James Malone - Academia.edu (original) (raw)

Papers by James Malone

Research paper thumbnail of 1.6 Exenatide BID vs. Insulin Lispro TIDM Added to Titrated Insulin Glargine QD in Metformin-Treated T2DM Patients Resulted in Similar Glycemic Control but Weight Loss and Less Hypoglycemia: The 4B Study (70-OR)

Nederlands Tijdschrift voor Diabetologie, 2013

ABSTRACT Addition of prandial to basal insulin is the current strategy when A1C is elevated above... more ABSTRACT Addition of prandial to basal insulin is the current strategy when A1C is elevated above target, but at the cost of hypoglycemia (hypo) and weight gain. We examined Basal insulin glargine (IG) + Exenatide BID Treatment (BET) or Basal IG + mealtime Bolus insulin lispro (IL) Treatment (BBT) in patients (pts) on metformin uncontrolled on intensified IG.

Research paper thumbnail of Patient acceptance and reliability of new Humulin/Humalog 3.0 ml prefilled insulin pen in ten Croatian diabetes centres

Medical science monitor : international medical journal of experimental and clinical research, 2002

The objective of this study was to assess feature preferences, patient acceptance, reliability, a... more The objective of this study was to assess feature preferences, patient acceptance, reliability, and safety of the new Lilly Humulin/Humalog 3.0 ml prefilled insulin pen in a clinical setting. A total of 330 patients in Croatia with type 1 or type 2 diabetes mellitus who required at least one injection of insulin per day were treated with Humulin 30/70 or Humalog for 4 to 6 weeks using the new prefilled pen. Questionnaires concerning various aspects of the pen performance were administered at endpoint. The features of the Lilly 3.0 ml pen device ranked most highly by patients (% of excellent or good ratings) were cartridge visibility (93%), attaching/replacing needles (93%), ease of dose correction (92%), checking insulin flow (90%) and dialling of insulin dose (89%). Features of the pen device rated most highly by patients in comparison with the delivery systems used before the study and the percentage of patients rating those features as much better or better were ease of dose corr...

Research paper thumbnail of Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes

Diabetes care, 2014

Mealtime insulin is commonly added to manage hyperglycemia in type 2 diabetes when basal insulin ... more Mealtime insulin is commonly added to manage hyperglycemia in type 2 diabetes when basal insulin is insufficient. However, this complex regimen is associated with weight gain and hypoglycemia. This study compared the efficacy and safety of exenatide twice daily or mealtime insulin lispro in patients inadequately controlled by insulin glargine and metformin despite up-titration. In this 30-week, open-label, multicenter, randomized, noninferiority trial with 12 weeks prior insulin optimization, 627 patients with insufficient postoptimization glycated hemoglobin A1c (HbA1c) were randomized to exenatide (10-20 µg/day) or thrice-daily mealtime lispro titrated to premeal glucose of 5.6-6.0 mmol/L, both added to insulin glargine (mean 61 units/day at randomization) and metformin (mean 2,000 mg/day). Randomization HbA1c and fasting glucose (FG) were 8.3% (67 mmol/mol) and 7.1 mmol/L for exenatide and 8.2% (66 mmol/mol) and 7.1 mmol/L for lispro. At 30 weeks postrandomization, mean HbA1c cha...

Research paper thumbnail of Exenatide once weekly for the treatment of type 2 diabetes

Expert Opinion on Investigational Drugs, 2009

Exenatide is the first glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatmen... more Exenatide is the first glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes mellitus (T2DM). Exenatide lowers blood glucose through multiple mechanisms, including enhancement of glucose-dependent insulin secretion, suppression of excess glucagon secretion, reduction of food intake and slowing of gastric emptying. The current formulation of exenatide requires twice-daily dosing (exenatide BID), and an extended-release formulation of exenatide is now in development for use as a once-weekly injection (exenatide QW). The purpose of this report is to review the most current clinical data on the development of exenatide QW for the treatment of T2DM. In clinical trials, exenatide QW significantly improved glycemic control, resulted in patient weight loss, and was well tolerated in patients with T2DM. In a head-to-head clinical trial, exenatide QW caused greater improvements in glycemic control and was better tolerated than exenatide BID. Given the rapidly increasing prevalence of diabetes and obesity worldwide, exenatide QW is a promising development candidate for the treatment of T2DM.

Research paper thumbnail of Exenatide effects on glucose metabolism and metabolic disorders common to overweight and obese patients with type 2 diabetes

Drug Development Research, 2006

... Author Information. 1 Eli Lilly and Company, Indianapolis, Indiana. 2 Amylin Pharmaceuticals,... more ... Author Information. 1 Eli Lilly and Company, Indianapolis, Indiana. 2 Amylin Pharmaceuticals, San Diego, California. Email: James K. Malone (jkmalone@lilly.com). *Correspondence: James K. Malone, Eli Lilly and Company, Indianapolis, IN. Publication History. ...

