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Adjunctive therapy with inhaled insulin improves glycemic control in patients with type 2 diabetes failing oral agents
s74
Poster Session I
P341
P343
Adjunctive Therapy with Inhaled Insulin Improves Glycemic Control in Patients with ‘Qpe- 2 Diabetes Failing Oral Agents S.R. WEISS ‘, S. Berge$, S. Cheng3, I. Kourides3, W.H. Landschulz3, R.A. Gelfand3. ‘San Diego, CA, United States of America: ’ Chicago, IL, United States of America; 3 Pfizer Inc, Groton, CT United States of America
The Effect of Insulin ‘Ihzatment on Clinical and Biochemical Parameters in Elderly Asian ‘ljpe 2 Diabetes Patients: A Singapore Study C.H. LEE, S. Tavintharan, J.J. Mukherjee, V. Au. Department of Medicine, Changi General Hospital, Singapore
Aims: Patients with type 2 diabetes failing oral agent therapy often resist initiating insulin therapy, at least partially due to the need for injections. This study assessed whether the addition of a novel inhaled insulin (INH) pre-meals to usual oral agent (OA) therapy improved glycemic control in patients with type 2 diabetes failing on oral agents. Methods: Study entry required HbAI, z 8.0% despite therapeutic doses of a sulfonylurea (e.g., 5 mg/day glyburide) and/or metformin (1.5 g/day). After a l-month run-in phase, 69 subjects from 9 sites were randomized to a 3-month treatment period with either continued usual OA alone or usual OA plus INH (l-2 inhalations TID before meals). INH doses were titrated based on QID glucose testing. Results: For the 68 subjects with complete data, baseline HbAI, was comparable in the 2 groups: 9.96 f 1.26% for OA alone (n=36) and 9.90 + 1.14% for OA plus INH (n=32). While patients on OA alone showed little change in HbAt, after 12 weeks (-0.06 f 0.17%), those receiving INH plus OA exhibited a marked improvement in HbAI, (-2.28 f 0.18%, p
P342 Pharmacological Reproducibility of Pre-Meal Inhaled Insulin Is Comparable to Injected Insulin in Patients with Type 2 Diabetes R.A. GELFAND’,S.L. Schwartz*,M. Horton3,C.G.Law’,E.F.Pun’. ’ Pfizer Inc, Gmton, CR 2 San Antonio, TX: ‘Austin, TX Aims: The low therapeutic index of insulin makes reproducibility of dosing essential for optimal glycemic control without excessive hypoglycemia. Using a novel dry powder aerosol system to deliver human insulin via the lungs, we studied the pharmacokinetics and post-prandial glucose control of pre-meal inhaled insulin (INH) compared with subcutaneous regular insulin (SC) in patients with type 2 diabetes. Methods: 16 non-insulin-treated patients underwent 5 standardized (Sustacal) test-meal sessions, first with no therapy (baseline), then in a 4-way, randomized-sequence crossover involving 2 INH and 2 SC sessions. Doses were given 10 min pre-meal (INH dose: 4-6 mg of insulin as a 20% dry powder insulin formulation; SC dose: 0.2 U/kg). Results: Postprandial hyperglycemia (baseline 2-h plasma glucose increment of +I00 f 33 mg/dl) (mean f SD) was reduced to the same extent by INH (to +53 f 54 mg/dl) or SC (to +57 f 41 mg/dl), reflecting an augmented postprandial plasma insulin increment after INH (to +94 f 34 pU/ml) and SC (to +98 & 3O$J/ml) compared with baseline (+61 rt 24 @U/ml). Reproducibility, assessed by the absolute intrasubject differences between the 2 same-route dosing sessions, was indistinguishable between INH and SC for all responses measured (insulin AUC, C,,,, T,,,; glucose AUCo.sh, AUG_3h. 2-h, C,,,, C,i,, excursion (C,,,-C,i,)). INH was very well tolerated, and there were no changes in spirometry (FEV,) following treatment. Conclusion: At doses of SC and INH that reduce postprandial hyperglycemia comparably in patients with type 2 diabetes, reproducibility of inhaled insulin (even in inexperienced users) is as good as that of SC.
