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Double-Blind Mealtime Faster-Acting Insulin Aspart vs. Insulin Aspart in Basal-Bolus Improves Glycemic Control in T1D: The Onset® 1 Trial
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Abstracts / Can J Diabetes 40 (2016) S27–S74
Table 1 Pharmacokinetic and pharmacodynamic results for faster aspart vs. IAsp PK endpoints (insulin exposurea)
n=261/256b
PD endpoints (glucose-lowering effect)
n=163/160b
Onset
Treatment difference Faster aspart–IAsp [95% CI] (min)
Onset
Treatment difference Faster aspart–IAsp [95% CI] (min)
Onset of appearance t50%Cmax
–4.9 [–5.3;–4.4] –9.5 [–10.7;–8.3]
Onset of action t50%GIRmax
–4.9 [–6.9;–3.0] –9.5 [–12.5;–6.4]
Early exposure
Treatment ratio Faster aspart/IAsp [95% CI]
Early effect
Treatment ratio Faster aspart/IAsp [95% CI]
AUC0–15 min AUC0–30 min AUC0–1h AUC0–2h
3.83 [3.41;4.29] 2.01 [1.87;2.17] 1.32 [1.26;1.39] 1.10 [1.06;1.14]
– AUCGIR,0–30 min AUCGIR,0–1h AUCGIR,0–2h
– 1.74 [1.47;2.10]c 1.34 [1.25;1.43] 1.13 [1.07;1.19]
Total exposure
Treatment ratio Faster aspart/IAsp [95% CI]
Total effect
Treatment ratio Faster aspart/IAsp [95% CI]
AUC0–12h Cmax
1.01 [0.98;1.04] 1.04 [1.00;1.08]
AUCGIR,0–12h GIRmax
0.98 [0.94;1.03] 1.01 [0.96;1.05]
159 Withdrawn
a
Based on free serum IAsp. n is number of profiles contributing to the analysis for faster aspart/IAsp. c treatment ratio and 95% CI estimated using Fieller’s method. AUC, area under the curve; CI, confidence interval; Cmax, maximum observed concentration; GIRmax, maximum glucose infusion rate; onset of appearance, time from dosing until the first time serum IAsp concentration≥lower limit of quantification. b
158 Double-Blind Mealtime Faster-Acting Insulin Aspart vs. Insulin Aspart in Basal-Bolus Improves Glycemic Control in T1D: The Onset® 1 Trial DAVID RUSSELL-JONES†, BRUCE W. BODE†, CHRISTOPHE DE BLOCK†, EDWARD FRANEK†, SIMON HELLER†, CHANTAL MATHIEU†, ATHENA PHILIS-TSIMIKAS†, LUDGER ROSE†, VINCENT WOO†, ANNE BIRK ØSTERSKOV†, TINA GRAUNGAARD†, ARASH PAKSERESHT*,†, RICHARD BERGENSTAL† Mississauga, ON Limiting excursions of postprandial glucose (PPG) is desirable in people with diabetes. This multicentre, treat-to-target, phase 3 trial evaluated the efficacy of faster-acting insulin aspart (faster aspart) in type 1 diabetes (T1D). Primary endpoint was change from baseline in HbA1c after 26 weeks treatment. Post run-in, adult subjects were randomized to double-blind mealtime faster aspart (n=381), insulin aspart (IAsp) (n=380) or open-label postmeal faster aspart (n=382); each with insulin detemir. HbA1c was reduced for faster aspart and IAsp (Figure), confirming noninferiority to IAsp for both mealtime and postmeal dosing (estimated treatment difference [ETD] [95% confidence interval]: mealtime, −0.15% [−0.23; −0.07]); postmeal, 0.04% [−0.04; 0.12]); HbA1c reduction was significantly greater for mealtime faster aspart vs. IAsp. Superiority to IAsp for 2-h PPG increment during a standardized meal test was confirmed for faster aspart (ETD: −0.67 mmol/L [−1.29; −0.04]; −12.01 mg/dL [−23.33; −0.70]). One-hour PPG increment was also reduced (ETD: −1.18 mmol/L [−1.65; −0.71]; −21.21 mg/dL [−29.65; −12.77]). No significant differences in overall rate of severe or confirmed hypoglycemic episodes (plasma glucose <3.1 mmol/L [56 mg/dL]). In summary, faster aspart effectively improved glycemic control with superior PPG control for mealtime faster aspart vs. IAsp, representing a clinical advance in treating T1D.