Research paper thumbnail of Twice-daily pre-mixed insulin rather than basal insulin therapy alone results in better overall glycaemic control in patients with Type 2 diabetes

Diabetic Medicine, 2005

To compare the glycaemic control of an insulin lispro mixture (25% insulin lispro and 75% NPL) tw... more To compare the glycaemic control of an insulin lispro mixture (25% insulin lispro and 75% NPL) twice daily in combination with metformin to that of once-daily insulin glargine plus metformin in patients with Type 2 diabetes inadequately controlled with intermediate insulin, or insulin plus oral agent(s) combination therapy.

Research paper thumbnail of DURATION-2: efficacy and safety of switching from maximum daily sitagliptin or pioglitazone to once-weekly exenatide

Diabetic Medicine, 2011

In the initial 26-week, double-blind, double-dummy assessment period of the DURATION-2 trial in p... more In the initial 26-week, double-blind, double-dummy assessment period of the DURATION-2 trial in patients with Type 2 diabetes on metformin, the once-weekly glucagon-like peptide 1 (GLP-1) receptor agonist exenatide once-weekly resulted in greater HbA 1c improvement and weight reduction compared with maximum approved daily doses of sitagliptin or pioglitazone. This subsequent, 26-week, open-label, uncontrolled assessment period evaluated the safety and efficacy of (i) continued exenatide once-weekly treatment and (ii) switching from sitagliptin or pioglitazone to exenatide once-weekly.

Research paper thumbnail of Therapy after single oral agent failure: adding a second oral agent or an insulin mixture?

Diabetes Research and Clinical Practice, 2003

to compare the glycemic response to an insulin lispro mixture (25% insulin lispro and 75% NPL) tw... more to compare the glycemic response to an insulin lispro mixture (25% insulin lispro and 75% NPL) twice daily plus metformin (Mix25+M) with glibenclamide plus metformin (G+M), in patients with type 2 diabetes inadequately controlled with a single oral agent. 597 patients treated in a randomized, open-label, 16-week parallel study. Variables evaluated: hemoglobin A1C (A1C), patient symptoms, hypoglycemia rate (episodes/patient/30 days), and incidence (% patients experiencing > or =1 episode). For a subset of patients (N=120), fasting, 1-h, and 2-h postprandial plasma glucose (FPG, 1-h ppPG, 2-h ppPG) in response to a standardized test meal (STM) and self-monitored blood glucose (BG) profiles were measured. improved A1C at endpoint for both groups, and A1C changes from baseline to endpoint were not significantly different between treatments (Mix25+M, -1.87+/-1.35% vs. G+M, -1.98+/-1.28%; p=0.288). Among patients completing STM; endpoint 2-h ppPG was significantly lower with Mix25+M (9.05+/-3.32 mmol/l vs. 12.31+/-3.65 mmol/l; p<0.001), as was 2-h ppPG excursion (2-h ppPGex)(0.38+/-3.23 mmol/l vs. 2.88+/-1.98 mmol/l; p<0.001). Percentage of patients achieving postprandial BG targets (<10 mmol/l) at endpoint was significantly greater with Mix25+M (80% vs. 48%; p<0.001). Although, overall hypoglycemia rates were similar, percentage of patients experiencing and rate of nocturnal hypoglycemia was less with Mix25+M (1% vs. 5%; p<0.01, and 0.01 vs. 0.08 episodes/pt/30 d; p=0.007). Patients reported less polyuria with Mix25+M (p<0.001). in patients with type 2 diabetes failing on metformin or a sulfonylurea, Mix25+M provided similar overall glycemic control, lower ppPG, reduced nocturnal hypoglycemia, and fewer hyperglycemic symptoms compared to G+M.

Research paper thumbnail of Use of insulin lispro (Humalog®) mixtures in the elderly provides comparable safety to that of human insulin mixtures

Diabetes Research and Clinical Practice, 2000

Poster Discussion 2 symptoms. Older participants bad poorer metabolic control, more frequent visi... more Poster Discussion 2 symptoms. Older participants bad poorer metabolic control, more frequent visits was associated with poorer control, and greater perceived treatment effectiveness was associated with better metabolic control. Neither perceived barriers or self-efficacy were associated with metabolic control. Using multiple regression, perceived treatment effectiveness (b = 0.37) and number of visit of the previous year (b = 0.37) were the only significant predictors of metabolic control (R2 = 53; 9.38; p < 0.001). Perceived treatment effectiveness mediated the association between age and metabolic control. Interaction terms between treatment effectiveness, barriers and self-efficacy were computed, and although correlated with metabolic control, were not significant in multiple regression analysis. Conclusion: Beliefs about the effectiveness of treatment are of primary importance in the motivation of young peoples self-care behaviour.

