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Orville G Kolterman - One of the best experts on this subject based on the ideXlab platform.
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doubleblind, placebo-controlled trial of flexible-dose fesoterodine in subjects with overactive bladder. Urology
2016Co-Authors: Steve Edelman, Susan Strobel, Karen Lutz, Yan Wang, Bei Zhang, Satish Garg, Juan Frias, David Maggs, Orville G KoltermanAbstract:OBJECTIVE — To assess safety, efficacy, and tolerability of Pramlintide dose escalation with proactive mealtime insulin reduction, followed by insulin optimization, in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS — This 29-week, double-blind, placebo-controlled study randomized 296 patients to Pramlintide or placebo as an adjunct to insulin. During initiation, Pramlintide was escalated from 15 to 60 g/meal (15-g increments) with recommended reductions (30–50%) in mealtime insulin. Insulin was subsequently adjusted to optimize glycemic control. End points included safety and change in HbA1c (A1C), postprandial glucose, insulin, weight, and tolerability. RESULTS — Baseline A1C was 8.1 % for both groups and at week 29 had decreased compa-rably (Pramlintide 0.5 % [95 % CI 0.61 to 0.33]; placebo 0.5 % [0.63 to 0.35]). Pramlintide treatment significantly reduced postprandial glucose excursions (incremental area under the curve [AUC]0–3h: Pramlintide 175 40, placebo 64 38 mg h 1 dl1; P 0.0005) and weight (Pramlintide1.3 0.30, placebo1.2 0.30 kg; P 0.0001). At wee
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fixed ratio dosing of Pramlintide with regular insulin before a standard meal in patients with type 1 diabetes
Diabetes Obesity and Metabolism, 2015Co-Authors: Matthew C Riddle, Peter Ohman, K C J Yuen, T W A De Bruin, K Herrmann, John Xu, Orville G KoltermanAbstract:Amylin is co‐secreted with insulin and is therefore lacking in patients with type 1 diabetes. Replacement with fixed ratio co‐administration of insulin and the amylin analogue Pramlintide may be superior to separate dosing. This concept was evaluated in a ratio‐finding study. Patients with type 1 diabetes were enrolled in a randomized, single‐masked, standard breakfast crossover study using regular human insulin injected simultaneously with Pramlintide 6, 9 or 12 mcg/unit insulin or placebo. Insulin dosage was reduced by 30% from patients' usual estimates. Plasma glucose, glucagon and Pramlintide and adverse events were assessed. All ratios reduced 0–3‐h glucose and glucagon increments by >50%. No hypoglycaemia occurred. Adverse events were infrequent and generally mild. All Pramlintide/insulin ratios markedly and safely reduced glycaemic excursions and suppressed glucagon secretion in the immediate postprandial state. Further study using one of these ratios to explore the efficacy and safety of longer‐term meal‐time and basal hormone replacement is warranted.
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Pramlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Patients With Type 2 Diabetes
2015Co-Authors: Priscilla A. Hollander, Christian Weyer, David G Maggs, Larry Z Shen, Philip Levy, Mark S. Fineman, Susan A. Strobel, Orville G KoltermanAbstract:OBJECTIVE — Mealtime amylin replacement with the human amylin analog Pramlintide, as an adjunct to mealtime insulin replacement, reduces postprandial glucose excursions in patients with type 2 diabetes. The aim of the present study was to assess the long-term efficacy and safety of Pramlintide in this patient population. RESEARCH DESIGN AND METHODS — In a 52-week, double-blind, placebo-controlled, parallel-group, multicenter study, 656 patients with type 2 diabetes (age 57 1
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Pramlintide improved measures of glycemic control and body weight in patients with type 1 diabetes mellitus undergoing continuous subcutaneous insulin infusion therapy
Postgraduate Medicine, 2013Co-Authors: Kathrin Herrmann, Karen Lutz, David G Maggs, Kevin Shan, Juan P Frias, Steven V Edelman, Steven Chen, Orville G KoltermanAbstract:AbstractObjective: To assess the safety and efficacy of the addition of Pramlintide to continuous subcutaneous insulin infusion (CSII) therapy in patients with type 1 diabetes mellitus (T1DM). Research Design and Methods: We conducted a post hoc analysis of 2 studies: a 29-week, multicenter, randomized, double-blind, placebo-controlled trial (referred to as RCT) (Pramlintide, n = 82; placebo, n = 73) and an open-ended, multicenter, open-label, single-arm, observational study (referred to as clinical practice trial) (n =150), which assessed the addition of Pramlintide to CSII therapy in patients with T1DM. Pramlintide was initiated at 15 μg and titrated to 30 or 60 μg with major meals. The mealtime insulin dose was reduced by 30% to 50% at initiation, and then adjusted to optimize glycemic control. Endpoints at 29 weeks (RCT) and 6 months (clinical practice trial) included change in glycated hemoglobin (HbA1c) level, insulin dose, body weight, pre- and postprandial blood glucose level, and tolerability and...
