- Email: [email protected]
A reduced risk of hypoglycaemia with insulin degludec vs. insulin glargine U100 in Asian insulin-naïve patients with T2D
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211
T2D is an epidemic disease in Asia, with younger age and lower BMI at diagnosis in Asian vs non-Asian patients. This subject-level analysis compared clinical outcomes in Asian and non-Asian patients with T2D from 16 RCTs (target FPG ≤100 mg/dL, ≥24-week duration) adding insulin glargine 100 U/ mL (Gla-100) to OADs. Data were compared overall and by concomitant OAD therapy at baseline and Week 24. Of 3,586 participants, 235 were Asian. Patients received either metformin (MET) (n = 76), MET plus sulfonylurea (SU) (n = 111), SU (n = 16) or other OADs (n = 32). At baseline, compared with non-Asian patients, Asians were younger (53.7 vs 57.9 years; P < 0.001), had lower BMI (27.1 vs 30.8 kg/m2; P < 0.001) and FPG (169 vs 194 mg/dL; P < 0.001), but had similar diabetes duration (8.9 years) and HbA1c (8.6% vs 8.7%; P = 0.08). Mean baseline fasting C-peptide was available for 104 (44%) Asian and 2,082 (62%) non-Asian patients and was lower for Asian patients (0.95 vs 1.18 nmol/L; P < 0.001). Pearson correlation indicated a clear association of low Cpeptide level with low BMI in both Asian and Non-Asian patients (both P < 0.001); this was most prominent in Asian patients. After 24 weeks of treatment, Asian patients had a smaller HbA1c reduction (−1.30% vs −1.55%; P < 0.001), a higher overall endpoint HbA1c (7.42% vs 7.16%; P < 0.001), and a lower proportion of Asian patients achieved HbA1c ≤7.0% (40% vs 47%; P = 0.002). FPG reductions were similar in Asian and nonAsian patients (−78 vs −75 mg/dL; P = 0.27) with numerically more Asian patients reaching FPG ≤ 100 mg/dL (48% vs 34%; P = 0.21). Final daily insulin dose (0.47 vs 0.45 U/kg; P = 0.16) and hypoglycemia incidences (45% vs 47%) and event rates (5.3 vs 5.7 episodes/patient-year, PG < 70 mg/dL) were comparable in Asian and non-Asian patients. Asian patients had less weight gain (1.3 vs 1.9 kg; P = 0.01). Parameters of glycemic control and weight change were consistently more favorable in the Gla-100 + MET vs Gla-100 + MET + SU treated group, with similar estimated treatment differences between Asian vs non-Asian patients, as observed in the overall treatment groups. However, final insulin doses were higher in the Gla100 + MET group for Asians (0.57 U/kg) and non-Asians (0.50 U/ kg; P = 0.040 between groups) compared with corresponding MET + SU subgroups (Asian: 0.36 U/kg vs non-Asian: 0.41 U/kg; P = 0.045). At similar Gla-100 doses and hypoglycemia risk, overall glycemic control was worse in Asian than in non-Asian patients, suggesting higher daily insulin doses or additional antidiabetes drugs are needed for adequate glycemic control. PD-76 A reduced risk of hypoglycaemia with insulin degludec vs. insulin glargine U100 in Asian insulin-naïve patients with T2D Wenying YANG1, Qiang LI2, Zhengfang LI3, Jin-Kui YANG4, Shandong YE5 *, Charlotte HANSEN6, Hongfei XU7, Changyu PAN8. 1China-Japan Friendship Hospital, Beijing, 2The Second Affiliated Hospital of Harbin Medical University, Harbin, 3The Second Affiliated Hospital of Kunming Medical University, Kunming, 4 Beijing Tongren Hospital, Capital Medical University, Beijing, 5 Anhui Provincial Hospital, Anhui, China; 6Novo Nordisk A/S, Søborg, Denmark; 7Novo Nordisk Pharmaceuticals, 8Chinese PLA General Hospital, Beijing, China Background and aims: Insulin degludec (IDeg) is a basal insulin with a long and stable glucose-lowering effect with low withinpatient variability. A previous, global, pre-planned patientlevel meta-analysis of phase 3a trials showed IDeg was associated with significantly lower rates of overall confirmed, nocturnal confirmed, and severe hypoglycaemia vs. insulin glargine U100 (IGlar U100) in insulin-naïve patients with type 2 diabetes (T2D). This pan-Asian post-hoc meta-analysis compared the rates of hypoglycaemia with IDeg and IGlar U100 in Asian insulin-naïve patients with T2D.