Research paper thumbnail of Patient Acceptability of a New 3.0ml Pre-filled Insulin Pen

Current Medical Research and Opinion, 2000

The objective of these two studies was to assess patient acceptance and feature preferences of th... more The objective of these two studies was to assess patient acceptance and feature preferences of the new Lilly 3.0 ml pre-filled pen. A total of 701 patients with diabetes mellitus, who required insulin, were treated for 4-6 weeks with the pre-filled pen. Patient acceptance and treatment preferences were assessed by a questionnaire completed at the end of the study period. Patients with type 1 or type 2 diabetes mellitus from South Africa (n = 371) and Croatia (n = 330) were enrolled in the study. The mean age was 51.6 years (range: 18-81), and gender was 359 males and 342 females. Prior to the study, patients in South Africa (SA) had used the Novo Actraphane (Novo Nordisk, Bagsvaerd, Denmark) pen set, and patients in Croatia (C) had used NovoPen 1 or 2 (Novo Nordisk, Bagsvaerd, Denmark) (38.8%), NovoPen 3 (Novo Nordisk, Bagsvaerd, Denmark) (28.8%), B-D Pen (Becton-Dickinson, Franklin Lakes, New Jersey, USA) (18.8%), needle/syringe (10.0%), oral hypoglycaemic agents (2.1%), or unknown (1.5%). The new Lilly 3.0 ml pre-filled pen features that were rated by respondents as good to excellent on a five-point rating scale included: cartridge visibility (C = 94%, SA = 83%), ease of dose correction (C = 92%, SA = 85%), dialling of the dose (C = 89%, SA = 81%), turning of the dose knob (C = 84%, SA = 82%) and attaching needles (C = 92%, SA = 78%). Most respondents (C = 78%, SA = 75%) preferred single-unit versus two-unit dosage increments. Overall, 76% of patients in Croatia and 80% in South Africa preferred the Lilly 3.0 ml pre-filled pen to their previous delivery device; 84% and 87% of patients, respectively, would recommend the pen to another patient. Also, the majority of patients in both trials rated the new Lilly 3.0 ml pre-filled pen as being more convenient and easier to use, and indicated that it represented a significant or modest improvement over their previous insulin injection method. The results of this study confirm that the new Lilly 3.0 ml pre-filled pen is widely accepted and preferred by patients using both reusable and pre-filled devices.

Research paper thumbnail of Functionality and acceptability of a new electronic insulin injection pen with a memory feature*

Current Medical Research and Opinion, 2006

The HumaPen Memoir (HPM) is a new reusable insulin injection pen. It possesses an electronic comp... more The HumaPen Memoir (HPM) is a new reusable insulin injection pen. It possesses an electronic component so that 16 insulin doses are stored in the memory. This study&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s aim was to evaluate the functionality of the device (i.e., ability to deliver a set dose of insulin), its impact on patient safety, and patient/healthcare professional (HCP) acceptance. In this 6-10-week (3 visit) multinational, multi-centre, open-label, single-arm outpatient study, participants with type 1 or type 2 diabetes were assigned to inject either their prandial or basal insulin dose using the HPM and instructed to record all complaints with the study pen or user manual. Investigators submitted a complaint form to the sponsor for each participant complaint, and for adverse events (AEs) potentially related to the study pen. Where a complaint was possibly related to a pen malfunction, the pen was returned to the sponsor for assessment. Participant/HCP acceptance of the HPM was evaluated using questionnaires. Of the 300 participants (mean age 52 [SD 15] years), 58% were male and 62% had type 2 diabetes. The mean duration of pre-study pen use was 7 years. The average exposure to the HPM was 8.2 (SD 1.6) weeks. Overall, 314 study pens were used (14 were replacements). Functional complaints were reported for 24 devices (7.6%), of which 8 (2.5%) were permanent electronic failures, and 15 (4.8%) were user-related (1 pen not returned for assessment). None of these functional issues resulted in a serious AE. Non-functional complaints were reported for 33 devices (10.5%). There were no pen-related hypoglycemic episodes and 2 pen-related hyperglycemic episodes were reported. The majority of participants (81.4%) preferred the HPM over their pre-study pen. The new insulin pen was generally rated higher than the pre-study pen for pen features and tasks associated with everyday pen use. No major functional issue of the HPM resulting in a serious AE was reported in this study. Based on the study results this new insulin pen demonstrated a favorable benefit-risk profile.

