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mL in a Patient-Level Meta-Analysis of EDITION 1, 2 and 3
Abstracts / Can J Diabetes 40 (2016) S27–S74
to organize their care (e.g. booking appointments), teaching them the differences between pediatric- and adult-oriented care and developing their self-management skills (e.g. insulin adjustments). Most reported conducting self-care assessments to establish a care plan, but only 4% used a written tool. Only 32% had a system to identify patients lost to follow up. Transition barriers included difficulty accessing psychosocial services, insufficient clinic time, patients’ lack of motivation and patients’ inadequate preparation for transition. Most physicians (87%) were interested in having additional tools, including a self-care management tool and a registry to track those lost to follow up. Conclusions: Our findings highlight the need to better engage adult care providers in transition care practices and to improve pediatricadult provider collaboration in order to support the emerging adult through the transition process. 128 Safety and Efficacy of a Pragmatic Self-Titration 1 Unit/Day (INSIGHT) Algorithm for Insulin Glargine 300 U/mL (Gla-300) LORI BERARD*, STEWART B. HARRIS, JEAN-FRANCOIS YALE, MÉLANIE GROLEAU, PASHA JAVADI, JOHN STEWART Winnipeg, MB GLA-300 provides a flat and prolonged PK/PD profile with a comparable glycemic control and less hypoglycemia vs. glargine 100 U/mL (GLA-100). In the EDITION trials, insulin was titrated weekly or no more than every 3 days by the HCP based on the median last 3 fasting pre-breakfast SMPGs. With GLA-100, the INSIGHT 1 U/day self-titration protocol is widely used in Canada. The objective of this 12-week, randomized, descriptive pilot study (NCT02401243) was to compare safety and efficacy of 2 titration algorithms, INSIGHT and EDITION, for GLA-300 in T2DM patients (insulin naïve or on basal insulin±OAD). The mean baseline characteristics in 212 randomized patients were age 62.3 years, BMI 34.2 kg/m2, A1c 8.4%, insulin naïve 37.0%, prior basal insulin dose 57.2 U. Comparable number of patients in each titration group reached primary endpoint of a fasting SMPG ≤5.6 mmol/L without nocturnal (0:00 to 6:00 h) hypoglycemia (SMPG ≤3.9 mmol/L or symptomatic or severe) at 12 weeks (INSIGHT-algorithm 22.8%; EDITION 20.6%). No between-treatment differences in severe hypoglycemia were noted (1 INSIGHT-algorithm vs. 3 EDITION). The percentages of patients achieving A1c ≤7% was 28.7% (INSIGHT-algorithm) vs. 28.4% (EDITION) with similar mean A1c (SD) of 7.6% (0.9) at week 12. Similar number of patients experienced nocturnal hypoglycemia (INSIGHT-algorithm 28.7%; EDITION 27.5%). In conclusion, application of a self-titration of 1 U/day algorithm with GLA-300 resulted in a good safety profile, and was effective and comparable to the previously tested EDITION-algorithm. Funding: Study funded by Sanofi. 129 Hypoglycemia as a Function of HbA1c in Type 2 Diabetes (T2DM): Insulin Glargine 300 U/mL in a Patient-Level MetaAnalysis of EDITION 1, 2 and 3 JEAN-FRANÇOIS YALE*, RICCARDO C. BONADONNA, CLAIRE BRULLE-WOHLHUETER, EMMANUELLE BOËLLE-LE CORFEC, PRATIK CHOUDHARY, TIMOTHY S. BAILEY Montreal, QC Basal insulin therapy can be a compromise between achieving glycemic targets and avoiding hypoglycemia, dependent on how intensively insulin is titrated. In the phase 3a EDITION 1, 2 and 3 studies, insulin glargine 300 U/mL (Gla-300) provided equivalent glycemic control to insulin glargine 100 U/mL (Gla-100) with less
S47
hypoglycemia in people with T2DM. The objective of the current analysis was to evaluate rates of confirmed (≤3.9 mmol/L) or severe hypoglycemia over 6 months of treatment with Gla-300 or Gla100 in these EDITION studies, as a function of HbA1c. Meta-analysis was performed on patient-level data, and annualized hypoglycemia rate as a function of HbA1c at Month 6 was fitted using a negative binomial regression model. Adding a treatment-by-HbA1c interaction term to the model did not significantly improve the goodness of fit (interaction p-value 0.937 and 0.829 for anytime [24 h] and nocturnal [00:00 to 05:59 h] hypoglycemia, respectively). Therefore the model without interaction describes the data accurately: people treated with Gla-300 experienced a consistently lower rate of confirmed (≤3.9 mmol/L) or severe hypoglycemia vs. those treated with Gla-100, regardless of HbA1c at Month 6 (Figure). In conclusion, these results suggest that treatment with Gla 300 vs. Gla100 could allow people with T2DM to achieve equivalent glycemic control with less hypoglycemia. Funding: Study supported by Sanofi (NCT01499082, NCT01499095, NCT01676220).
