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– Other Antihyperglycemic Agents in Type 2 Diabetes
S28
Abstracts / Can J Diabetes 37 (2013) S13eS84
of previous exposure to insulin, patients with high A1c level showed lower contribution from PPG compared to patients with low A1c level. Conclusion: In patients with A1c˂8.5, PPG contribution to hyperglycemia is higher than in patients with A1c8.5. In IT patients, PPG contribution accounts for approximately 50% of hyperglycemia. These findings suggest that depending on the A1c level and whether a T2DM patient is IN or IT, an individualized approach should be considered for initiating or intensifying treatment if they are above the A1c target of 7%.
73 Effects of Canagliflozin Added on to Basal Insulin +/e Other Antihyperglycemic Agents in Type 2 Diabetes RICHARD DUMAS*, MELANIE DAVIES, JULIO ROSENSTOCK, MEHUL DESAI, MARIA ALBA, GEORGE CAPUANO, GARY MEININGER Laval, QC; Leicester, UK; Dallas, TX; Raritan, NJ Purpose: Evaluate effects of canagliflozin (CANA) added on to basal insulin +/e other antihyperglycemic agents in type 2 diabetes. Method: An exploratory analysis from the CANagliflozin cardioVascular Assessment Study (CANVAS; in T2DM with a history or high risk of cardiovascular disease) evaluated CANA 100 mg and 300 mg versus placebo (PBO) in a subset of subjects in the insulin substudy on stable, non-titrated basal (but not prandial) insulin (30 IU/day basal insulin at study entry) +/e other antihyperglycemic agents. Results: Subjects (n¼278) had a baseline mean age of 63 years; A1C 8.3%; fasting plasma glucose (FPG) 8.82 mmol/L; BMI 34.4 kg/m2 and insulin dose 59 IU/day. At week 18, relative to placebo CANA 100 mg and 300 mg reduced A1C (e0.86% and e0.89%); FPG (by 1.39 and 1.72 mmol/L) and body weight (by 1.8% and 2.7%) (Table 1). Post-baseline daily insulin dose (prior to glycemic rescue) was unchanged for 93% of PBO-treated subjects versus 85% and 86% of subjects with CANA 100 mg and 300 mg (mostly dose reductions with CANA). Overall AE, AE-related discontinuation and serious AE rates were higher with CANA than PBO. The proportion of subjects with documented hypoglycemia (3.9 mmol/L or severe events) was higher with CANA 100 mg and 300 mg than PBO (42%, 43%, 25%, respectively), with severe hypoglycemia rates of 0%, 1% and 2%, respectively.
Summary: In subjects with T2DM, CANA added on to basal insulin improved glycemic control, reduced body weight and was generally well tolerated, with some increase in hypoglycemia risk at 18 weeks.
74 Efficacy and Safety of Lixisenatide in Elderly Type 2 Diabetes Mellitus Patients: Subanalysis from the GetGoal Program RICHARD DUMAS*, MARKOLF HANEFELD, RACHELE BERRIA, JAY LIN, RONNIE ARONSON, PATRICE DARMON, MARC EVANS, LUC VAN GAAL Laval, QC; Dresden, Germany; Bridgewater, NJ; Flemington, NJ; Toronto, ON; Marseille, France; Llandough, UK; Antwerp, Belgium Aims: To evaluate the safety and efficacy of the novel once-daily prandial glucagon-like peptide-1 receptor agonist lixisenatide* as an add on to oral antihyperglycemic agents in elderly patients with type 2 diabetes mellitus (T2DM). Methods: This was a meta-analysis of 501 elderly patients (65 years of age) with T2DM from 5 phase III, randomized, controlled trials from the lixisenatide clinical trial program (GetGoaleM, eP, eS, eMeAsia and eF1). Results: Mean baseline characteristics: age 69.4 years; body mass index 29.4 kg/m2; diabetes duration 10.6 years; A1C 8.0% (lixisenatide) and 7.9% (placebo); 90.0% of patients were on metformin, 44.7% sulfonylurea and 16.6% thiazolidinediones. After 24 weeks, lixisenatide significantly reduced A1C vs. placebo (odds ratio [95% CI]: e0.5% [e0.7, e0.4], p<0.00001) and was statistically better than placebo in each of the following composite endpoints: proportion of patients achieving A1C <7% (49.3 vs. 22.8%, p<0.0001); A1C <7% and no weight gain (41.8 vs. 18.8%, p<0.0001); A1C <7% and no documented symptomatic hypoglycemia (44.4 vs. 22.3%, p<0.0001); A1C <7%, no documented symptomatic hypoglycemia and no weight gain (37.2 vs. 18.8%, p<0.0001). A higher trend for more frequent documented symptomatic hypoglycemia was seen with lixisenatide compared with placebo (odds ratio [95% CI]: 2.1 [0.9, 5.0] p¼0.09), mainly driven by sulfonylurea as background medication. There were no cases of severe hypoglycemia in either group.