Research paper thumbnail of Combined therapy with insulin lispro mix 75/25 plus metformin or insulin glargine plus metformin: A 16-week, randomized, open-label, crossover study in patients with type 2 diabetes beginning insulin therapy

Clinical Therapeutics, 2004

This study aimed to assess glycemic response to a mixture of 75% insulin lispro protamine suspens... more This study aimed to assess glycemic response to a mixture of 75% insulin lispro protamine suspension and 25% insulin lispro (Mix 75/25) BID plus metformin versus insulin glargine QD plus metformin in patients with type 2 diabetes mellitus (DM). Adults new to insulin therapy were enrolled in a multicenter, randomized, prospective, open-label, crossover study with 16 weeks on each treatment. Variables included glycosylated hemoglobin (HbA(1c)), hypoglycemia rate, fasting blood glucose (FBG), 2-hour postprandial blood glucose (ppBG), and rise in blood glucose after meals. One hundred five patients (mean age, 55 years) were randomized. There was no difference in baseline mean values for either treatment sequence group for body mass index, duration of DM, or HbA(1c). Ninety-five patients completed the study and 67 were included in the efficacy analysis. Mix 75/25 was associated with lower mean (SD) HbA(1c) at end point (7.4% [1.1%] vs 7.8% [1.1%]; P = 0.002). More patients using Mix 75/25 achieved target HbA(1c) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =7.0% (42% [30/71] vs 18% [13/71]; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). With Mix 75/25, the mean (SD) 2-hour ppBG was similar after lunch but lower after breakfast (156.4 [43.6] vs 171.1 [44.9] mg/dL; P = 0.012) and dinner (164.8 [42.5] mg/dL vs 193.8 [51.0] mg/dL; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), although FBG was higher (139.3 [36.6] mg/dL vs 123.9 [34.9] mg/dL; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Rise in ppBG was lower with Mix 75/25 after breakfast (16.9 [47.0] mg/dL vs 47.4 [34.8] mg/dL; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and dinner (14.2 [44.1] mg/dL vs 45.9 [41.3] mg/dL; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Gain in mean (SD) body weight was greater with Mix 75/25 than insulin glargine (2.3 [4.0] kg vs 1.6 [4.0] kg; P = 0.006). For all randomized patients, mean (SD) hypoglycemia rates were lower with insulin glargine (0.68 [1.38] vs 0.39 [1.24] episodes/patient per 30 days; P = 0.041), although nocturnal hypoglycemia was similar. In this study population, Mix 75/25 plus metformin was associated with lower HbA(1c) than insulin glargine plus metformin, smaller rise in ppBG after breakfast and dinner, and higher proportion of patients achieving HbA(1c) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =7.0%, with a slight increase in overall (but not nocturnal) hypoglycemia.

Research paper thumbnail of Improved postprandial glycemic control with humalog® mix75/25™ after a standard test meal in patients with type 2 diabetes mellitus

Clinical Therapeutics, 2000

This double-blind study was designed to compare the postprandial glucodynamic profile of Humalog ... more This double-blind study was designed to compare the postprandial glucodynamic profile of Humalog Mix75/25, a new premixed insulin analogue containing 75% neutral protamine lispro and 25% insulin lispro with that of human insulin 70/30 (70% neutral protamine Hagedorn insulin and 30% regular human insulin) in patients with type 2 diabetes mellitus. Insulin lispro Mix75/25 (Mix75/25) is the first available insulin formulation in which both the rapid-acting and basal components are insulin analogues. This randomized, multicenter, double-blind, crossover study monitored patients&#39; postprandial glucodynamic response to Mix75/25 and human insulin 70/30 (70/30) after a standard test meal. Eighty-four patients with type 2 diabetes participated in this study and were randomly assigned to 1 of 2 treatment sequence groups. Patients received an identical test meal on 4 occasions, completing 2 test meals for each treatment. Equal doses of Mix75/25 or 70/30 were administered 5 minutes before each of the 2 test meals, with doses individualized for each patient. Blood samples were collected for 4 hours after the meal for measurement of plasma glucose. From these plasma glucose measurements, fasting plasma glucose, 2-hour postprandial glucose (2pp), 2-hour postprandial glucose excursion (2pp(ex)), maximum glucose excursion (Gex(max)), the area under the glucose concentration versus time curve from 0 to 4 hours (AUC4), and the area under the glucose excursion versus time curve from 0 to 4 hours (AUCex4) were calculated. Because of significant differences in the baseline fasting plasma glucose levels between Mix75/25 and 70/30 (Mix75/25: 8.9+/-2.2 mmol/L [160.2+/-39.6 mg/dL]; 70/30: 8.6+/-1.9 mmol/L [154+/-34 mg/dL), analyses of the excursion parameters provide a truer comparison of the glucodynamic response between insulin formulations. Mix75/25 resulted in significantly lower values for 2pp(ex) (3.35+/-2.28 vs 4.13+/-2.26 mmol/L), Gex(max) (4.51+/-1.88 vs 5.19+/-1.98 mmol/L), and AUCex4 (8.01+/-7.02 vs 10.6+/-6.47 mmol x h/L) compared with 70/30. In patients with type 2 diabetes mellitus, premeal injection of Mix75/25 resulted in better postprandial glycemic control than did premeal injection of 70/30 in the 4 hours after a standard meal. Mix75/25 is a valuable option for managing postprandial blood glucose in patients with type 2 diabetes mellitus who require insulin.