S115
Methods: This Asian patient-level meta-analysis included two 26-week open-label, phase 3a, randomised, treat-to-target trials; BEGIN ONCE ASIA, and the China cohort of BEGIN ONCE representing all insulin-naïve Asian participants of the IDeg phase 3a clinical trial programme with T2D (excluding the BEGIN Flex trials). Both compared once-daily (OD) IDeg (n = 662 [BEGIN ONCE ASIA, n = 289; BEGIN ONCE-China cohort, n = 373]) and OD IGlar U100 (n = 333 [BEGIN ONCE ASIA, n = 146; BEGIN ONCE-China cohort, n = 187]). Trial maintenance period was defined as after 16 weeks of treatment. Confirmed hypoglycaemia was defined as severe episodes (requiring assistance), or plasma glucose confirmed <3.1 mmol/L. Nocturnal confirmed hypoglycaemia included confirmed episodes with onset between 00.01 and 05.59, both inclusive. Results: Similar glycaemic control was achieved at end-oftrial; IDeg was non-inferior to IGlar in terms of HbA1c reduction in the individual trial populations, with end-oftrial means of 7.2% and 7.1% respectively (BEGIN ONCE ASIA) and 6.9% and 7.0% respectively (BEGIN ONCE-China cohort). Compared with IGlar U100, treatment with IDeg resulted in a significant 24% lower rate of confirmed hypoglycaemic episodes during the total trial period (rate ratio (RR) 0.76 [0.59; 0.97]95% CI), increasing to a 30% lower rate during the maintenance period (RR 0.70 [0.50; 0.99] 95% CI). Furthermore, there was a significant 43% lower rate of nocturnal confirmed hypoglycaemic episodes with IDeg during the total trial period (RR 0.57 [0.37; 0.87] 95% CI) and a numerically 41% lower rate during the maintenance period (RR 0.59 [0.32; 1.08] 95% CI) compared with IGlar. Only two episodes of severe hypoglycaemia occurred (both with IGlar U100), hence no statistical analysis was performed. Conclusion: In Asian insulin-naïve patients with T2D, IDeg OD had significant hypoglycaemia benefits compared with IGlar U100, consistent with the findings of the global pre-planned meta-analysis. Clinically relevant reductions in both overall confirmed and nocturnal confirmed hypoglycaemia could lead to further improvement in the treatment of T2D. PD-77 Sequential changes in clinical findings of diabetic patients by replacing insulin glargine with degludec Yoshiro KATO1*, Hideki KAMIYA1, Shin TSUNEKAWA1, Masaki KONDO1, Tatsuhito HIMENO1, Yuichiro YAMADA1, Toshihito ANDO1, Saeko ASANO1, Hiromi SHIMODA1, Koichi KATO2, Jiro NAKAMURA1. 1Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 2Laboratory of Medicine, Aichi Gakuin University School of Pharmacy, Japan Background: Insulin degludec (Deg) has the different characteristics from those of insulin glargine (Gla). However, the changes in clinical findings of patients by replacing Gla with Deg has been rarely investigated by using continuous glucose monitoring (CGM). Purpose: This study was aimed at investigating how the replacement of Gla with Deg affects the clinical findings of diabetic patients by CGM. Methods: A total of 26 diabetic outpatients enrolled in this study comprised 17 type 1 diabetic patients (male/female: 4/13, age: 53.9 ± 14.2 years, HbA1c: 7.7 ± 0.9%) and 9 type 2 diabetic patients (male/female: 6/3, age: 64.9 ± 7.4 years, HbA1c: 7.3 ± 0.6%). In 17 type 1 diabetic patients, Gla was given twice a day in 14 patients and once a day in 3 patients. In 9 type 2 diabetic patients, 7 received intensive insulin therapy and 2 were given basal insulin therapy. After replacing Gla with Deg administered once a day, the mean and standard deviation (SD) of blood glucose levels (BG), frequency of hypoglycemia (<70 mg/dL) for a day and at night (0–6 a.m.) were sequentially measured by CGM.