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In silico design of optimal ratio for co-administration of Pramlintide and insulin in type 1 diabetes.
Diabetes Technology & Therapeutics, 2013Co-Authors: Francesco Micheletto, Orville G Kolterman, Kathrin Herrmann, Chiara Dalla Man, Elaine Chiquette, Jörg Schirra, Boris P. Kovatchev, Claudio CobelliAbstract:Abstract Background: The ability to simulate in silico experiments is crucial for fast and cost-effective preliminary studies prior to clinical trials. We present an in silico approach to the design of optimal Pramlintide-to-insulin (P/I) ratios, using our computer simulator of the human metabolic system, with a population of virtual adult type 1 diabetes mellitus patients and with individual parameters modified to account for the dynamic effects of Pramlintide. Materials and Methods: A model of Pramlintide action on gastric emptying was built using data of 15 type 1 diabetes mellitus subjects studied twice with a standardized dual-tracer meal on placebo and Pramlintide, which was incorporated in our type 1 diabetes simulator. Extensive in silico experiments on 100 virtual subjects were performed to optimize the co-administration of Pramlintide and insulin prior to its submission to clinical trials; several P/I ratios were tested in terms of efficacy, in attenuating postprandial hyperglycemia, and in hypo...
Christian Weyer - One of the best experts on this subject based on the ideXlab platform.
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Pramlintide Treatment Reduces 24-Hour Caloric Intake and Meal Sizes, and Improves Control of Eating in Obese Subjects: A 6-Week Translational Research Study Running Head: Effect of amylin agonism on human eating behavior
2016Co-Authors: Steven R Smith, Colleen Burns, Cameron W Lush, Brock E Schroeder, Nicole C Kesty, Kim Chen, John E. Blundell, Cinzia Ellero, Amy E. Halseth, Christian WeyerAbstract:Evidence from rodent studies indicates that the -cell-derived neurohormone amylin exerts multiple effects on eating behavior, including reductions in meal size, intake of highly-palatable foods, and stress-induced sucrose consumption. To assess the effect of amylin agonism on human eating behavior, we conducted a randomized, blinded, placebo-controlled, multicenter study investigating the effects of the amylin analog Pramlintide on body weight, 24-hour caloric intake, portion sizes, “fast-food ” intake, and perceived control of eating in 88 obese subjects. After a 2-day placebo lead-in, subjects self-administered Pramlintide (180 Cg) or placebo by subcutaneous injection 15 minutes before meals for 6 weeks, without concomitant lifestyle modifications. Compared to placebo, Pramlintide treatment elicited significant mean reductions from baseline in body weight on Day 44 (-2.1 ± 0.3 % vs
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Pramlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Patients With Type 2 Diabetes
2015Co-Authors: Priscilla A. Hollander, Christian Weyer, David G Maggs, Larry Z Shen, Philip Levy, Mark S. Fineman, Susan A. Strobel, Orville G KoltermanAbstract:OBJECTIVE — Mealtime amylin replacement with the human amylin analog Pramlintide, as an adjunct to mealtime insulin replacement, reduces postprandial glucose excursions in patients with type 2 diabetes. The aim of the present study was to assess the long-term efficacy and safety of Pramlintide in this patient population. RESEARCH DESIGN AND METHODS — In a 52-week, double-blind, placebo-controlled, parallel-group, multicenter study, 656 patients with type 2 diabetes (age 57 1
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enhanced weight loss with Pramlintide metreleptin an integrated neurohormonal approach to obesity pharmacotherapy
Obesity, 2009Co-Authors: Eric Ravussin, Joy E Koda, Holly Maier, Steven R Smith, Julie A Mitchell, Reshma Shringarpure, Kevin Shan, Christian WeyerAbstract:The neurohormonal control of body weight involves a complex interplay between long-term adiposity signals (e.g., leptin), and short-term satiation signals (e.g., amylin). In diet-induced obese (DIO) rodents, amylin/leptin combination treatment led to marked, synergistic, fat-specific weight loss. To evaluate the weight-lowering effect of combined amylin/leptin agonism (with Pramlintide/metreleptin) in human obesity, a 24-week, randomized, double-blind, active-drug-controlled, proof-of-concept study was conducted in obese or overweight subjects (N = 177; 63% female; 39 +/- 8 years; BMI 32.0 +/- 2.1 kg/m(2); 93.3 +/- 13.2 kg; mean +/- s.d.). After a 4-week lead-in period with Pramlintide (180 microg b.i.d. for 2 weeks, 360 microg b.i.d. thereafter) and diet (40% calorie deficit), subjects achieving 2-8% weight loss were randomized 1:2:2 to 20 weeks of treatment with metreleptin (5 mg b.i.d.), Pramlintide (360 microg b.i.d.), or Pramlintide/metreleptin (360 microg/5 mg b.i.d.). Combination treatment with Pramlintide/metreleptin led to significantly greater weight loss from enrollment to week 20 (-12.7 +/- 0.9%; least squares mean +/- s.e.) than treatment with Pramlintide (-8.4 +/- 0.9%; P < 0.001) or metreleptin (-8.2 +/- 1.3%; P < 0.01) alone (evaluable, N = 93). The greater reduction in body weight was significant as early as week 4, and weight loss continued throughout the study, without evidence of a plateau. The most common adverse events with Pramlintide/metreleptin were injection site events and nausea, which were mostly mild to moderate and decreased over time. These results support further development of Pramlintide/metreleptin as a novel, integrated neurohormonal approach to obesity pharmacotherapy.