Research paper thumbnail of Prandial Premixed Insulin Analogue Regimens Versus Basal Insulin Analogue Regimens in the Management of Type 2 Diabetes: An Evidence-Based Comparison

Clinical Therapeutics, 2007

Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which ins... more Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which insulin deficiency is one of the core defects. When patients with T2D are unable to achieve glycemic goals with diet and oral antihyperglycemic medications, a common starting insulin regimen consists of basal or premixed insulin added to oral antihyperglycemic medications. When glycemic goals are not achieved with the initial insulin regimen, a basal-bolus regimen is necessary. This article reviews clinical-trial data on the efficacy and safety profile of prandial premixed insulin analogues (insulin aspart and insulin lispro) compared with basal insulin analogues (insulin glargine, insulin detemir, and insulin lispro protamine suspension), with or without a prandial insulin analogue, in the management of T2D. A systematic search of Ovid, MEDLINE, and EMBASE (1995-2007) was performed to identify published randomized controlled trials comparing prandial premixed insulin analogues with basal insulin analogues, with or without prandial insulin, in patients with T2D. The search terms were premixed insulin analogues, premixed insulin, biphasic insulin aspart, insulin aspart 70/30, insulin aspart 50/50, premixed insulin lispro, insulin lispro 75/25, insulin lispro 50/50, glargine, and detemir. Abstracts presented at the 2005 and 2006 meetings of the American Diabetes Association and the European Association for the Study of Diabetes and bibliographies of the identified studies were also reviewed. Predetermined criteria for study inclusion were treatment duration of at least 12 weeks, T2D diagnosed using valid criteria, use of a basal insulin analogue (with or without rapid-acting insulin) as a study comparator, and use of well-accepted end points (eg, glycosylated hemoglobin [HbA1c], hypoglycemia, preprandial and postprandial blood glucose). Of the identified randomized controlled trials, 3 studies compared premixed insulin analogues containing 70% or 75% basal and 30% or 25% rapid-acting insulin analogue with basal insulin analogues only, and 3 studies evaluated premixed insulin analogues containing 50% basal and 50% rapid-acting insulin analogue with basal insulin analogues only. Use of prandial premixed insulin analogues was associated with better overall and postprandial glycemic control. In the studies that compared twice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA1c ranged from -1.00% to -2.79% and from -0.42% to -2.36%, respectively (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). In the studies that compared thrice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA1c ranged from -0.72% to -1.2% and from -0.3% to -0.75%, respectively (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). These results were achieved with some increase in overall hypoglycemia, but not in nocturnal or severe hypoglycemia. Doses of the premixed insulin analogues were adjusted during the titration period to achieve glycemic goals. The results of this systematic review suggest that regimens consisting of prandial premixed insulin analogues, which provide both basal and prandial insulin coverage, may be used as an initial insulin regimen in patients with T2D to enable better overall, preprandial, and postprandial glycemic control compared with a basal insulin analogue regimen alone. Premixed insulin analogues are an effective option for initiating and intensifying insulin therapy in patients with T2D.

Research paper thumbnail of Effect of exenatide on heart rate and blood pressure in subjects with type 2 diabetes mellitus: a double-blind, placebo-controlled, randomized pilot study

Cardiovascular Diabetology, 2010

Background: Cardiovascular effects of glucose-lowering agents are of increasing interest. Our aim... more Background: Cardiovascular effects of glucose-lowering agents are of increasing interest. Our aim was to assess the effects of the glucagon-like peptide-1 receptor agonist exenatide on heart rate (HR) and blood pressure (BP) in subjects with type 2 diabetes mellitus (T2DM). Methods: In this double-blind, placebo-controlled trial, subjects with T2DM on metformin and/or a thiazolidinedione were randomized to receive exenatide (5 μg for 4 weeks followed by 10 μg) or placebo BID for 12 weeks. Heart rate and BP were assessed with 24-hour ambulatory BP monitoring. The primary measure was change from baseline in mean 24-hour HR.

Research paper thumbnail of A comparison of insulin lispro Mix25™ and human insulin 30/70 in the treatment of type 2 diabetes during Ramadan

Diabetes Research and Clinical Practice, 2003

To compare insulin lispro Mix25 and human insulin 30/70 with regard to their effect on morning an... more To compare insulin lispro Mix25 and human insulin 30/70 with regard to their effect on morning and evening postprandial glucose (PPG) control, and on average daily blood-glucose (BG), in patients with Type 2 diabetes who wish to fast during Ramadan. Insulin lispro Mix25 and human insulin 30/70 were compared in an open-label, multicenter, randomised, crossover study involving 151 patients. Each treatment period had a duration of 14 days during which the patients self-monitored their BG before and 2 h after the main meals on any 3 days within the last 5 days of each treatment period. The 2 h PPG excursion following the main evening meal after sunset was significantly lower with insulin lispro Mix25 (3.4+/-2.9 mmol/l) compared with human insulin 30/70 (4.0+/-3.2 mmol/l, P=0.007). The evening pre-meal fasting BG values were also lower with insulin lispro Mix25 (7.1+/-2.2 mmol/l) versus human insulin 30/70 (7.5+/-2.6 mmol/l, P=0.034). The average daily BG concentration was 9.5+/-2.4 mmol/l during treatment with insulin lispro Mix25 versus 10.1+/-2.5 mmol/l with human insulin 30/70 given in identical doses (P=0.004). When compared with human insulin 30/70, treatment of insulin-requiring Type 2 patients with insulin lispro Mix25 during Ramadan resulted in better average daily glycaemia, and better BG control before and after the evening meal. Insulin lispro Mix25 should be considered as a therapeutic option during Ramadan.

