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Nateglinide is effective and safe in elderly patients with type 2 diabetes
Track 2. Clinical Research & Care
single-centre, open-label, parallel-group study comprised three screening visits, followed by a 7-day in-patient period. Thirty-four patients (BMI 30.6 kg/m2), who had normal renal function (creatinine clearance (CLCR) > 80 ml/min; n = 12). mild-to-moderate renal dysfunction (80 ) CLca> 40 ml/mm; n = 12) or severe renal dysfunction ((&a -Z 40 ml/mm: n = lo), received a single 2 mg dose of repaglinide on Day 1, followed by preprandial 2 mg doses with main meals on Days 2 to 4, and a final 2 mg dose of repaglinide on Day 5. The pharmacokinetics of repaglinide were independent of renal function in the groups with normal or mild-to-moderate renal dysfunction. Mean AUC, terminal elimination rate constant and maximum concentration were similar for patients with mild-to moderate renal dysfunction compared with normal renal function, either following a single dose in the fasting state or after 3 days of multiple dosing. In patients with severe renal dysfunction, the main pharmacokinetic finding was a longer half-life after multiple dosing. Repaglinide was well tolerated, and rates of minor hypoglycaemia were similar in patients with severe, mild-to-moderate and no renal dysfunction. No major hypoglycaemic episodes occurred. In conclusion, patients with Type 2 diabetes and mild or moderate impairment of renal function may be treated with repaglinide without special precautions. If repaglinide is used in patients with severely impaired renal function, careful upward dosage may be necessary if indicated by blood glucose measurements.
P338 Compared with Repaglinide Sulphonylurea Treatment in Type 2 Diabetes Is Associated with a 2.5Fold Increase in Symptomatic Hypoglycaemia with Blood Glucose Levels -z 2.5 nunol/l JGRGEN SMEDEGAARD KRISTENSEN, Kirstine Brown Frandsen, Thomas Bayer, Peter Miiller. Nova Nordisk, Copenhagen, Denmark Sulphonylmea (SU) treatment is associated with the occurrence of potentially dangerous hypoglycaemia. By avoiding stimulation of insulin secretion in the fasting state, using the prandial glucose regulator repaglinide (Re), it is anticipated that the rate of major hypoglycaemia can be reduced. We have evaluated the l-year frequency of major hypoglycaemia (subjective symptoms and a concomitant BG reading < 2.5 mmohl) in four double-blind, randomised studies with identical protocols, where Type 2 patients were treated with either Re, n=761, or an SU (glibenclamide, gliclazide, or glipizide), n=367. Diet pattern consisted of three main meals at regular times, and optional snacks as prescribed by the physician. Patients were not allowed to change mealtimes or skip a meal, as data from other studies indicate that this substantially increases the hypoglycaemic risk with SU, (but not with Re). Both SU and Re were administered according to labelling: SU once or twice daily, Re before each main meal. Metabolic control (WA,,) was identical at entry (7.2%) and during each study (7.12, 7.2%, 7.4%. and 7.5%). The rate of major hypoglycaemic events was 2.5 times higher in the SU group than in the Re group (3.3% vs 1.3%. p < 0.03). There were no significant differences between the SUs. Moreover, analysis of all hypoglycaemic events with concomitant BG determination revealed that more than 50% of the events with SU had a reading < 3.3 mmol/l, whereas the opposite was the case for Re, where more than 50% of the readings were > 3.3 mmol/l. In conclusion, even when a strict diet is prescribed the use of Re is associated with a significant decrease in major hypoglycaemic events, compared with SU. This decrease is obtained without compromising overall glycaemic control.
s73
ing early insulin secretion. NAT when taken orally immediately before meals is predicted to be safe and effective Rx for the treatment of Type 2 diabetes. The prevalence of ‘lype 2 diabetes increases with increasing age and older patients are more vulnerable to hypoglycemia and other treatment-related adverse effects. This analysis was conducted to assess the utility of nateglinide monotherapy treatment for younger and older patients with Type 2 diabetes. Materials and Methods: Efficacy data from 2 similarly designed, blinded placebo controlled trials were pooled to analyze change from baseline in HbAi,. Adverse event data from 11 controlled clinical trials were pooled to assess safety and tolerability. Results: Nateglinide 120 mg produced similar reductions in HbAi, in patients below and above 65 years of age. Nateglinide 120 mg Age < 65 years
N=221
Baseline HbAlc Mean change (SD) Age t 65 years Baseline HbAlc
8.24% -0.42 (1.25) N=99 8.09%
0.31 (1.27) N=lOl
Mean change (SD)
-0.54 (0.88)
8.16%
8.07% 0.27 (0.89)
The overall incidence of adverse events and 265, respectively) and hypoglycemia 265, respectively) were similar in both Nateglinide is similarly effective and safe with Type 2 diabetes.