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sustained weight loss following 12 month Pramlintide treatment as an adjunct to lifestyle intervention in obesity
Diabetes Care, 2008Co-Authors: Steve Smith, Louis J Aronne, Amy Halseth, Colleen Burns, Nicole C Kesty, Christian WeyerAbstract:OBJECTIVE —To assess long-term weight loss efficacy and safety of Pramlintide used at different dosing regimens and in conjunction with lifestyle intervention (LSI). RESEARCH DESIGN AND METHODS —In a 4-month, double-blind, placebo-controlled, dose-ranging study, 411 obese subjects were randomized to receive Pramlintide (six arms: 120, 240, and 360 μg b.i.d. and t.i.d.) or placebo in conjunction with a structured LSI program geared toward weight loss. Of the 4-month evaluable subjects ( n = 270), 77% opted to continue preexisting treatment during an 8-month single-blind extension (LSI geared toward weight maintenance). RESULTS —At month 4, mean weight loss from baseline in the Pramlintide arms ranged from 3.8 ± 0.7 to 6.1 ± 0.8 kg (2.8 ± 0.8 kg with placebo). By month 12, initial 4-month weight loss was regained in the placebo group but was maintained in all but the 120-μg b.i.d. group. Placebo-corrected weight loss with 120 μg t.i.d. and 360 μg b.i.d. averaged 3.2 ± 1.2 kg (3.1 ± 1.1% body wt) and 3.3 ± 1.1 kg (3.1 ± 1.0% body wt), respectively, at month 4 (both P n = 270) and 6.1 ± 2.1 kg (5.6 ± 2.1% body wt) and 7.2 ± 2.3 kg (6.8 ± 2.3% body wt), respectively, at month 12 (both P n = 146). At month 12, 40 and 43% of subjects treated with 120 μg t.i.d. and 360 μg b.i.d., respectively, achieved ≥10% weight loss (vs. 12% for placebo). Nausea, the most common adverse event with Pramlintide in the 4-month study (9–29% Pramlintide vs. 2% placebo), was generally mild to moderate and occurred in CONCLUSIONS —When used over 12 months as an adjunct to LSI, Pramlintide treatment, with low-dose three-times-daily or higher-dose two-times-daily regimens, helped obese subjects achieve greater initial weight loss and enhanced long-term maintenance of weight loss.
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progressive reduction in body weight after treatment with the amylin analog Pramlintide in obese subjects a phase 2 randomized placebo controlled dose escalation study
The Journal of Clinical Endocrinology and Metabolism, 2007Co-Authors: Louis J Aronne, Amy Halseth, Colleen Burns, Cameron W Lush, Nicole C Kesty, Ken Fujioka, Vanita R Aroda, Kim Chen, Christian WeyerAbstract:Context: In previous 1-yr trials, treatment with Pramlintide (120 μg), an analog of the β-cell hormone amylin, induced sustained reductions in A1C and body weight in insulin-using subjects with type 2 diabetes. Objective: To assess the potential of Pramlintide as an antiobesity agent, we assessed the weight effect, safety, and tolerability of Pramlintide in non-insulin-treated obese subjects with and without type 2 diabetes at doses greater than previously studied. Design/Setting: We performed a randomized, double-blind, placebo-controlled, multicenter study. Patients: A total of 204 obese subjects [80/20% female/male, age 48 ± 10 yr, and body mass index 37.8 ± 5.6 kg/m2 (mean ± sd)] participated in the study. Intervention: For 16 wk, without concomitant lifestyle intervention, subjects self-administered Pramlintide (nonforced dose escalation ≤ 240 μg) or placebo via sc injection three times a day before meals. Main Outcome Measures: Weight, waist circumference, tolerability, and safety were the main outc...
David G Maggs - One of the best experts on this subject based on the ideXlab platform.
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Impact of Disease Duration on the Effects of Pramlintide in Type 1 Diabetes: A Post Hoc Analysis of Three Clinical Trials.