Research paper thumbnail of 1.6 Exenatide BID vs. Insulin Lispro TIDM Added to Titrated Insulin Glargine QD in Metformin-Treated T2DM Patients Resulted in Similar Glycemic Control but Weight Loss and Less Hypoglycemia: The 4B Study (70-OR)

Nederlands Tijdschrift voor Diabetologie, 2013

ABSTRACT Addition of prandial to basal insulin is the current strategy when A1C is elevated above... more ABSTRACT Addition of prandial to basal insulin is the current strategy when A1C is elevated above target, but at the cost of hypoglycemia (hypo) and weight gain. We examined Basal insulin glargine (IG) + Exenatide BID Treatment (BET) or Basal IG + mealtime Bolus insulin lispro (IL) Treatment (BBT) in patients (pts) on metformin uncontrolled on intensified IG.

Research paper thumbnail of Patient acceptance and reliability of new Humulin/Humalog 3.0 ml prefilled insulin pen in ten Croatian diabetes centres

Medical science monitor : international medical journal of experimental and clinical research, 2002

The objective of this study was to assess feature preferences, patient acceptance, reliability, a... more The objective of this study was to assess feature preferences, patient acceptance, reliability, and safety of the new Lilly Humulin/Humalog 3.0 ml prefilled insulin pen in a clinical setting. A total of 330 patients in Croatia with type 1 or type 2 diabetes mellitus who required at least one injection of insulin per day were treated with Humulin 30/70 or Humalog for 4 to 6 weeks using the new prefilled pen. Questionnaires concerning various aspects of the pen performance were administered at endpoint. The features of the Lilly 3.0 ml pen device ranked most highly by patients (% of excellent or good ratings) were cartridge visibility (93%), attaching/replacing needles (93%), ease of dose correction (92%), checking insulin flow (90%) and dialling of insulin dose (89%). Features of the pen device rated most highly by patients in comparison with the delivery systems used before the study and the percentage of patients rating those features as much better or better were ease of dose corr...

Research paper thumbnail of Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes

Diabetes care, 2014

Mealtime insulin is commonly added to manage hyperglycemia in type 2 diabetes when basal insulin ... more Mealtime insulin is commonly added to manage hyperglycemia in type 2 diabetes when basal insulin is insufficient. However, this complex regimen is associated with weight gain and hypoglycemia. This study compared the efficacy and safety of exenatide twice daily or mealtime insulin lispro in patients inadequately controlled by insulin glargine and metformin despite up-titration. In this 30-week, open-label, multicenter, randomized, noninferiority trial with 12 weeks prior insulin optimization, 627 patients with insufficient postoptimization glycated hemoglobin A1c (HbA1c) were randomized to exenatide (10-20 µg/day) or thrice-daily mealtime lispro titrated to premeal glucose of 5.6-6.0 mmol/L, both added to insulin glargine (mean 61 units/day at randomization) and metformin (mean 2,000 mg/day). Randomization HbA1c and fasting glucose (FG) were 8.3% (67 mmol/mol) and 7.1 mmol/L for exenatide and 8.2% (66 mmol/mol) and 7.1 mmol/L for lispro. At 30 weeks postrandomization, mean HbA1c cha...

Research paper thumbnail of Exenatide once weekly for the treatment of type 2 diabetes

Expert Opinion on Investigational Drugs, 2009

Exenatide is the first glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatmen... more Exenatide is the first glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes mellitus (T2DM). Exenatide lowers blood glucose through multiple mechanisms, including enhancement of glucose-dependent insulin secretion, suppression of excess glucagon secretion, reduction of food intake and slowing of gastric emptying. The current formulation of exenatide requires twice-daily dosing (exenatide BID), and an extended-release formulation of exenatide is now in development for use as a once-weekly injection (exenatide QW). The purpose of this report is to review the most current clinical data on the development of exenatide QW for the treatment of T2DM. In clinical trials, exenatide QW significantly improved glycemic control, resulted in patient weight loss, and was well tolerated in patients with T2DM. In a head-to-head clinical trial, exenatide QW caused greater improvements in glycemic control and was better tolerated than exenatide BID. Given the rapidly increasing prevalence of diabetes and obesity worldwide, exenatide QW is a promising development candidate for the treatment of T2DM.