(62.5% and 65.5% for x65 (2.4% and 2.3% for 465 and patient groups. Conclusions: in younger and older patients
P340 Sustained Efficacy and Pulmonary Safety of Inhaled Insulin during 2 Years of Outpatient Therapy W.T. CEFALU’, C.C. Balagtas*, W.H. Landschulz’, R.A. Gelfand*. ’ Burlington, VT, United States of America: ’ Pfizer Inc, Groton, CT, United States of America Aims: Short-term clinical trials with inhaled insulin (INH) have shown encouraging efficacy and safety. We examined whether these favorable results could be maintained long-term. Methods: We offered continued INH to subjects with type 1 or type 2 diabetes who had completed any of 3 randomized, 3-month phase 2 trials (in type 1, type 2 on insulin, and type 2 failing oral agents). Treatment of this cohort is ongoing. Results: Currently available, pooled efficacy (HbAi,) and pulmonary safety results for up to 2 years are: Hemoglobin A,c (%)
MGUI SD
Baseline
12 months
18 months
24 months
8.9 1.5
8.1 1.3
8.0 1.2
8.0
145
125
83
12 months
18 months
24 months
3.1 0.8 149
3.1 0.8 125
3.1 0.8 84
24.7
24.8
24.5
6.3 131
6.1 95
6.8 64
N 145 Pulmonary function tests Baseline EVl (1) MLXl SD N
3.2 0.8 149
DLo (ml/min/mmHg) MWI 25.6 SD 6.7
P339
N
Nateglinide Is Effective and Safe in Elderly Patients with ‘ljpe 2 Diabetes S. MALLOWS, C. Guitard, Sharon Shen, M. Gatlin. Novanis Pharmaceuticals. NJ: Base1
(FEV,: Forced expiratory volume in 1 set; DLo:
Background and Aims: Nateglinide (NAT) is a fast acting, short duration insulinotropic agent which improves mealtime glucose control by enhanc-
PlaC&
N=239
131
1.2
Diffusion capacity)
Conclusions: HbAi, and pulmonary function tests this broad cohort of patients with type 1 or type years of INH therapy. These results suggest that and pulmonary safety of INH, shown previously in sustained long-term.
have been stable for 2 diabetes during 2 the clinical efficacy short-term trials, are
single-centre, open-label, parallel-group study comprised three screening visits, followed by a 7-day in-patient period. Thirty-four patients (BMI 30.6 kg/m2), who had normal renal function (creatinine clearance (CLCR) > 80 ml/min; n = 12). mild-to-moderate renal dysfunction (80 ) CLca> 40 ml/mm; n = 12) or severe renal dysfunction ((&a -Z 40 ml/mm: n = lo), received a single 2 mg dose of repaglinide on Day 1, followed by preprandial 2 mg doses with main meals on Days 2 to 4, and a final 2 mg dose of repaglinide on Day 5. The pharmacokinetics of repaglinide were independent of renal function in the groups with normal or mild-to-moderate renal dysfunction. Mean AUC, terminal elimination rate constant and maximum concentration were similar for patients with mild-to moderate renal dysfunction compared with normal renal function, either following a single dose in the fasting state or after 3 days of multiple dosing. In patients with severe renal dysfunction, the main pharmacokinetic finding was a longer half-life after multiple dosing. Repaglinide was well tolerated, and rates of minor hypoglycaemia were similar in patients with severe, mild-to-moderate and no renal dysfunction. No major hypoglycaemic episodes occurred. In conclusion, patients with Type 2 diabetes and mild or moderate impairment of renal function may be treated with repaglinide without special precautions. If repaglinide is used in patients with severely impaired renal function, careful upward dosage may be necessary if indicated by blood glucose measurements.