Although insulin is not contraindicated in elderly type 2 diabetic subjects, its use continues to invoke questions of safety and appropriateness. In Asian populations, socio-cultural questions of coping and acceptance often color the issue. We conducted a retrospective study to look at insulin treatment in Asian type 2 diabetic patients aged 65 years and older who commenced insulin therapy because of diet failure and oral agent failure. We analyzed the charts of 120 patients seen over 42 months at our hospital’s diabetes center to obtain clinical and biochemical information pre- and post-insulin treatment. In addition, the subjects completed the SF-12 Health Survey questionnaire to assess the impact of insulin therapy on physical and mental well being. Results: The mean age of the study cohort (53 males, 67 females) was 74 years (range 65-87). Fifty-five percent were Chinese, 28% Malay and 17% Indian. Baseline glycated hemoglobin (HbAI,) was 11.7 f 3.8% and baseline fasting plasma glucose 11.4 f 3.4 mM. One hundred and nine patients (90.8%) received a twice-daily regime, 6.7% were on bedtime insulin and 2.5% received more than 2 injections daily. Mean total daily dose was 43 f 16 U. The syringe method was used by 66.7% while 33.3% used a pen-injector. Forty-five percent administered insulin themselves, while 41% relied consistently on a family member to do it. The glycemic status of all patients improved after commencing insulin, with 71.1% achieving fasting plasma glucose between 4 to 10 mM (mean 9.0 f 0.4 mM) and 55.8% achieving HbAlc below 8% (mean 8.0 4 0.2%). Insulin therapy did not increase body mass index significantly or affect serum creatinine, total cholesterol or LDL cholesterol. Fasting triglycerides fell from 2.9 Z!C0.5 to 1.9 f 0.2 n&l (p=O.O3). 18.3% of subjects reported hypoglycemic episodes, and of these, only 5 episodes resulted in hospital admissions. There were no deaths in the study period. In the SF-12 assessment, we found a mean Physical Component Score (PCS) of 39 f 10, and a mean Mental Component Score (MCS) of 48 f 10. These scores may suggest that our study subjects, despite physical disability, were able to cope well with insulin injections and their disease. Our study suggests that elderly Asian type 2 diabetes patients were able to learn, adapt to, and accept insulin therapy. There were no significant adverse events associated with insulin use and no negative impact on clinical and biochemical parameters.
P344 Effect Pf Miglitol on Type 2 Diabetic Patients NIKOLAOS A. SAILER, Helias D. Stavridis, Cohn Jhonston, Felix Xavier, Gerasimos S. Spathis. Miglitol is a new d-glucosidase inhibitor. Following a two-week run-in period, 20 Type 2 diabetics, (10 males) with diabetes of at least 6 months duration (or stabilized for at least 3 months), 40-75 years, non obese, with HbA1>8% on diet (n=5) or sulphonylureas (n=l5) were blindly randomized to receive either placebo or miglitol50 mg tds, for 4 weeks with a 2 week wash-out period on placebo (double blind, placebo controlled, crossover trial). Adverse event monitoring was done at each visit. At the end of the placebo period mean fasting blood glucose = 13.4+3.4mmol/l, HbAl = 9.5f2.8%, fructosamine = 3.2f0.56 nmol/mg, total cholesterol = 6.59+1.28mmol/l, triglycerides = 1.9f1.02 mmoV1, body weight = 74.7+14 kg. At the end of the actual therapy mean fasting blood glucose = 12.8f3.2mmol/l, HbAl = 9,86f2,8%, fructosamine = 3,IztO,56nmol/mg, total cholesterol = 6,7f1,2mmol/l, triglycerides = 2,02+1,25mmol/l, body weight = 74,7fl4,4 kg. There was no statistical difference between miglitol and placebo in fasting blood glucose (p< 0.99). HbAl (p