Research paper thumbnail of Exenatide effects on glucose metabolism and metabolic disorders common to overweight and obese patients with type 2 diabetes

Drug Development Research, 2006

... Author Information. 1 Eli Lilly and Company, Indianapolis, Indiana. 2 Amylin Pharmaceuticals,... more ... Author Information. 1 Eli Lilly and Company, Indianapolis, Indiana. 2 Amylin Pharmaceuticals, San Diego, California. Email: James K. Malone (jkmalone@lilly.com). *Correspondence: James K. Malone, Eli Lilly and Company, Indianapolis, IN. Publication History. ...

Research paper thumbnail of Twice-daily pre-mixed insulin rather than basal insulin therapy alone results in better overall glycaemic control in patients with Type 2 diabetes

Diabetic Medicine, 2005

To compare the glycaemic control of an insulin lispro mixture (25% insulin lispro and 75% NPL) tw... more To compare the glycaemic control of an insulin lispro mixture (25% insulin lispro and 75% NPL) twice daily in combination with metformin to that of once-daily insulin glargine plus metformin in patients with Type 2 diabetes inadequately controlled with intermediate insulin, or insulin plus oral agent(s) combination therapy.

Research paper thumbnail of DURATION-2: efficacy and safety of switching from maximum daily sitagliptin or pioglitazone to once-weekly exenatide

Diabetic Medicine, 2011

In the initial 26-week, double-blind, double-dummy assessment period of the DURATION-2 trial in p... more In the initial 26-week, double-blind, double-dummy assessment period of the DURATION-2 trial in patients with Type 2 diabetes on metformin, the once-weekly glucagon-like peptide 1 (GLP-1) receptor agonist exenatide once-weekly resulted in greater HbA 1c improvement and weight reduction compared with maximum approved daily doses of sitagliptin or pioglitazone. This subsequent, 26-week, open-label, uncontrolled assessment period evaluated the safety and efficacy of (i) continued exenatide once-weekly treatment and (ii) switching from sitagliptin or pioglitazone to exenatide once-weekly.

Research paper thumbnail of Therapy after single oral agent failure: adding a second oral agent or an insulin mixture?

Diabetes Research and Clinical Practice, 2003

to compare the glycemic response to an insulin lispro mixture (25% insulin lispro and 75% NPL) tw... more to compare the glycemic response to an insulin lispro mixture (25% insulin lispro and 75% NPL) twice daily plus metformin (Mix25+M) with glibenclamide plus metformin (G+M), in patients with type 2 diabetes inadequately controlled with a single oral agent. 597 patients treated in a randomized, open-label, 16-week parallel study. Variables evaluated: hemoglobin A1C (A1C), patient symptoms, hypoglycemia rate (episodes/patient/30 days), and incidence (% patients experiencing &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =1 episode). For a subset of patients (N=120), fasting, 1-h, and 2-h postprandial plasma glucose (FPG, 1-h ppPG, 2-h ppPG) in response to a standardized test meal (STM) and self-monitored blood glucose (BG) profiles were measured. improved A1C at endpoint for both groups, and A1C changes from baseline to endpoint were not significantly different between treatments (Mix25+M, -1.87+/-1.35% vs. G+M, -1.98+/-1.28%; p=0.288). Among patients completing STM; endpoint 2-h ppPG was significantly lower with Mix25+M (9.05+/-3.32 mmol/l vs. 12.31+/-3.65 mmol/l; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), as was 2-h ppPG excursion (2-h ppPGex)(0.38+/-3.23 mmol/l vs. 2.88+/-1.98 mmol/l; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Percentage of patients achieving postprandial BG targets (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10 mmol/l) at endpoint was significantly greater with Mix25+M (80% vs. 48%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). Although, overall hypoglycemia rates were similar, percentage of patients experiencing and rate of nocturnal hypoglycemia was less with Mix25+M (1% vs. 5%; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01, and 0.01 vs. 0.08 episodes/pt/30 d; p=0.007). Patients reported less polyuria with Mix25+M (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). in patients with type 2 diabetes failing on metformin or a sulfonylurea, Mix25+M provided similar overall glycemic control, lower ppPG, reduced nocturnal hypoglycemia, and fewer hyperglycemic symptoms compared to G+M.

Research paper thumbnail of Use of insulin lispro (Humalog®) mixtures in the elderly provides comparable safety to that of human insulin mixtures

Diabetes Research and Clinical Practice, 2000

Poster Discussion 2 symptoms. Older participants bad poorer metabolic control, more frequent visi... more Poster Discussion 2 symptoms. Older participants bad poorer metabolic control, more frequent visits was associated with poorer control, and greater perceived treatment effectiveness was associated with better metabolic control. Neither perceived barriers or self-efficacy were associated with metabolic control. Using multiple regression, perceived treatment effectiveness (b = 0.37) and number of visit of the previous year (b = 0.37) were the only significant predictors of metabolic control (R2 = 53; 9.38; p < 0.001). Perceived treatment effectiveness mediated the association between age and metabolic control. Interaction terms between treatment effectiveness, barriers and self-efficacy were computed, and although correlated with metabolic control, were not significant in multiple regression analysis. Conclusion: Beliefs about the effectiveness of treatment are of primary importance in the motivation of young peoples self-care behaviour.