Advances in therapy, 2016Co-Authors: Kathrin Herrmann, Steven C. Brunell, Ming Zhou, David G MaggsAbstract:Introduction Adjunctive mealtime use of the amylin analog Pramlintide improves postprandial hyperglycemia in patients with type 1 diabetes. This post hoc analysis of three randomized trials evaluated whether disease duration affected responses to Pramlintide.
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Pramlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Patients With Type 2 Diabetes
2015Co-Authors: Priscilla A. Hollander, Christian Weyer, David G Maggs, Larry Z Shen, Philip Levy, Mark S. Fineman, Susan A. Strobel, Orville G KoltermanAbstract:OBJECTIVE — Mealtime amylin replacement with the human amylin analog Pramlintide, as an adjunct to mealtime insulin replacement, reduces postprandial glucose excursions in patients with type 2 diabetes. The aim of the present study was to assess the long-term efficacy and safety of Pramlintide in this patient population. RESEARCH DESIGN AND METHODS — In a 52-week, double-blind, placebo-controlled, parallel-group, multicenter study, 656 patients with type 2 diabetes (age 57 1
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Pramlintide improved measures of glycemic control and body weight in patients with type 1 diabetes mellitus undergoing continuous subcutaneous insulin infusion therapy
Postgraduate Medicine, 2013Co-Authors: Kathrin Herrmann, Karen Lutz, David G Maggs, Kevin Shan, Juan P Frias, Steven V Edelman, Steven Chen, Orville G KoltermanAbstract:AbstractObjective: To assess the safety and efficacy of the addition of Pramlintide to continuous subcutaneous insulin infusion (CSII) therapy in patients with type 1 diabetes mellitus (T1DM). Research Design and Methods: We conducted a post hoc analysis of 2 studies: a 29-week, multicenter, randomized, double-blind, placebo-controlled trial (referred to as RCT) (Pramlintide, n = 82; placebo, n = 73) and an open-ended, multicenter, open-label, single-arm, observational study (referred to as clinical practice trial) (n =150), which assessed the addition of Pramlintide to CSII therapy in patients with T1DM. Pramlintide was initiated at 15 μg and titrated to 30 or 60 μg with major meals. The mealtime insulin dose was reduced by 30% to 50% at initiation, and then adjusted to optimize glycemic control. Endpoints at 29 weeks (RCT) and 6 months (clinical practice trial) included change in glycated hemoglobin (HbA1c) level, insulin dose, body weight, pre- and postprandial blood glucose level, and tolerability and...
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a double blind placebo controlled trial assessing Pramlintide treatment in the setting of intensive insulin therapy in type 1 diabetes
Diabetes Care, 2006Co-Authors: Steve V Edelman, Susan Strobel, Karen Lutz, David G Maggs, Yan Wang, Satish K Garg, Juan P Frias, Bei Zhang, Orville G KoltermanAbstract:OBJECTIVE —To assess safety, efficacy, and tolerability of Pramlintide dose escalation with proactive mealtime insulin reduction, followed by insulin optimization, in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS —This 29-week, double-blind, placebo-controlled study randomized 296 patients to Pramlintide or placebo as an adjunct to insulin. During initiation, Pramlintide was escalated from 15 to 60 μg/meal (15-μg increments) with recommended reductions (30–50%) in mealtime insulin. Insulin was subsequently adjusted to optimize glycemic control. End points included safety and change in HbA1c (A1C), postprandial glucose, insulin, weight, and tolerability. RESULTS —Baseline A1C was 8.1% for both groups and at week 29 had decreased comparably (Pramlintide −0.5% [95% CI −0.61 to −0.33]; placebo −0.5% [−0.63 to −0.35]). Pramlintide treatment significantly reduced postprandial glucose excursions (incremental area under the curve [AUC]0–3h: Pramlintide −175 ± 40, placebo −64 ± 38 mg · h−1 · dl−1; P < 0.0005) and weight (Pramlintide −1.3 ± 0.30, placebo +1.2 ± 0.30 kg; P < 0.0001). At week 29, insulin dose decreased by 28 and 4% in Pramlintide- and placebo-treated groups, respectively. Nausea, reported by 63 and 36% of patients in Pramlintide and placebo groups ( P < 0.01), respectively, was predominately mild to moderate in intensity. Severe hypoglycemia rates were low in both groups (Pramlintide 0.57 ± 0.09, placebo 0.30 ± 0.06 event rate/patient-year; P < 0.05), with increased rates observed in patients remaining at 30 μg Pramlintide. CONCLUSIONS —Pramlintide dose escalation with reduced mealtime insulin was effective during therapy initiation in patients with type 1 diabetes. While both groups experienced equivalent A1C reductions relative to placebo, Pramlintide-treated patients experienced reductions in postprandial glucose excursions and weight, not achievable with insulin therapy alone.