130 Glycemic Control and Hypoglycemia Benefits with Insulin Glargine 300 U/mL (Gla-300) Extend to People with Type 2 Diabetes and Mild-to-Moderate Renal Impairment PETER A. SENIOR*, JAVIER ESCALADA, SERGE HALIMI, MIREILLE BONNEMAIRE, ANNA M.G. CALI, SOAZIG CHEVALIER, JANAKA KARALLIEDDE, ROBERT A. RITZEL Edmonton, AB EDITION 1, 2 and 3 showed that over 6 months, Gla-300 provided comparable glycemic control to glargine 100 U/mL (Gla-100) and less hypoglycemia in people with T2DM. Renal impairment increases the risk of hypoglycemia in people with type 2 diabetes (T2DM). The effects of Gla-300 vs. Gla-100 on HbA1c reduction and hypoglycemia were assessed in renal function subgroups (baseline eGFR ≥30 to <60, ≥60 to <90 and ≥90 mL/min/1.73 m2) in a post hoc patient-level metaanalysis of data from EDITION 1, 2 and 3. Most participants (56%) had baseline eGFR ≥60 to <90 mL/min/1.73 m2 (Table). Non-inferiority for HbA1c reduction (defined in the EDITION studies) was shown for Gla-300 and Gla-100 regardless of renal function; no evidence of heterogeneity of treatment effect was demonstrated across subgroups (p=0.46; Table 1). Risk of confirmed (≤3.9 mmol/L) or severe hypoglycemia was significantly lower for nocturnal events and comparable or lower for anytime (24 h) events for Gla-300 vs. Gla-100 across subgroups. Renal function did not affect the lower rate of nocturnal or any time hypoglycemia (no evidence of heterogeneity of treatment effect across subgroups: p=0.73, p=0.27). Gla-300 provided comparable glycemic control and consistently reduced nocturnal hypoglycemia vs. Gla-100 in participants with T2DM regardless of renal function, with no increase in any time hypoglycemia. Funding: Study funded by Sanofi (NCT01499082, NCT01499095, NCT01676220).
to organize their care (e.g. booking appointments), teaching them the differences between pediatric- and adult-oriented care and developing their self-management skills (e.g. insulin adjustments). Most reported conducting self-care assessments to establish a care plan, but only 4% used a written tool. Only 32% had a system to identify patients lost to follow up. Transition barriers included difficulty accessing psychosocial services, insufficient clinic time, patients’ lack of motivation and patients’ inadequate preparation for transition. Most physicians (87%) were interested in having additional tools, including a self-care management tool and a registry to track those lost to follow up. Conclusions: Our findings highlight the need to better engage adult care providers in transition care practices and to improve pediatricadult provider collaboration in order to support the emerging adult through the transition process. 128 Safety and Efficacy of a Pragmatic Self-Titration 1 Unit/Day (INSIGHT) Algorithm for Insulin Glargine 300 U/mL (Gla-300) LORI BERARD*, STEWART B. HARRIS, JEAN-FRANCOIS YALE, MÉLANIE GROLEAU, PASHA JAVADI, JOHN STEWART Winnipeg, MB GLA-300 provides a flat and prolonged PK/PD profile with a comparable glycemic control and less hypoglycemia vs. glargine 100 U/mL (GLA-100). In the EDITION trials, insulin was titrated weekly or no more than every 3 days by the HCP based on the median last 3 fasting pre-breakfast SMPGs. With GLA-100, the INSIGHT 1 U/day self-titration protocol is widely used in Canada. The objective of this 12-week, randomized, descriptive pilot study (NCT02401243) was to compare safety and efficacy of 2 titration algorithms, INSIGHT and EDITION, for GLA-300 in T2DM patients (insulin naïve or on basal insulin±OAD). The mean baseline characteristics in 212 randomized patients were age 62.3 years, BMI 34.2 kg/m2, A1c 8.4%, insulin naïve 37.0%, prior basal insulin dose 57.2 U. Comparable number of patients in each titration group reached primary endpoint of a fasting SMPG ≤5.6 mmol/L without nocturnal (0:00 to 6:00 h) hypoglycemia (SMPG ≤3.9 mmol/L or symptomatic or severe) at 12 weeks (INSIGHT-algorithm 22.8%; EDITION 20.6%). No between-treatment differences in severe hypoglycemia were noted (1 INSIGHT-algorithm vs. 3 EDITION). The percentages of patients achieving A1c ≤7% was 28.7% (INSIGHT-algorithm) vs. 28.4% (EDITION) with similar mean A1c (SD) of 7.6% (0.9) at week 12. Similar number of patients experienced nocturnal hypoglycemia (INSIGHT-algorithm 28.7%; EDITION 27.5%). In conclusion, application of a self-titration of 1 U/day algorithm with GLA-300 resulted in a good safety profile, and was effective and comparable to the previously tested EDITION-algorithm. Funding: Study funded by Sanofi. 