T2D is an epidemic disease in Asia, with younger age and lower BMI at diagnosis in Asian vs non-Asian patients. This subject-level analysis compared clinical outcomes in Asian and non-Asian patients with T2D from 16 RCTs (target FPG ≤100 mg/dL, ≥24-week duration) adding insulin glargine 100 U/ mL (Gla-100) to OADs. Data were compared overall and by concomitant OAD therapy at baseline and Week 24. Of 3,586 participants, 235 were Asian. Patients received either metformin (MET) (n = 76), MET plus sulfonylurea (SU) (n = 111), SU (n = 16) or other OADs (n = 32). At baseline, compared with non-Asian patients, Asians were younger (53.7 vs 57.9 years; P < 0.001), had lower BMI (27.1 vs 30.8 kg/m2; P < 0.001) and FPG (169 vs 194 mg/dL; P < 0.001), but had similar diabetes duration (8.9 years) and HbA1c (8.6% vs 8.7%; P = 0.08). Mean baseline fasting C-peptide was available for 104 (44%) Asian and 2,082 (62%) non-Asian patients and was lower for Asian patients (0.95 vs 1.18 nmol/L; P < 0.001). Pearson correlation indicated a clear association of low Cpeptide level with low BMI in both Asian and Non-Asian patients (both P < 0.001); this was most prominent in Asian patients. After 24 weeks of treatment, Asian patients had a smaller HbA1c reduction (−1.30% vs −1.55%; P < 0.001), a higher overall endpoint HbA1c (7.42% vs 7.16%; P < 0.001), and a lower proportion of Asian patients achieved HbA1c ≤7.0% (40% vs 47%; P = 0.002). FPG reductions were similar in Asian and nonAsian patients (−78 vs −75 mg/dL; P = 0.27) with numerically more Asian patients reaching FPG ≤ 100 mg/dL (48% vs 34%; P = 0.21). Final daily insulin dose (0.47 vs 0.45 U/kg; P = 0.16) and hypoglycemia incidences (45% vs 47%) and event rates (5.3 vs 5.7 episodes/patient-year, PG < 70 mg/dL) were comparable in Asian and non-Asian patients. Asian patients had less weight gain (1.3 vs 1.9 kg; P = 0.01). Parameters of glycemic control and weight change were consistently more favorable in the Gla-100 + MET vs Gla-100 + MET + SU treated group, with similar estimated treatment differences between Asian vs non-Asian patients, as observed in the overall treatment groups. However, final insulin doses were higher in the Gla100 + MET group for Asians (0.57 U/kg) and non-Asians (0.50 U/ kg; P = 0.040 between groups) compared with corresponding MET + SU subgroups (Asian: 0.36 U/kg vs non-Asian: 0.41 U/kg; P = 0.045). At similar Gla-100 doses and hypoglycemia risk, overall glycemic control was worse in Asian than in non-Asian patients, suggesting higher daily insulin doses or additional antidiabetes drugs are needed for adequate glycemic control. PD-76 A reduced risk of hypoglycaemia with insulin degludec vs. insulin glargine U100 in Asian insulin-naïve patients with T2D Wenying YANG1, Qiang LI2, Zhengfang LI3, Jin-Kui YANG4, Shandong YE5 *, Charlotte HANSEN6, Hongfei XU7, Changyu PAN8. 1China-Japan Friendship Hospital, Beijing, 2The Second Affiliated Hospital of Harbin Medical University, Harbin, 3The Second Affiliated Hospital of Kunming Medical University, Kunming, 4 Beijing Tongren Hospital, Capital Medical University, Beijing, 5 Anhui Provincial Hospital, Anhui, China; 6Novo Nordisk A/S, Søborg, Denmark; 7Novo Nordisk Pharmaceuticals, 8Chinese PLA General Hospital, Beijing, China Background and aims: Insulin degludec (IDeg) is a basal insulin with a long and stable glucose-lowering effect with low withinpatient variability. A previous, global, pre-planned patientlevel meta-analysis of phase 3a trials showed IDeg was associated with significantly lower rates of overall confirmed, nocturnal confirmed, and severe hypoglycaemia vs. insulin glargine U100 (IGlar U100) in insulin-naïve patients with type 2 diabetes (T2D). This pan-Asian post-hoc meta-analysis compared the rates of hypoglycaemia with IDeg and IGlar U100 in Asian insulin-naïve patients with T2D.