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the effect of Pramlintide on hormonal metabolic or symptomatic responses to insulin induced hypoglycaemia in patients with type 1 diabetes
Diabetes Obesity and Metabolism, 2005Co-Authors: Stephanie A Amiel, Christian Weyer, James A Ruggles, Orville G Kolterman, Sherwyn Schwartz, Simon Heller, I A Macdonald, L Klaff, David G MaggsAbstract:Background: Pramlintide, a human amylin analogue, is a potential new adjunctive therapy to insulin for patients with type 1 diabetes and insulin-using patients with type 2 diabetes. Early clinical trials have shown a transient increased risk of hypoglycaemia in some patients at the time of initiating Pramlintide therapy. This may be the result of combining the postprandial glucose, lowering effect of Pramlintide with the existing hypoglycaemic potential of insulin without appropriate adjustment of insulin doses. However, the possibility that Pramlintide may exert an independent detrimental effect on the physiological responses to insulin-induced hypoglycaemia needs to be excluded. Methods: We conducted three separate randomized, placebo-controlled studies in patients with type 1 diabetes treated with adjunctive Pramlintide. These studies utilized Pramlintide at high doses (either 0.1–1 mg Pramlintide daily or 0.1–0.8 mg Pramlintide four times a day for 5 or 6 days) as well as doses closer to those anticipated for therapeutic usage (30, 100 or 300 µg three times daily for 14 days), and examined the hormonal, metabolic and symptomatic responses to an insulin-infusion hypoglycaemic challenge conducted at baseline and after days of therapy. Results and conclusion: Pramlintide had no effect on the counter-regulatory hormonal, metabolic and symptomatic responses to hypoglycaemia. These findings demonstrated that Pramlintide, when used as adjunctive therapy to insulin in patients with type 1 diabetes, has no independent effect on the response to hypoglycaemia.
Mark Fineman - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetics of an oral drug acetaminophen administered at various times relative to subcutaneous injection of Pramlintide in subjects with type 2 diabetes
The Journal of Clinical Pharmacology, 2007Co-Authors: Terrie Kellmeyer, Juan P Frias, Yan Wang, Nicole C Kesty, Mark FinemanAbstract:Pramlintide, an adjunct treatment to mealtime insulin for patients with type 2 and type 1 diabetes, aids glycemic control by suppressing postprandial glucagon secretion, slowing gastric emptying, and enhancing satiety. Because gastric emptying affects oral medication absorption, this placebo-controlled, single-blind, crossover study examined the absorption of 1000 mg of acetaminophen elixir administered -2, -1, 0, +1, and +2 hours relative to Pramlintide (120 microg) or 0 hours relative to placebo in 24 patients with type 2 diabetes. When acetaminophen administration occurred 0, +1, or +2 hours relative to Pramlintide, the maximum observed plasma concentration of acetaminophen decreased 14% to 29%, and time to maximum observed plasma concentration increased by 0.8 to 1.2 hours compared with administration 0 hours relative to placebo. Pramlintide treatment slowed but did not alter the extent of acetaminophen absorption (area under the concentration-time curve). No serious adverse events or withdrawals were reported. Oral agents should be administered at least 1 hour before or 2 hours after Pramlintide injection if rapid onset of action is required for efficacy.
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properties of Pramlintide and insulin upon mixing
American Journal of Health-system Pharmacy, 2005Co-Authors: Christian Weyer, Mark Fineman, Susan Strobel, Orville G Kolterman, Larry Z Shen, Joann Data, Mario F SylvestriAbstract:Purpose. The pharmacokinetics, pharmacodynamics, and safety of Pramlintide and various insulin formulations in patients with type 1 diabetes mellitus (DM) when given as separate injections or mixed in the same syringe before injection were studied. Methods. In two randomized, open-label, placebo-controlled, five-period-crossover studies, patients with type 1 DM received preprandial injections of Pramlintide, short-acting insulin, and long-acting insulin administered either by separate injections or after mixing in various combinations. Serum free insulin and plasma glucose concentrations were measured for 10 hours and plasma Pramlintide concentrations for 5 hours after injection. Results. Blood samples were collected from a total of 51 patients. All treatments involving mixtures were comparable to separate injections with respect to the area under the concentration-versus-time curve (AUC) and the maximum concentration ( C max) of serum free insulin. There were some minor differences in the AUC and C max of Pramlintide. No injection-site reactions or other unexpected adverse events were observed. Conclusion. Mixing Pramlintide with short- or long-acting insulin in the same syringe before subcutaneous injection did not affect the pharmacodynamics of glucose or the pharmacokinetics of insulin or Pramlintide in a clinically significant manner.