P338 Compared with Repaglinide Sulphonylurea Treatment in Type 2 Diabetes Is Associated with a 2.5Fold Increase in Symptomatic Hypoglycaemia with Blood Glucose Levels -z 2.5 nunol/l JGRGEN SMEDEGAARD KRISTENSEN, Kirstine Brown Frandsen, Thomas Bayer, Peter Miiller. Nova Nordisk, Copenhagen, Denmark Sulphonylmea (SU) treatment is associated with the occurrence of potentially dangerous hypoglycaemia. By avoiding stimulation of insulin secretion in the fasting state, using the prandial glucose regulator repaglinide (Re), it is anticipated that the rate of major hypoglycaemia can be reduced. We have evaluated the l-year frequency of major hypoglycaemia (subjective symptoms and a concomitant BG reading < 2.5 mmohl) in four double-blind, randomised studies with identical protocols, where Type 2 patients were treated with either Re, n=761, or an SU (glibenclamide, gliclazide, or glipizide), n=367. Diet pattern consisted of three main meals at regular times, and optional snacks as prescribed by the physician. Patients were not allowed to change mealtimes or skip a meal, as data from other studies indicate that this substantially increases the hypoglycaemic risk with SU, (but not with Re). Both SU and Re were administered according to labelling: SU once or twice daily, Re before each main meal. Metabolic control (WA,,) was identical at entry (7.2%) and during each study (7.12, 7.2%, 7.4%. and 7.5%). The rate of major hypoglycaemic events was 2.5 times higher in the SU group than in the Re group (3.3% vs 1.3%. p < 0.03). There were no significant differences between the SUs. Moreover, analysis of all hypoglycaemic events with concomitant BG determination revealed that more than 50% of the events with SU had a reading < 3.3 mmol/l, whereas the opposite was the case for Re, where more than 50% of the readings were > 3.3 mmol/l. In conclusion, even when a strict diet is prescribed the use of Re is associated with a significant decrease in major hypoglycaemic events, compared with SU. This decrease is obtained without compromising overall glycaemic control.
s73
ing early insulin secretion. NAT when taken orally immediately before meals is predicted to be safe and effective Rx for the treatment of Type 2 diabetes. The prevalence of ‘lype 2 diabetes increases with increasing age and older patients are more vulnerable to hypoglycemia and other treatment-related adverse effects. This analysis was conducted to assess the utility of nateglinide monotherapy treatment for younger and older patients with Type 2 diabetes. Materials and Methods: Efficacy data from 2 similarly designed, blinded placebo controlled trials were pooled to analyze change from baseline in HbAi,. Adverse event data from 11 controlled clinical trials were pooled to assess safety and tolerability. Results: Nateglinide 120 mg produced similar reductions in HbAi, in patients below and above 65 years of age. Nateglinide 120 mg Age < 65 years
N=221
Baseline HbAlc Mean change (SD) Age t 65 years Baseline HbAlc
8.24% -0.42 (1.25) N=99 8.09%
0.31 (1.27) N=lOl
Mean change (SD)
-0.54 (0.88)
8.16%
8.07% 0.27 (0.89)
The overall incidence of adverse events and 265, respectively) and hypoglycemia 265, respectively) were similar in both Nateglinide is similarly effective and safe with Type 2 diabetes.
(62.5% and 65.5% for x65 (2.4% and 2.3% for 465 and patient groups. Conclusions: in younger and older patients
P340 Sustained Efficacy and Pulmonary Safety of Inhaled Insulin during 2 Years of Outpatient Therapy W.T. CEFALU’, C.C. Balagtas*, W.H. Landschulz’, R.A. Gelfand*. ’ Burlington, VT, United States of America: ’ Pfizer Inc, Groton, CT, United States of America Aims: Short-term clinical trials with inhaled insulin (INH) have shown encouraging efficacy and safety. We examined whether these favorable results could be maintained long-term. Methods: We offered continued INH to subjects with type 1 or type 2 diabetes who had completed any of 3 randomized, 3-month phase 2 trials (in type 1, type 2 on insulin, and type 2 failing oral agents). Treatment of this cohort is ongoing. Results: Currently available, pooled efficacy (HbAi,) and pulmonary safety results for up to 2 years are: Hemoglobin A,c (%)
MGUI SD
Baseline
12 months
18 months
24 months
8.9 1.5
8.1 1.3
8.0 1.2
8.0
145
125
83
12 months
18 months
24 months
3.1 0.8 149
3.1 0.8 125
3.1 0.8 84
24.7
24.8
24.5
6.3 131
6.1 95
6.8 64
N 145 Pulmonary function tests Baseline EVl (1) MLXl SD N
3.2 0.8 149
DLo (ml/min/mmHg) MWI 25.6 SD 6.7
P339
N
Nateglinide Is Effective and Safe in Elderly Patients with ‘ljpe 2 Diabetes S. MALLOWS, C. Guitard, Sharon Shen, M. Gatlin. Novanis Pharmaceuticals. NJ: Base1
(FEV,: Forced expiratory volume in 1 set; DLo:
Background and Aims: Nateglinide (NAT) is a fast acting, short duration insulinotropic agent which improves mealtime glucose control by enhanc-
PlaC&
N=239
131
1.2
Diffusion capacity)
Conclusions: HbAi, and pulmonary function tests this broad cohort of patients with type 1 or type years of INH therapy. These results suggest that and pulmonary safety of INH, shown previously in sustained long-term.
have been stable for 2 diabetes during 2 the clinical efficacy short-term trials, are