S115
Methods: This Asian patient-level meta-analysis included two 26-week open-label, phase 3a, randomised, treat-to-target trials; BEGIN ONCE ASIA, and the China cohort of BEGIN ONCE representing all insulin-naïve Asian participants of the IDeg phase 3a clinical trial programme with T2D (excluding the BEGIN Flex trials). Both compared once-daily (OD) IDeg (n = 662 [BEGIN ONCE ASIA, n = 289; BEGIN ONCE-China cohort, n = 373]) and OD IGlar U100 (n = 333 [BEGIN ONCE ASIA, n = 146; BEGIN ONCE-China cohort, n = 187]). Trial maintenance period was defined as after 16 weeks of treatment. Confirmed hypoglycaemia was defined as severe episodes (requiring assistance), or plasma glucose confirmed <3.1 mmol/L. Nocturnal confirmed hypoglycaemia included confirmed episodes with onset between 00.01 and 05.59, both inclusive. Results: Similar glycaemic control was achieved at end-oftrial; IDeg was non-inferior to IGlar in terms of HbA1c reduction in the individual trial populations, with end-oftrial means of 7.2% and 7.1% respectively (BEGIN ONCE ASIA) and 6.9% and 7.0% respectively (BEGIN ONCE-China cohort). Compared with IGlar U100, treatment with IDeg resulted in a significant 24% lower rate of confirmed hypoglycaemic episodes during the total trial period (rate ratio (RR) 0.76 [0.59; 0.97]95% CI), increasing to a 30% lower rate during the maintenance period (RR 0.70 [0.50; 0.99] 95% CI). Furthermore, there was a significant 43% lower rate of nocturnal confirmed hypoglycaemic episodes with IDeg during the total trial period (RR 0.57 [0.37; 0.87] 95% CI) and a numerically 41% lower rate during the maintenance period (RR 0.59 [0.32; 1.08] 95% CI) compared with IGlar. Only two episodes of severe hypoglycaemia occurred (both with IGlar U100), hence no statistical analysis was performed. Conclusion: In Asian insulin-naïve patients with T2D, IDeg OD had significant hypoglycaemia benefits compared with IGlar U100, consistent with the findings of the global pre-planned meta-analysis. Clinically relevant reductions in both overall confirmed and nocturnal confirmed hypoglycaemia could lead to further improvement in the treatment of T2D. PD-77 Sequential changes in clinical findings of diabetic patients by replacing insulin glargine with degludec Yoshiro KATO1*, Hideki KAMIYA1, Shin TSUNEKAWA1, Masaki KONDO1, Tatsuhito HIMENO1, Yuichiro YAMADA1, Toshihito ANDO1, Saeko ASANO1, Hiromi SHIMODA1, Koichi KATO2, Jiro NAKAMURA1. 1Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 2Laboratory of Medicine, Aichi Gakuin University School of Pharmacy, Japan Background: Insulin degludec (Deg) has the different characteristics from those of insulin glargine (Gla). However, the changes in clinical findings of patients by replacing Gla with Deg has been rarely investigated by using continuous glucose monitoring (CGM). Purpose: This study was aimed at investigating how the replacement of Gla with Deg affects the clinical findings of diabetic patients by CGM. Methods: A total of 26 diabetic outpatients enrolled in this study comprised 17 type 1 diabetic patients (male/female: 4/13, age: 53.9 ± 14.2 years, HbA1c: 7.7 ± 0.9%) and 9 type 2 diabetic patients (male/female: 6/3, age: 64.9 ± 7.4 years, HbA1c: 7.3 ± 0.6%). In 17 type 1 diabetic patients, Gla was given twice a day in 14 patients and once a day in 3 patients. In 9 type 2 diabetic patients, 7 received intensive insulin therapy and 2 were given basal insulin therapy. After replacing Gla with Deg administered once a day, the mean and standard deviation (SD) of blood glucose levels (BG), frequency of hypoglycemia (<70 mg/dL) for a day and at night (0–6 a.m.) were sequentially measured by CGM.