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Efficacy and Cardiovascular (CV) Safety of Linagliptin as Add-on to Insulin in Type 2 Diabetes (T2D)—A Pooled Comprehensive Post-Hoc Analysis
Abstracts / Can J Diabetes 38 (2014) S29eS74
153 withdrawn
154 Efficacy and Cardiovascular (CV) Safety of Linagliptin as Add-on to Insulin in Type 2 Diabetes (T2D)dA Pooled Comprehensive Post-Hoc Analysis BERNARD ZINMAN, BO AHRÉN, DIETMAR NEUBACHER, SANJAY PATEL, ODD ERIK JOHANSEN, HANS J. WOERLE Toronto, ON; Lund, Sweden; Ingelheim, Germany; Bracknell, Berkshire, UK; Asker, Norway; Ingelheim, Germany Combination of a DPP-4 inhibitor with insulin is a novel glucose-lowering strategy in T2D. We assessed the efficacy and CV safety of linagliptin (LINA) as add-on to insulin (basal only or basal/bolus) in 1613 patients enrolled in 4 randomized, controlled trials, lasting 6e18 months. Glycemia, lipid profile, blood pressure (BP) and heart rate (HR) were assessed as change from baseline to last available value. Hypoglycemia was collected as investigator reported adverse events while CV events and overall mortality were prospectively and independently adjudicated. Linagliptin when added to insulin reduced HbA1c significantly as compared to comparator (e0.11.0, e0.51.0; p<0.001; comparators, LINA respectively) and also provided a relative weight benefit (+0.63.5 kg vs. e0.14.5 kg; p¼0.0024; comparators vs. LINA respectively) and reduced insulin requirement (+2.313 vs. 0.715.7; p¼0.0189;
S57
comparators vs. LINA respectively) without affecting lipids, BP or HR (data not shown). Incidence of hypoglycemia, including confirmed with plasma glucose 3.9 mmol/L, or severe hypoglycaemia, did not increase. Incidence rates of the composite of CV death, myocardial infarction, stroke and hospitalization for unstable angina (4P-MACE) was w 3%/year, without between-group differences. Linagliptin, when added to ongoing insulin-treatment, provided a beneficial impact on efficacy parameters and had a neutral impact on 4P-MACE and total mortality. The ongoing CAROLINA and CARMELINA trials will provide further insights into this combination.
155 Efficacy and Safety of Empagliflozin (EMPA) in Younger, Overweight/Obese Patients with Type 2 Diabetes (T2DM) with HbA1c ‡8% LUDWIG MERKER, SOEREN S. LUND, STEFAN HANTEL, AFSHIN SALSALI, GABRIEL KIM, ULI BROEDL, HANS J. WOERLE, THOMAS HACH Dormagen, Germany; Ingelheim Am Rhein, Germany; Biberach, Germany In a pooled analysis of 4 randomized phase III trials in patients with T2DM aged >18 years with body mass index (BMI) 45 kg/m2 and HbA1c 7 and 10% (n¼2477), EMPA 10 mg and EMPA 25 mg for 24 weeks as monotherapy or add-on therapy showed more
Table Baseline demographics, clinical characteristics, and impact on efficacy/safety parameters from baseline to last treatment. Data given as mean ± SD
Characteristics Age (years), mean SD Male/ Female, % BMI, kg/m2 Race (White/Black/Asian), % Diabetes duration > 5 years , % CV risk factors and CV medications Current smoker, % Urinary albumine-creatinine ratio (mg/g), % Microalbuminuria (30e300) Macroalbuminuria ( 300) Coronary artery disease/cerebrovascular disease,% Hypertension,% Statins/ASA,% Exposure to therapy Median days (min, max) Patient years (cumulative) Impact on HbA1c, insulin requirement, weight and hypoglycemia HbA1c, % Baseline Change from baseline to end of treatment Insulin, U Basal insulin, % Baseline dose Change from baseline to end of treatment Weight, kg Baseline Change from baseline to end of treatment Hypoglycemia, n (%) patients exhibiting at least 1 event Any asymptomatic or symptomatic hypoglycemia
Comparator (n[802)
Linagliptin (n[811)
6210 54.5/45.5 31.45.2 79/6/15 89.3
6210 55.2/44.8 31.15.6 80/7/13 86.6
13.3 25.4 17.0
14.9 30.3 13.6
24.1/8.6 82.9 58.5/55.1
23.7/9.0 82.9 55.1/57.5
371 (1e707) 863
372 (1e712) 899 Statistical evaluation
8.30.9 e0.11.0
8.30.9 e0.51.0
p<0.001
85.8% 4639 2.313.0
86.2% 4838 0.715.7
p¼0.0189
86.218.9 0.63.5
85.919.3 e0.14.5
p¼0.0024
316 (39.4)
314 (38.7)
Any severe# or symptomatic hypoglycemia with PG 70 mg/dL Any severe# or symptomatic hypoglycemia with PG <54 mg/dL
237 (29.6) 135 (16.8)
221 (27.3) 128 (15.8)
Any severe# hypoglycemia Adjudicated CV events/mortality 4P-MACE** Incidence rate per 1000 pat years/n
17 (2.1)
23 (2.8)
27.5/24
29.8/27
HR 1.07*** (0.62, 1.85)
9.1/8
8.8/8
HR 0.96*** (0.36, 2.57)
Overall mortality Incidence rate per 1000 pat years/n
OR 0.99* (0.81, 1.23) OR 0.95* (0.73, 1.24)
#: Severe hypoglycemia defined as an event requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions. *: Odds ratio by logistic regression model, **: a composite endpoint of CV death, myocardial infarction, stroke and hospitalization for unstable angina pectoris; ***: Hazard ratio by Cox proportional model.