160 A National Survey of Physicians’ and Allied Health Professionals’ Practices and Perspectives Regarding Hypoglycemia Management: The InHYPO-DM Study SONJA REICHERT*,†, STEWART HARRIS†, SELAM MEQUANINT, BRIDGET L. RYAN, SUSAN WEBSTER-BOGAERT, ALEXANDRIA RATZKI-LEEWING, JUDITH B. BROWN London, ON Background: Hypoglycemia is a known limitation for effective glycemic management. Aim: To explore diabetes care providers’ practices and perspectives regarding hypoglycemia management. Methods: Guided by the Theoretical Domains Framework, an online survey was developed to explore factors that impact healthcare providers’ (HCP) potential to effectively help patients manage hypoglycemia. The survey was distributed to physicians and pharmacists who provide care to patients with diabetes (via professional targeted marketing) and nurses and dietitians (via Canadian Diabetes Association). Results: A total of 671 physicians and allied health professionals (AHPs) (nurses [37%], physicians [29%], dietitians [6%], pharmacists [10%] and other [7%]) completed the survey. The majority 428 (90%) of AHPs were certified diabetes educators (CDEs) (Table 1). Overall, 65% of respondents considered helping patients manage hypoglycemia to be a challenge. Forty-seven per cent of physicians, 35% of non-CDE AHPs and 33% CDE AHPs ranked their knowledge of hypoglycemia management as moderate/low. Only 21% of physicians and 40% of non-CDE AHPs believed that their practice was always informed by current evidence and guidelines. Fiftysix per cent of physicians and 43% of AHPs indicated that they worry about hypoglycemia and that this caused them to modify recommended guidelines when individualizing their patients’ management of hypoglycemia. Conclusion: This study, the largest survey of its kind in Canada, highlighted the lack of HCPs’ knowledge and capacity in helping patients manage hypoglycemia. The survey identified gaps between recommended guidelines and care provided to patients. Thus, a strategy that can improve knowledge of hypoglycemia management is needed for HCPs in Canada.
Abstracts / Can J Diabetes 40 (2016) S27–S74
Table 1 Pharmacokinetic and pharmacodynamic results for faster aspart vs. IAsp PK endpoints (insulin exposurea)
n=261/256b
PD endpoints (glucose-lowering effect)
n=163/160b
Onset
Treatment difference Faster aspart–IAsp [95% CI] (min)
Onset
Treatment difference Faster aspart–IAsp [95% CI] (min)
Onset of appearance t50%Cmax
–4.9 [–5.3;–4.4] –9.5 [–10.7;–8.3]
Onset of action t50%GIRmax
–4.9 [–6.9;–3.0] –9.5 [–12.5;–6.4]
Early exposure
Treatment ratio Faster aspart/IAsp [95% CI]
Early effect
Treatment ratio Faster aspart/IAsp [95% CI]
AUC0–15 min AUC0–30 min AUC0–1h AUC0–2h
3.83 [3.41;4.29] 2.01 [1.87;2.17] 1.32 [1.26;1.39] 1.10 [1.06;1.14]
– AUCGIR,0–30 min AUCGIR,0–1h AUCGIR,0–2h
– 1.74 [1.47;2.10]c 1.34 [1.25;1.43] 1.13 [1.07;1.19]
Total exposure
Treatment ratio Faster aspart/IAsp [95% CI]
Total effect
Treatment ratio Faster aspart/IAsp [95% CI]
AUC0–12h Cmax
1.01 [0.98;1.04] 1.04 [1.00;1.08]
AUCGIR,0–12h GIRmax
0.98 [0.94;1.03] 1.01 [0.96;1.05]
159 Withdrawn
a
Based on free serum IAsp. n is number of profiles contributing to the analysis for faster aspart/IAsp. c treatment ratio and 95% CI estimated using Fieller’s method. AUC, area under the curve; CI, confidence interval; Cmax, maximum observed concentration; GIRmax, maximum glucose infusion rate; onset of appearance, time from dosing until the first time serum IAsp concentration≥lower limit of quantification. b