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adjunctive therapy with Pramlintide lowers hba1c without concomitant weight gain and increased risk of severe hypoglycemia in patients with type 1 diabetes approaching glycemic targets
Experimental and Clinical Endocrinology & Diabetes, 2005Co-Authors: Robert E Ratner, Mark Fineman, Susan Strobel, Orville G Kolterman, David G Maggs, Larry Z Shen, Fred W Whitehouse, Christian WeyerAbstract:AIMS In long-term clinical trials in patients with type 1 diabetes spanning a wide range of HbA1c, addition of Pramlintide to existing insulin regimens led to reductions in HbA1c that were accompanied by weight loss and no increase in overall severe hypoglycemia event rates. Given that weight gain and increased hypoglycemia risk contribute to the difficulty of attaining HbA1c targets (<7 %), the question arose whether Pramlintide could benefit patients approaching, but not reaching glycemic targets with insulin alone. To address this question, we conducted a pooled analysis from 3 long-term clinical trials, including all patients with an entry HbA1c between 7.0 % and 8.5 %. METHODS Within the subset of patients with an entry HbA1c between 7.0 % and 8.5 % (approximately 28 % of all patients enrolled in the 3 studies), 196 were treated with placebo + insulin (baseline HbA1c 7.9+/-0.4 %, body weight 76.0+/-14.3 kg [mean+/-SD]) and 281 with Pramlintide+insulin (baseline HbA1c 7.9+/-0.4 %, body weight 75.4+/-13.1 kg). Endpoints included placebo-corrected changes from baseline to week 26 in HbA1c, body weight, and the event rate of severe hypoglycemia. RESULTS Adjunctive therapy with Pramlintide resulted in significant reductions in HbA1c and body weight from baseline to week 26 (0.3 % and 1.8 kg, placebo-corrected treatment differences, respectively, both p
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amylin replacement with Pramlintide as an adjunct to insulin therapy improves long term glycaemic and weight control in type 1 diabetes mellitus a 1 year randomized controlled trial
Diabetic Medicine, 2004Co-Authors: Robert E Ratner, Mark Fineman, Susan Strobel, Christian Weyer, David G Maggs, Larry Z Shen, R Dickey, Orville G KoltermanAbstract:AIMS The autoimmune-mediated destruction of pancreatic beta-cells in Type 1 diabetes mellitus renders patients deficient in two glucoregulatory peptide hormones, insulin and amylin. With insulin replacement alone, most patients do not achieve glycaemic goals. We aimed to determine the long-term efficacy and safety of adjunctive therapy with Pramlintide, a synthetic human amylin analogue, in patients with Type 1 diabetes. METHODS In a double-blind, placebo-controlled, parallel-group, multicentre study, 651 patients with Type 1 diabetes (age 41 +/- 13 years, HbA(1c) 8.9 +/- 1.0%, mean +/- sd) were randomized to mealtime injections of placebo or varying doses of Pramlintide, in addition to their insulin therapy, for 52 weeks. RESULTS Addition of Pramlintide [60 microg three times daily (TID) or four times daily (QID)] to insulin led to significant reductions in HbA(1c) from baseline to Week 52 of 0.29% (P < 0.011) and 0.34% (P < 0.001), respectively, compared with a 0.04% reduction in placebo group. Three times the proportion of Pramlintide- than placebo-treated patients achieved an HbA(1c) of < 7%. The greater reduction in HbA(1c) with Pramlintide was achieved without an increase in concomitant insulin use and was accompanied by a significant reduction in body weight from baseline to Week 52 of 0.4 kg in the 60 microg TID (P < 0.027) or QID (P < 0.040) Pramlintide treatment groups, compared with a 0.8-kg gain in body weight in the placebo group. The most common adverse event in Pramlintide-treated patients was transient, mild-to-moderate nausea. CONCLUSIONS These results show that mealtime amylin replacement with Pramlintide, as an adjunct to insulin therapy, improves long-term glycaemic and weight control in patients with Type 1 diabetes.