Poster Session I
P341
P343
Adjunctive Therapy with Inhaled Insulin Improves Glycemic Control in Patients with ‘Qpe- 2 Diabetes Failing Oral Agents S.R. WEISS ‘, S. Berge$, S. Cheng3, I. Kourides3, W.H. Landschulz3, R.A. Gelfand3. ‘San Diego, CA, United States of America: ’ Chicago, IL, United States of America; 3 Pfizer Inc, Groton, CT United States of America
The Effect of Insulin ‘Ihzatment on Clinical and Biochemical Parameters in Elderly Asian ‘ljpe 2 Diabetes Patients: A Singapore Study C.H. LEE, S. Tavintharan, J.J. Mukherjee, V. Au. Department of Medicine, Changi General Hospital, Singapore
Aims: Patients with type 2 diabetes failing oral agent therapy often resist initiating insulin therapy, at least partially due to the need for injections. This study assessed whether the addition of a novel inhaled insulin (INH) pre-meals to usual oral agent (OA) therapy improved glycemic control in patients with type 2 diabetes failing on oral agents. Methods: Study entry required HbAI, z 8.0% despite therapeutic doses of a sulfonylurea (e.g., 5 mg/day glyburide) and/or metformin (1.5 g/day). After a l-month run-in phase, 69 subjects from 9 sites were randomized to a 3-month treatment period with either continued usual OA alone or usual OA plus INH (l-2 inhalations TID before meals). INH doses were titrated based on QID glucose testing. Results: For the 68 subjects with complete data, baseline HbAI, was comparable in the 2 groups: 9.96 f 1.26% for OA alone (n=36) and 9.90 + 1.14% for OA plus INH (n=32). While patients on OA alone showed little change in HbAt, after 12 weeks (-0.06 f 0.17%), those receiving INH plus OA exhibited a marked improvement in HbAI, (-2.28 f 0.18%, p
P342 Pharmacological Reproducibility of Pre-Meal Inhaled Insulin Is Comparable to Injected Insulin in Patients with Type 2 Diabetes R.A. GELFAND’,S.L. Schwartz*,M. Horton3,C.G.Law’,E.F.Pun’. ’ Pfizer Inc, Gmton, CR 2 San Antonio, TX: ‘Austin, TX Aims: The low therapeutic index of insulin makes reproducibility of dosing essential for optimal glycemic control without excessive hypoglycemia. Using a novel dry powder aerosol system to deliver human insulin via the lungs, we studied the pharmacokinetics and post-prandial glucose control of pre-meal inhaled insulin (INH) compared with subcutaneous regular insulin (SC) in patients with type 2 diabetes. Methods: 16 non-insulin-treated patients underwent 5 standardized (Sustacal) test-meal sessions, first with no therapy (baseline), then in a 4-way, randomized-sequence crossover involving 2 INH and 2 SC sessions. Doses were given 10 min pre-meal (INH dose: 4-6 mg of insulin as a 20% dry powder insulin formulation; SC dose: 0.2 U/kg). Results: Postprandial hyperglycemia (baseline 2-h plasma glucose increment of +I00 f 33 mg/dl) (mean f SD) was reduced to the same extent by INH (to +53 f 54 mg/dl) or SC (to +57 f 41 mg/dl), reflecting an augmented postprandial plasma insulin increment after INH (to +94 f 34 pU/ml) and SC (to +98 & 3O$J/ml) compared with baseline (+61 rt 24 @U/ml). Reproducibility, assessed by the absolute intrasubject differences between the 2 same-route dosing sessions, was indistinguishable between INH and SC for all responses measured (insulin AUC, C,,,, T,,,; glucose AUCo.sh, AUG_3h. 2-h, C,,,, C,i,, excursion (C,,,-C,i,)). INH was very well tolerated, and there were no changes in spirometry (FEV,) following treatment. Conclusion: At doses of SC and INH that reduce postprandial hyperglycemia comparably in patients with type 2 diabetes, reproducibility of inhaled insulin (even in inexperienced users) is as good as that of SC.