158 Double-Blind Mealtime Faster-Acting Insulin Aspart vs. Insulin Aspart in Basal-Bolus Improves Glycemic Control in T1D: The Onset® 1 Trial DAVID RUSSELL-JONES†, BRUCE W. BODE†, CHRISTOPHE DE BLOCK†, EDWARD FRANEK†, SIMON HELLER†, CHANTAL MATHIEU†, ATHENA PHILIS-TSIMIKAS†, LUDGER ROSE†, VINCENT WOO†, ANNE BIRK ØSTERSKOV†, TINA GRAUNGAARD†, ARASH PAKSERESHT*,†, RICHARD BERGENSTAL† Mississauga, ON Limiting excursions of postprandial glucose (PPG) is desirable in people with diabetes. This multicentre, treat-to-target, phase 3 trial evaluated the efficacy of faster-acting insulin aspart (faster aspart) in type 1 diabetes (T1D). Primary endpoint was change from baseline in HbA1c after 26 weeks treatment. Post run-in, adult subjects were randomized to double-blind mealtime faster aspart (n=381), insulin aspart (IAsp) (n=380) or open-label postmeal faster aspart (n=382); each with insulin detemir. HbA1c was reduced for faster aspart and IAsp (Figure), confirming noninferiority to IAsp for both mealtime and postmeal dosing (estimated treatment difference [ETD] [95% confidence interval]: mealtime, −0.15% [−0.23; −0.07]); postmeal, 0.04% [−0.04; 0.12]); HbA1c reduction was significantly greater for mealtime faster aspart vs. IAsp. Superiority to IAsp for 2-h PPG increment during a standardized meal test was confirmed for faster aspart (ETD: −0.67 mmol/L [−1.29; −0.04]; −12.01 mg/dL [−23.33; −0.70]). One-hour PPG increment was also reduced (ETD: −1.18 mmol/L [−1.65; −0.71]; −21.21 mg/dL [−29.65; −12.77]). No significant differences in overall rate of severe or confirmed hypoglycemic episodes (plasma glucose <3.1 mmol/L [56 mg/dL]). In summary, faster aspart effectively improved glycemic control with superior PPG control for mealtime faster aspart vs. IAsp, representing a clinical advance in treating T1D.
160 A National Survey of Physicians’ and Allied Health Professionals’ Practices and Perspectives Regarding Hypoglycemia Management: The InHYPO-DM Study SONJA REICHERT*,†, STEWART HARRIS†, SELAM MEQUANINT, BRIDGET L. RYAN, SUSAN WEBSTER-BOGAERT, ALEXANDRIA RATZKI-LEEWING, JUDITH B. BROWN London, ON Background: Hypoglycemia is a known limitation for effective glycemic management. Aim: To explore diabetes care providers’ practices and perspectives regarding hypoglycemia management. Methods: Guided by the Theoretical Domains Framework, an online survey was developed to explore factors that impact healthcare providers’ (HCP) potential to effectively help patients manage hypoglycemia. The survey was distributed to physicians and pharmacists who provide care to patients with diabetes (via professional targeted marketing) and nurses and dietitians (via Canadian Diabetes Association). Results: A total of 671 physicians and allied health professionals (AHPs) (nurses [37%], physicians [29%], dietitians [6%], pharmacists [10%] and other [7%]) completed the survey. The majority 428 (90%) of AHPs were certified diabetes educators (CDEs) (Table 1). Overall, 65% of respondents considered helping patients manage hypoglycemia to be a challenge. Forty-seven per cent of physicians, 35% of non-CDE AHPs and 33% CDE AHPs ranked their knowledge of hypoglycemia management as moderate/low. Only 21% of physicians and 40% of non-CDE AHPs believed that their practice was always informed by current evidence and guidelines. Fiftysix per cent of physicians and 43% of AHPs indicated that they worry about hypoglycemia and that this caused them to modify recommended guidelines when individualizing their patients’ management of hypoglycemia. Conclusion: This study, the largest survey of its kind in Canada, highlighted the lack of HCPs’ knowledge and capacity in helping patients manage hypoglycemia. The survey identified gaps between recommended guidelines and care provided to patients. Thus, a strategy that can improve knowledge of hypoglycemia management is needed for HCPs in Canada.