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Pramlintide reduces postprandial glucose excursions when added to insulin lispro in subjects with type 2 diabetes a dose timing study
Diabetes-metabolism Research and Reviews, 2004Co-Authors: David G Maggs, Mark Fineman, James A Ruggles, Orville G Kolterman, Sherwyn Schwartz, Yan Wang, Jonathan Kornstein, Terrie Burrell, Christian WeyerAbstract:Background To assess the postprandial glucose-lowering effect of the human amylin analog Pramlintide when given with insulin lispro in subjects with type 2 diabetes, with an emphasis on the optimal dose timing relative to meals. Methods In this randomized, single-blind, placebo-controlled, five-way crossover study, 19 subjects with type 2 diabetes using insulin lispro underwent five consecutive mixed-meal tests. In randomized order, subjects received subcutaneous injections of placebo at −15 min or 120-µg Pramlintide at −15, 0, +15, or +30 min relative to the standardized breakfast after an overnight fast. Insulin lispro was injected at 0 min at doses that were adjusted appropriately for both the content of the standardized meal and the anticipated effects of Pramlintide. Plasma glucose concentrations were measured before and during the 4-h postmeal period. Results When injected at 0 min, Pramlintide reduced the postprandial glucose excursion by 81% compared to insulin lispro + placebo (incremental AUC0–4 h (mean ± SE) 2.0 ± 1.5 vs. 10.4 ± 2.2 mmol/h/L, P < 0.05). When Pramlintide was injected at −15, +15, and +30 min, the postprandial incremental glucose AUC0–4 h was also significantly reduced (P < 0.05), but to a lesser extent (42 to 73%). Pramlintide treatment was well tolerated and no serious adverse events were reported. Conclusions Administration of Pramlintide either at or just prior to a meal caused a greater reduction in postprandial glucose than either administration of placebo or postmeal Pramlintide injections in subjects with type 2 diabetes treated with a rapid-acting insulin analog, insulin lispro. Copyright © 2004 John Wiley & Sons, Ltd.
Larry Z Shen - One of the best experts on this subject based on the ideXlab platform.
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Pramlintide as an Adjunct to Insulin Therapy Improves Long-Term Glycemic and Weight Control in Patients With Type 2 Diabetes
2015Co-Authors: Priscilla A. Hollander, Christian Weyer, David G Maggs, Larry Z Shen, Philip Levy, Mark S. Fineman, Susan A. Strobel, Orville G KoltermanAbstract:OBJECTIVE — Mealtime amylin replacement with the human amylin analog Pramlintide, as an adjunct to mealtime insulin replacement, reduces postprandial glucose excursions in patients with type 2 diabetes. The aim of the present study was to assess the long-term efficacy and safety of Pramlintide in this patient population. RESEARCH DESIGN AND METHODS — In a 52-week, double-blind, placebo-controlled, parallel-group, multicenter study, 656 patients with type 2 diabetes (age 57 1
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enhanced weight loss following coadministration of Pramlintide with sibutramine or phentermine in a multicenter trial
Obesity, 2010Co-Authors: Louis J Aronne, Amy Halseth, Colleen Burns, Stephan Miller, Larry Z ShenAbstract:Preclinical evidence suggests that pharmacotherapy for obesity using combinations of agents targeted at distinct regulatory pathways may produce robust additive or synergistic effects on weight loss. This randomized placebo-controlled trial examined the safety and efficacy of the amylin analogue Pramlintide alone or in combination with either phentermine or sibutramine. All patients also received lifestyle intervention. Following a 1-week placebo lead-in, 244 obese or overweight, nondiabetic subjects (88% female; 41 +/- 11 years; BMI 37.7 +/- 5.4 kg/m(2); weight 103 +/- 19 kg; mean +/- s.d.) received placebo subcutaneously (sc) t.i.d., Pramlintide sc (120 microg t.i.d.), Pramlintide sc (120 microg t.i.d.) + oral sibutramine (10 mg q.a.m.), or Pramlintide sc (120 microg t.i.d.) + oral phentermine (37.5 mg q.a.m.) for 24 weeks. Treatment was single-blind for subjects receiving subcutaneous medication only and open-label for subjects in the combination arms. Weight loss achieved at week 24 with either combination treatment was greater than with Pramlintide alone or placebo (P < 0.001; 11.1 +/- 1.1% with Pramlintide + sibutramine, 11.3 +/- 0.9% with Pramlintide + phentermine, -3.7 +/- 0.7% with Pramlintide; -2.2 +/- 0.7% with placebo; mean +/- s.e.). Elevations from baseline in heart rate and diastolic blood pressure were demonstrated with both Pramlintide + sibutramine (3.1 +/- 1.2 beats/min, P < 0.05; 2.7 +/- 0.9 mm Hg, P < 0.01) and Pramlintide + phentermine (4.5 +/- 1.3 beats/min, P < 0.01; 3.5 +/- 1.2 mm Hg, P < 0.001) using 24-h ambulatory monitoring. However, the majority of subjects receiving these treatments remained within normal blood pressure ranges. These results support the potential of Pramlintide-containing combination treatments for obesity.