Table 1 Summary of Efficacy (mITT, LOCF) and Safety (Safety Population) Endpoints at Week 18 (Basal Insulin Subset) PBO (n¼88) Efficacy Parameter* A1C baseline, % Change Difference vs. PBO FPG baseline, mmol/L Change Difference vs. PBO Body weight baseline, kg % change Difference vs. PBO Safety Parameter, n (%) Any AE AE leading to discontinuation AE related to study drug Serious AE
8.3 0.8 0.10 0.08 8.77 2.86 0.33 0.27 102.3 22.9 0.0 0.3
47 1 14 3
(53.4) (1.1) (15.9) (3.4)
CANA 100 mg (n¼86)
CANA 300 mg (n¼104)
8.4 0.9 e0.76 0.08 e0.86 (e1.07, e0.65) 8.79 2.21 e1.04 0.27 e1.37 (e2.08, e0.66) 97.5 23.7 e1.8 0.3 e1.8 (e2.7, e0.9)
8.2 0.8 e0.79 0.07 e0.89 (e1.09, e0.69) 8.51 2.24 e1.37 0.25 e1.71 (e2.39, e1.03) 99.2 20.2 e2.7 0.3 e2.7 (e3.6, e1.8)
53 3 19 6
(61.6) (3.5) (22.1) (7.0)
70 7 41 9
(67.3) (6.7) (39.4) (8.7)
mITT, modified intent to treat; LOCF, last observation carried forward; SD, standard deviation; LS, least squares; SE, standard error; ANCOVA, analysis of covariance; CI, confidence interval. * Mean SD baseline value, LS mean SE change from baseline using ANCOVA, and PBO-subtracted LS mean (95% CI) value.
Abstracts / Can J Diabetes 37 (2013) S13eS84
of previous exposure to insulin, patients with high A1c level showed lower contribution from PPG compared to patients with low A1c level. Conclusion: In patients with A1c˂8.5, PPG contribution to hyperglycemia is higher than in patients with A1c8.5. In IT patients, PPG contribution accounts for approximately 50% of hyperglycemia. These findings suggest that depending on the A1c level and whether a T2DM patient is IN or IT, an individualized approach should be considered for initiating or intensifying treatment if they are above the A1c target of 7%.
73 Effects of Canagliflozin Added on to Basal Insulin +/e Other Antihyperglycemic Agents in Type 2 Diabetes RICHARD DUMAS*, MELANIE DAVIES, JULIO ROSENSTOCK, MEHUL DESAI, MARIA ALBA, GEORGE CAPUANO, GARY MEININGER Laval, QC; Leicester, UK; Dallas, TX; Raritan, NJ Purpose: Evaluate effects of canagliflozin (CANA) added on to basal insulin +/e other antihyperglycemic agents in type 2 diabetes. Method: An exploratory analysis from the CANagliflozin cardioVascular Assessment Study (CANVAS; in T2DM with a history or high risk of cardiovascular disease) evaluated CANA 100 mg and 300 mg versus placebo (PBO) in a subset of subjects in the insulin substudy on stable, non-titrated basal (but not prandial) insulin (30 IU/day basal insulin at study entry) +/e other antihyperglycemic agents. Results: Subjects (n¼278) had a baseline mean age of 63 years; A1C 8.3%; fasting plasma glucose (FPG) 8.82 mmol/L; BMI 34.4 kg/m2 and insulin dose 59 IU/day. At week 18, relative to placebo CANA 100 mg and 300 mg reduced A1C (e0.86% and e0.89%); FPG (by 1.39 and 1.72 mmol/L) and body weight (by 1.8% and 2.7%) (Table 1). Post-baseline daily insulin dose (prior to glycemic rescue) was unchanged for 93% of PBO-treated subjects versus 85% and 86% of subjects with CANA 100 mg and 300 mg (mostly dose reductions with CANA). Overall AE, AE-related discontinuation and serious AE rates were higher with CANA than PBO. The proportion of subjects with documented hypoglycemia (3.9 mmol/L or severe events) was higher with CANA 100 mg and 300 mg than PBO (42%, 43%, 25%, respectively), with severe hypoglycemia rates of 0%, 1% and 2%, respectively.
