Divergent Hypoglycemic Effects of Hepatic-Directed Prandial Insulin: A 6-Month Phase 2b Study in Type 1 Diabetes
| Autor: | Nathan J. Cohen, Marc S. Penn, David C. Klonoff, Bruce W. Bode, Douglas B. Muchmore, W. Blair Geho |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Blood Glucose Male medicine.medical_specialty endocrine system diseases Endocrinology Diabetes and Metabolism medicine.medical_treatment 030209 endocrinology & metabolism Hypoglycemia Gastroenterology law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial Double-Blind Method law Diabetes mellitus Internal medicine Internal Medicine medicine Insulin lispro Humans Hypoglycemic Agents Insulin Tissue Distribution 030212 general & internal medicine Meals Advanced and Specialized Nursing Glycated Hemoglobin Type 1 diabetes Insulin Lispro Dose-Response Relationship Drug business.industry Blood Glucose Self-Monitoring nutritional and metabolic diseases Middle Aged medicine.disease Postprandial Period Clinical trial Dose–response relationship Diabetes Mellitus Type 1 Treatment Outcome Liver Female business medicine.drug |
| Zdroj: | Diabetes care. 42(11) |
| ISSN: | 1935-5548 |
| Popis: | OBJECTIVE Hepatic-directed vesicle insulin (HDV) uses a hepatocyte-targeting moiety passively attaching free insulin, improving subcutaneous insulin’s hepatic biodistribution. We assessed HDV-insulin lispro (HDV-L) versus insulin lispro (LIS) in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Insulin Liver Effect (ISLE-1) was a 26-week, phase 2b, multicenter, randomized, double-blind, noninferiority trial. RESULTS Among 176 randomized participants (HDV-L n = 118, LIS n = 58), the difference in change from baseline A1C was 0.09% (95% CI −0.18% to 0.35%), confirming noninferiority (prespecified margin ≤0.4%). Overall, there were no statistically significant differences between treatments for hypoglycemia or insulin dosing. However, baseline A1C modified the treatment group effect (interaction P < 0.001) on clinically apparent hypoglycemia designated by treatment-blinded investigators as severe. Thus, at higher baseline A1C, there was less hypoglycemia and lower insulin dosing with similar A1C outcomes during HDV-L versus LIS, whereas greater risk of hypoglycemia despite similar A1C outcomes and insulin doses was observed with lower baseline A1C. Among poorly controlled participants (A1C ≥8.5%), incidence rates of severe hypoglycemia in the HDV-L and LIS arms were 69 and 97 events/100 person-years, respectively (P = 0.03), whereas with A1C CONCLUSIONS Hepatic biodistribution of HDV-L appears to potentiate insulin effect in T1D, with divergent clinical outcomes in hypoglycemia dependent on baseline A1C. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|