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properties of Pramlintide and insulin upon mixing
American Journal of Health-system Pharmacy, 2005Co-Authors: Christian Weyer, Mark Fineman, Susan Strobel, Orville G Kolterman, Larry Z Shen, Joann Data, Mario F SylvestriAbstract:Purpose. The pharmacokinetics, pharmacodynamics, and safety of Pramlintide and various insulin formulations in patients with type 1 diabetes mellitus (DM) when given as separate injections or mixed in the same syringe before injection were studied. Methods. In two randomized, open-label, placebo-controlled, five-period-crossover studies, patients with type 1 DM received preprandial injections of Pramlintide, short-acting insulin, and long-acting insulin administered either by separate injections or after mixing in various combinations. Serum free insulin and plasma glucose concentrations were measured for 10 hours and plasma Pramlintide concentrations for 5 hours after injection. Results. Blood samples were collected from a total of 51 patients. All treatments involving mixtures were comparable to separate injections with respect to the area under the concentration-versus-time curve (AUC) and the maximum concentration ( C max) of serum free insulin. There were some minor differences in the AUC and C max of Pramlintide. No injection-site reactions or other unexpected adverse events were observed. Conclusion. Mixing Pramlintide with short- or long-acting insulin in the same syringe before subcutaneous injection did not affect the pharmacodynamics of glucose or the pharmacokinetics of insulin or Pramlintide in a clinically significant manner.
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adjunctive therapy with Pramlintide lowers hba1c without concomitant weight gain and increased risk of severe hypoglycemia in patients with type 1 diabetes approaching glycemic targets
Experimental and Clinical Endocrinology & Diabetes, 2005Co-Authors: Robert E Ratner, Mark Fineman, Susan Strobel, Orville G Kolterman, David G Maggs, Larry Z Shen, Fred W Whitehouse, Christian WeyerAbstract:AIMS In long-term clinical trials in patients with type 1 diabetes spanning a wide range of HbA1c, addition of Pramlintide to existing insulin regimens led to reductions in HbA1c that were accompanied by weight loss and no increase in overall severe hypoglycemia event rates. Given that weight gain and increased hypoglycemia risk contribute to the difficulty of attaining HbA1c targets (<7 %), the question arose whether Pramlintide could benefit patients approaching, but not reaching glycemic targets with insulin alone. To address this question, we conducted a pooled analysis from 3 long-term clinical trials, including all patients with an entry HbA1c between 7.0 % and 8.5 %. METHODS Within the subset of patients with an entry HbA1c between 7.0 % and 8.5 % (approximately 28 % of all patients enrolled in the 3 studies), 196 were treated with placebo + insulin (baseline HbA1c 7.9+/-0.4 %, body weight 76.0+/-14.3 kg [mean+/-SD]) and 281 with Pramlintide+insulin (baseline HbA1c 7.9+/-0.4 %, body weight 75.4+/-13.1 kg). Endpoints included placebo-corrected changes from baseline to week 26 in HbA1c, body weight, and the event rate of severe hypoglycemia. RESULTS Adjunctive therapy with Pramlintide resulted in significant reductions in HbA1c and body weight from baseline to week 26 (0.3 % and 1.8 kg, placebo-corrected treatment differences, respectively, both p
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amylin replacement with Pramlintide as an adjunct to insulin therapy improves long term glycaemic and weight control in type 1 diabetes mellitus a 1 year randomized controlled trial
Diabetic Medicine, 2004Co-Authors: Robert E Ratner, Mark Fineman, Susan Strobel, Christian Weyer, David G Maggs, Larry Z Shen, R Dickey, Orville G KoltermanAbstract:AIMS The autoimmune-mediated destruction of pancreatic beta-cells in Type 1 diabetes mellitus renders patients deficient in two glucoregulatory peptide hormones, insulin and amylin. With insulin replacement alone, most patients do not achieve glycaemic goals. We aimed to determine the long-term efficacy and safety of adjunctive therapy with Pramlintide, a synthetic human amylin analogue, in patients with Type 1 diabetes. METHODS In a double-blind, placebo-controlled, parallel-group, multicentre study, 651 patients with Type 1 diabetes (age 41 +/- 13 years, HbA(1c) 8.9 +/- 1.0%, mean +/- sd) were randomized to mealtime injections of placebo or varying doses of Pramlintide, in addition to their insulin therapy, for 52 weeks. RESULTS Addition of Pramlintide [60 microg three times daily (TID) or four times daily (QID)] to insulin led to significant reductions in HbA(1c) from baseline to Week 52 of 0.29% (P < 0.011) and 0.34% (P < 0.001), respectively, compared with a 0.04% reduction in placebo group. Three times the proportion of Pramlintide- than placebo-treated patients achieved an HbA(1c) of < 7%. The greater reduction in HbA(1c) with Pramlintide was achieved without an increase in concomitant insulin use and was accompanied by a significant reduction in body weight from baseline to Week 52 of 0.4 kg in the 60 microg TID (P < 0.027) or QID (P < 0.040) Pramlintide treatment groups, compared with a 0.8-kg gain in body weight in the placebo group. The most common adverse event in Pramlintide-treated patients was transient, mild-to-moderate nausea. CONCLUSIONS These results show that mealtime amylin replacement with Pramlintide, as an adjunct to insulin therapy, improves long-term glycaemic and weight control in patients with Type 1 diabetes.