Although insulin is not contraindicated in elderly type 2 diabetic subjects, its use continues to invoke questions of safety and appropriateness. In Asian populations, socio-cultural questions of coping and acceptance often color the issue. We conducted a retrospective study to look at insulin treatment in Asian type 2 diabetic patients aged 65 years and older who commenced insulin therapy because of diet failure and oral agent failure. We analyzed the charts of 120 patients seen over 42 months at our hospital’s diabetes center to obtain clinical and biochemical information pre- and post-insulin treatment. In addition, the subjects completed the SF-12 Health Survey questionnaire to assess the impact of insulin therapy on physical and mental well being. Results: The mean age of the study cohort (53 males, 67 females) was 74 years (range 65-87). Fifty-five percent were Chinese, 28% Malay and 17% Indian. Baseline glycated hemoglobin (HbAI,) was 11.7 f 3.8% and baseline fasting plasma glucose 11.4 f 3.4 mM. One hundred and nine patients (90.8%) received a twice-daily regime, 6.7% were on bedtime insulin and 2.5% received more than 2 injections daily. Mean total daily dose was 43 f 16 U. The syringe method was used by 66.7% while 33.3% used a pen-injector. Forty-five percent administered insulin themselves, while 41% relied consistently on a family member to do it. The glycemic status of all patients improved after commencing insulin, with 71.1% achieving fasting plasma glucose between 4 to 10 mM (mean 9.0 f 0.4 mM) and 55.8% achieving HbAlc below 8% (mean 8.0 4 0.2%). Insulin therapy did not increase body mass index significantly or affect serum creatinine, total cholesterol or LDL cholesterol. Fasting triglycerides fell from 2.9 Z!C0.5 to 1.9 f 0.2 n&l (p=O.O3). 18.3% of subjects reported hypoglycemic episodes, and of these, only 5 episodes resulted in hospital admissions. There were no deaths in the study period. In the SF-12 assessment, we found a mean Physical Component Score (PCS) of 39 f 10, and a mean Mental Component Score (MCS) of 48 f 10. These scores may suggest that our study subjects, despite physical disability, were able to cope well with insulin injections and their disease. Our study suggests that elderly Asian type 2 diabetes patients were able to learn, adapt to, and accept insulin therapy. There were no significant adverse events associated with insulin use and no negative impact on clinical and biochemical parameters.
P344 Effect Pf Miglitol on Type 2 Diabetic Patients NIKOLAOS A. SAILER, Helias D. Stavridis, Cohn Jhonston, Felix Xavier, Gerasimos S. Spathis. Miglitol is a new d-glucosidase inhibitor. Following a two-week run-in period, 20 Type 2 diabetics, (10 males) with diabetes of at least 6 months duration (or stabilized for at least 3 months), 40-75 years, non obese, with HbA1>8% on diet (n=5) or sulphonylureas (n=l5) were blindly randomized to receive either placebo or miglitol50 mg tds, for 4 weeks with a 2 week wash-out period on placebo (double blind, placebo controlled, crossover trial). Adverse event monitoring was done at each visit. At the end of the placebo period mean fasting blood glucose = 13.4+3.4mmol/l, HbAl = 9.5f2.8%, fructosamine = 3.2f0.56 nmol/mg, total cholesterol = 6.59+1.28mmol/l, triglycerides = 1.9f1.02 mmoV1, body weight = 74.7+14 kg. At the end of the actual therapy mean fasting blood glucose = 12.8f3.2mmol/l, HbAl = 9,86f2,8%, fructosamine = 3,IztO,56nmol/mg, total cholesterol = 6,7f1,2mmol/l, triglycerides = 2,02+1,25mmol/l, body weight = 74,7fl4,4 kg. There was no statistical difference between miglitol and placebo in fasting blood glucose (p< 0.99). HbAl (p