153 withdrawn
154 Efficacy and Cardiovascular (CV) Safety of Linagliptin as Add-on to Insulin in Type 2 Diabetes (T2D)dA Pooled Comprehensive Post-Hoc Analysis BERNARD ZINMAN, BO AHRÉN, DIETMAR NEUBACHER, SANJAY PATEL, ODD ERIK JOHANSEN, HANS J. WOERLE Toronto, ON; Lund, Sweden; Ingelheim, Germany; Bracknell, Berkshire, UK; Asker, Norway; Ingelheim, Germany Combination of a DPP-4 inhibitor with insulin is a novel glucose-lowering strategy in T2D. We assessed the efficacy and CV safety of linagliptin (LINA) as add-on to insulin (basal only or basal/bolus) in 1613 patients enrolled in 4 randomized, controlled trials, lasting 6e18 months. Glycemia, lipid profile, blood pressure (BP) and heart rate (HR) were assessed as change from baseline to last available value. Hypoglycemia was collected as investigator reported adverse events while CV events and overall mortality were prospectively and independently adjudicated. Linagliptin when added to insulin reduced HbA1c significantly as compared to comparator (e0.11.0, e0.51.0; p<0.001; comparators, LINA respectively) and also provided a relative weight benefit (+0.63.5 kg vs. e0.14.5 kg; p¼0.0024; comparators vs. LINA respectively) and reduced insulin requirement (+2.313 vs. 0.715.7; p¼0.0189;
S57
comparators vs. LINA respectively) without affecting lipids, BP or HR (data not shown). Incidence of hypoglycemia, including confirmed with plasma glucose 3.9 mmol/L, or severe hypoglycaemia, did not increase. Incidence rates of the composite of CV death, myocardial infarction, stroke and hospitalization for unstable angina (4P-MACE) was w 3%/year, without between-group differences. Linagliptin, when added to ongoing insulin-treatment, provided a beneficial impact on efficacy parameters and had a neutral impact on 4P-MACE and total mortality. The ongoing CAROLINA and CARMELINA trials will provide further insights into this combination.
155 Efficacy and Safety of Empagliflozin (EMPA) in Younger, Overweight/Obese Patients with Type 2 Diabetes (T2DM) with HbA1c ‡8% LUDWIG MERKER, SOEREN S. LUND, STEFAN HANTEL, AFSHIN SALSALI, GABRIEL KIM, ULI BROEDL, HANS J. WOERLE, THOMAS HACH Dormagen, Germany; Ingelheim Am Rhein, Germany; Biberach, Germany In a pooled analysis of 4 randomized phase III trials in patients with T2DM aged >18 years with body mass index (BMI) 45 kg/m2 and HbA1c 7 and 10% (n¼2477), EMPA 10 mg and EMPA 25 mg for 24 weeks as monotherapy or add-on therapy showed more
Table Baseline demographics, clinical characteristics, and impact on efficacy/safety parameters from baseline to last treatment. Data given as mean ± SD
Characteristics Age (years), mean SD Male/ Female, % BMI, kg/m2 Race (White/Black/Asian), % Diabetes duration > 5 years , % CV risk factors and CV medications Current smoker, % Urinary albumine-creatinine ratio (mg/g), % Microalbuminuria (30e300) Macroalbuminuria ( 300) Coronary artery disease/cerebrovascular disease,% Hypertension,% Statins/ASA,% Exposure to therapy Median days (min, max) Patient years (cumulative) Impact on HbA1c, insulin requirement, weight and hypoglycemia HbA1c, % Baseline Change from baseline to end of treatment Insulin, U Basal insulin, % Baseline dose Change from baseline to end of treatment Weight, kg Baseline Change from baseline to end of treatment Hypoglycemia, n (%) patients exhibiting at least 1 event Any asymptomatic or symptomatic hypoglycemia
Comparator (n[802)
Linagliptin (n[811)
6210 54.5/45.5 31.45.2 79/6/15 89.3
6210 55.2/44.8 31.15.6 80/7/13 86.6
13.3 25.4 17.0
14.9 30.3 13.6
24.1/8.6 82.9 58.5/55.1
23.7/9.0 82.9 55.1/57.5
371 (1e707) 863
372 (1e712) 899 Statistical evaluation
8.30.9 e0.11.0
8.30.9 e0.51.0
p<0.001
85.8% 4639 2.313.0
86.2% 4838 0.715.7
p¼0.0189
86.218.9 0.63.5
85.919.3 e0.14.5
p¼0.0024
316 (39.4)
314 (38.7)
Any severe# or symptomatic hypoglycemia with PG 70 mg/dL Any severe# or symptomatic hypoglycemia with PG <54 mg/dL
237 (29.6) 135 (16.8)
221 (27.3) 128 (15.8)
Any severe# hypoglycemia Adjudicated CV events/mortality 4P-MACE** Incidence rate per 1000 pat years/n
17 (2.1)
23 (2.8)
27.5/24
29.8/27
HR 1.07*** (0.62, 1.85)
9.1/8
8.8/8
HR 0.96*** (0.36, 2.57)
Overall mortality Incidence rate per 1000 pat years/n
OR 0.99* (0.81, 1.23) OR 0.95* (0.73, 1.24)
#: Severe hypoglycemia defined as an event requiring the assistance of another person to actively administer carbohydrate, glucagon or other resuscitative actions. *: Odds ratio by logistic regression model, **: a composite endpoint of CV death, myocardial infarction, stroke and hospitalization for unstable angina pectoris; ***: Hazard ratio by Cox proportional model.