Summary: In subjects with T2DM, CANA added on to basal insulin improved glycemic control, reduced body weight and was generally well tolerated, with some increase in hypoglycemia risk at 18 weeks.
74 Efficacy and Safety of Lixisenatide in Elderly Type 2 Diabetes Mellitus Patients: Subanalysis from the GetGoal Program RICHARD DUMAS*, MARKOLF HANEFELD, RACHELE BERRIA, JAY LIN, RONNIE ARONSON, PATRICE DARMON, MARC EVANS, LUC VAN GAAL Laval, QC; Dresden, Germany; Bridgewater, NJ; Flemington, NJ; Toronto, ON; Marseille, France; Llandough, UK; Antwerp, Belgium Aims: To evaluate the safety and efficacy of the novel once-daily prandial glucagon-like peptide-1 receptor agonist lixisenatide* as an add on to oral antihyperglycemic agents in elderly patients with type 2 diabetes mellitus (T2DM). Methods: This was a meta-analysis of 501 elderly patients (65 years of age) with T2DM from 5 phase III, randomized, controlled trials from the lixisenatide clinical trial program (GetGoaleM, eP, eS, eMeAsia and eF1). Results: Mean baseline characteristics: age 69.4 years; body mass index 29.4 kg/m2; diabetes duration 10.6 years; A1C 8.0% (lixisenatide) and 7.9% (placebo); 90.0% of patients were on metformin, 44.7% sulfonylurea and 16.6% thiazolidinediones. After 24 weeks, lixisenatide significantly reduced A1C vs. placebo (odds ratio [95% CI]: e0.5% [e0.7, e0.4], p<0.00001) and was statistically better than placebo in each of the following composite endpoints: proportion of patients achieving A1C <7% (49.3 vs. 22.8%, p<0.0001); A1C <7% and no weight gain (41.8 vs. 18.8%, p<0.0001); A1C <7% and no documented symptomatic hypoglycemia (44.4 vs. 22.3%, p<0.0001); A1C <7%, no documented symptomatic hypoglycemia and no weight gain (37.2 vs. 18.8%, p<0.0001). A higher trend for more frequent documented symptomatic hypoglycemia was seen with lixisenatide compared with placebo (odds ratio [95% CI]: 2.1 [0.9, 5.0] p¼0.09), mainly driven by sulfonylurea as background medication. There were no cases of severe hypoglycemia in either group.
Table 1 Summary of Efficacy (mITT, LOCF) and Safety (Safety Population) Endpoints at Week 18 (Basal Insulin Subset) PBO (n¼88) Efficacy Parameter* A1C baseline, % Change Difference vs. PBO FPG baseline, mmol/L Change Difference vs. PBO Body weight baseline, kg % change Difference vs. PBO Safety Parameter, n (%) Any AE AE leading to discontinuation AE related to study drug Serious AE
8.3 0.8 0.10 0.08 8.77 2.86 0.33 0.27 102.3 22.9 0.0 0.3
47 1 14 3
(53.4) (1.1) (15.9) (3.4)
CANA 100 mg (n¼86)
CANA 300 mg (n¼104)
8.4 0.9 e0.76 0.08 e0.86 (e1.07, e0.65) 8.79 2.21 e1.04 0.27 e1.37 (e2.08, e0.66) 97.5 23.7 e1.8 0.3 e1.8 (e2.7, e0.9)
8.2 0.8 e0.79 0.07 e0.89 (e1.09, e0.69) 8.51 2.24 e1.37 0.25 e1.71 (e2.39, e1.03) 99.2 20.2 e2.7 0.3 e2.7 (e3.6, e1.8)
53 3 19 6
(61.6) (3.5) (22.1) (7.0)
70 7 41 9
(67.3) (6.7) (39.4) (8.7)
mITT, modified intent to treat; LOCF, last observation carried forward; SD, standard deviation; LS, least squares; SE, standard error; ANCOVA, analysis of covariance; CI, confidence interval. * Mean SD baseline value, LS mean SE change from baseline using ANCOVA, and PBO-subtracted LS mean (95% CI) value.