tresiba: 25 % • Short acting analogues in insulin pumps: 5% Zealand Pharma
Slide 23: Meta-analysis of MDI versus insulin pump
Severe hypoglycaemia and glycaemic control in Type 1 diabetes: Hypoglycemia in Diabetes meta‐analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion Pickup. Diabetic Medicine, 2008 Insulin pumps reduce SH by 80 % Zealand Pharma
Slide 24: Interstitial glucose vs BG
Hypoglycemia in Diabetes Interstitiel glucose vs BG G Glu lucose cose SSen ensor sor In terstitial flu id glu cose (G 2) is alm ost alw ay s com p arab le w ith blood glu cose (G 1) 9 Zealand Pharma
Slide 25: Glucose-oxidase sensors
Hypoglycemia in Diabetes Glukose-oxidase sensors D escr iption - Sensor G luconic A cid G lucose O xidase 0.6 volts G lucose + O 2 H 2O 2 2H + + O 2 + 2e- Sensor contains the enzym e glucose oxidase, w hich conver ts glucose into an electr onic signal 7 Zealand Pharma
Slide 26: CGM with an insulin pump or stand alone
Hypoglycemia in Diabetes CGM with an insulin pump or as stand alone Animas+Dexcom Medtronic VEO Minimed 640G Zealand Medtronic Guardian Abbott Navigator Dexcom Pharma
Slide 27: Annual rates of SH before and after starting CGM
Annual rates of SH, requiring third-party help at baseline Hypoglycemia in Diabetes and 12 months after starting CGM Zealand Choudhary et al. Dia Care 2013 Pharma
Slide 28: Insulin pump with sensor and Low Glucose Suspend
Hypoglycemia in Diabetes 95 patients known with severe hypoglycemia randomized to insulin pump or insulin pump with sensor and Low Glucose Suspend Zealand Ly et al. JAMA 2013 Pharma
Slide 29: Outline
Hypoglycemia in Diabetes Outline • Occurrence and impact of hypoglycemia • Treatment approaches to avoid and treat hypoglycemia • Insulin pumps and CGM – influence on hypoglycemia? • What can s.c. glucagon potential add to the treatment: • In closed-loop systems • In open-loop systems Zealand Pharma
Slide 30: Closed Loop
Hypoglycemia in Diabetes Closed Loop Zealand Pharma
Slide 31: A closed loop system with one hormone: insulin
A closed loop system with one hormone…… Insulin
Slide 32: Closed loop in adolescents
Hypoglycemia in Diabetes 16 type 1 Age: 12-18 years Closed loop: Time in hypo Mean BG night Mean BG 24 h Zealand Den kunstige bugspytkirtel Pharma
Slide 33: A closed loop with dual hormone: glucagon and insulin
A closed loop with dual hormone! Glucagon Insulin
Slide 34: Randomised study: open loop vs dual-hormone closed loop
Randomised study in 52 Type (adults and adolescents) in 5 days CSII- open loop or dual-hormone closed loop Open-loop Closed-loop Mean BG 7,8 mmol/l 7,4 mmol/l * % time lower than 3.9 7,3 % 4,1 % * mmol/l Intervention with 0.6 /day 0.3/day glucose due to hypo
Slide 35: Children in camps: pump, single and dual hormone closed loop
33 children 8-18 years 3 nights in camps: - Control night with insulin pump only - Closed loop: single hormone - insulin - Closed loop: dual hormone – insulin and glucagon
Slide 36: Time 23.00
Time 23.00 7.00 23.00 7.00 23.00 7.00
Slide 37: DiaCon - Danish approach using insulin and glucagon
DiaCon – Danish approach – use two hormones: insulin and glucagon
Slide 38: Open-Loop
Zealand Pharma Hypoglycemia in Diabetes Open-Loop +
Slide 39: Glucose response to different sc. doses of glucagon
Glucose response to different sc. doses of Hypoglycemia in Diabetes glucagon to type 1 patients after hypoglycemia due to a small over dose of insulin Zealand Ranjan and Nørgaard, Submitted to Diabetes Obesity and Metabolism, 2015 Pharma
Slide 40: Plasma glucagon and serum insulin aspart
Hypoglycemia in Diabetes P la s m a g lu c a g o n S e r u m in s u lin a s p a r t 400 24 M ean + SEM S a lin e 350 1 0 0 g g lu c a g o n 22 2 0 0 g g lu c a g o n 3 0 0 g g lu c a g o n 20 300 18 p > 0 .5 250 m U / L p m o l/l 16 200 p < 0 .0 0 1 14 150 12 100 10 50 8 0 0 -1 2 0 -6 0 0 60
Slide 41: Advanced Open-Loop?
Hypoglycemia in Diabetes Advanced Open-Loop? or Zealand Pharma
Slide 42: Conclusions
Hypoglycemia in Diabetes Conclusions • Fear and risk of hypoglycemia are still major problems in diabetes treatment • Glucagon in soluble form is needed to treat more episodes of severe hypoglycemic attacks at home • Soluble glucagon as a treatment tool for mild hypoglycemia in open loop systems sho