129 Hypoglycemia as a Function of HbA1c in Type 2 Diabetes (T2DM): Insulin Glargine 300 U/mL in a Patient-Level MetaAnalysis of EDITION 1, 2 and 3 JEAN-FRANÇOIS YALE*, RICCARDO C. BONADONNA, CLAIRE BRULLE-WOHLHUETER, EMMANUELLE BOËLLE-LE CORFEC, PRATIK CHOUDHARY, TIMOTHY S. BAILEY Montreal, QC Basal insulin therapy can be a compromise between achieving glycemic targets and avoiding hypoglycemia, dependent on how intensively insulin is titrated. In the phase 3a EDITION 1, 2 and 3 studies, insulin glargine 300 U/mL (Gla-300) provided equivalent glycemic control to insulin glargine 100 U/mL (Gla-100) with less
S47
hypoglycemia in people with T2DM. The objective of the current analysis was to evaluate rates of confirmed (≤3.9 mmol/L) or severe hypoglycemia over 6 months of treatment with Gla-300 or Gla100 in these EDITION studies, as a function of HbA1c. Meta-analysis was performed on patient-level data, and annualized hypoglycemia rate as a function of HbA1c at Month 6 was fitted using a negative binomial regression model. Adding a treatment-by-HbA1c interaction term to the model did not significantly improve the goodness of fit (interaction p-value 0.937 and 0.829 for anytime [24 h] and nocturnal [00:00 to 05:59 h] hypoglycemia, respectively). Therefore the model without interaction describes the data accurately: people treated with Gla-300 experienced a consistently lower rate of confirmed (≤3.9 mmol/L) or severe hypoglycemia vs. those treated with Gla-100, regardless of HbA1c at Month 6 (Figure). In conclusion, these results suggest that treatment with Gla 300 vs. Gla100 could allow people with T2DM to achieve equivalent glycemic control with less hypoglycemia. Funding: Study supported by Sanofi (NCT01499082, NCT01499095, NCT01676220).
130 Glycemic Control and Hypoglycemia Benefits with Insulin Glargine 300 U/mL (Gla-300) Extend to People with Type 2 Diabetes and Mild-to-Moderate Renal Impairment PETER A. SENIOR*, JAVIER ESCALADA, SERGE HALIMI, MIREILLE BONNEMAIRE, ANNA M.G. CALI, SOAZIG CHEVALIER, JANAKA KARALLIEDDE, ROBERT A. RITZEL Edmonton, AB EDITION 1, 2 and 3 showed that over 6 months, Gla-300 provided comparable glycemic control to glargine 100 U/mL (Gla-100) and less hypoglycemia in people with T2DM. Renal impairment increases the risk of hypoglycemia in people with type 2 diabetes (T2DM). The effects of Gla-300 vs. Gla-100 on HbA1c reduction and hypoglycemia were assessed in renal function subgroups (baseline eGFR ≥30 to <60, ≥60 to <90 and ≥90 mL/min/1.73 m2) in a post hoc patient-level metaanalysis of data from EDITION 1, 2 and 3. Most participants (56%) had baseline eGFR ≥60 to <90 mL/min/1.73 m2 (Table). Non-inferiority for HbA1c reduction (defined in the EDITION studies) was shown for Gla-300 and Gla-100 regardless of renal function; no evidence of heterogeneity of treatment effect was demonstrated across subgroups (p=0.46; Table 1). Risk of confirmed (≤3.9 mmol/L) or severe hypoglycemia was significantly lower for nocturnal events and comparable or lower for anytime (24 h) events for Gla-300 vs. Gla-100 across subgroups. Renal function did not affect the lower rate of nocturnal or any time hypoglycemia (no evidence of heterogeneity of treatment effect across subgroups: p=0.73, p=0.27). Gla-300 provided comparable glycemic control and consistently reduced nocturnal hypoglycemia vs. Gla-100 in participants with T2DM regardless of renal function, with no increase in any time hypoglycemia. Funding: Study funded by Sanofi (NCT01499082, NCT01499095, NCT01676220).