Research paper thumbnail of Patient Acceptability of a New 3.0ml Pre-filled Insulin Pen

Current Medical Research and Opinion, 2000

The objective of these two studies was to assess patient acceptance and feature preferences of th... more The objective of these two studies was to assess patient acceptance and feature preferences of the new Lilly 3.0 ml pre-filled pen. A total of 701 patients with diabetes mellitus, who required insulin, were treated for 4-6 weeks with the pre-filled pen. Patient acceptance and treatment preferences were assessed by a questionnaire completed at the end of the study period. Patients with type 1 or type 2 diabetes mellitus from South Africa (n = 371) and Croatia (n = 330) were enrolled in the study. The mean age was 51.6 years (range: 18-81), and gender was 359 males and 342 females. Prior to the study, patients in South Africa (SA) had used the Novo Actraphane (Novo Nordisk, Bagsvaerd, Denmark) pen set, and patients in Croatia (C) had used NovoPen 1 or 2 (Novo Nordisk, Bagsvaerd, Denmark) (38.8%), NovoPen 3 (Novo Nordisk, Bagsvaerd, Denmark) (28.8%), B-D Pen (Becton-Dickinson, Franklin Lakes, New Jersey, USA) (18.8%), needle/syringe (10.0%), oral hypoglycaemic agents (2.1%), or unknown (1.5%). The new Lilly 3.0 ml pre-filled pen features that were rated by respondents as good to excellent on a five-point rating scale included: cartridge visibility (C = 94%, SA = 83%), ease of dose correction (C = 92%, SA = 85%), dialling of the dose (C = 89%, SA = 81%), turning of the dose knob (C = 84%, SA = 82%) and attaching needles (C = 92%, SA = 78%). Most respondents (C = 78%, SA = 75%) preferred single-unit versus two-unit dosage increments. Overall, 76% of patients in Croatia and 80% in South Africa preferred the Lilly 3.0 ml pre-filled pen to their previous delivery device; 84% and 87% of patients, respectively, would recommend the pen to another patient. Also, the majority of patients in both trials rated the new Lilly 3.0 ml pre-filled pen as being more convenient and easier to use, and indicated that it represented a significant or modest improvement over their previous insulin injection method. The results of this study confirm that the new Lilly 3.0 ml pre-filled pen is widely accepted and preferred by patients using both reusable and pre-filled devices.

Research paper thumbnail of Functionality and acceptability of a new electronic insulin injection pen with a memory feature*

Current Medical Research and Opinion, 2006

The HumaPen Memoir (HPM) is a new reusable insulin injection pen. It possesses an electronic comp... more The HumaPen Memoir (HPM) is a new reusable insulin injection pen. It possesses an electronic component so that 16 insulin doses are stored in the memory. This study&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s aim was to evaluate the functionality of the device (i.e., ability to deliver a set dose of insulin), its impact on patient safety, and patient/healthcare professional (HCP) acceptance. In this 6-10-week (3 visit) multinational, multi-centre, open-label, single-arm outpatient study, participants with type 1 or type 2 diabetes were assigned to inject either their prandial or basal insulin dose using the HPM and instructed to record all complaints with the study pen or user manual. Investigators submitted a complaint form to the sponsor for each participant complaint, and for adverse events (AEs) potentially related to the study pen. Where a complaint was possibly related to a pen malfunction, the pen was returned to the sponsor for assessment. Participant/HCP acceptance of the HPM was evaluated using questionnaires. Of the 300 participants (mean age 52 [SD 15] years), 58% were male and 62% had type 2 diabetes. The mean duration of pre-study pen use was 7 years. The average exposure to the HPM was 8.2 (SD 1.6) weeks. Overall, 314 study pens were used (14 were replacements). Functional complaints were reported for 24 devices (7.6%), of which 8 (2.5%) were permanent electronic failures, and 15 (4.8%) were user-related (1 pen not returned for assessment). None of these functional issues resulted in a serious AE. Non-functional complaints were reported for 33 devices (10.5%). There were no pen-related hypoglycemic episodes and 2 pen-related hyperglycemic episodes were reported. The majority of participants (81.4%) preferred the HPM over their pre-study pen. The new insulin pen was generally rated higher than the pre-study pen for pen features and tasks associated with everyday pen use. No major functional issue of the HPM resulting in a serious AE was reported in this study. Based on the study results this new insulin pen demonstrated a favorable benefit-risk profile.

Research paper thumbnail of Combined therapy with insulin lispro mix 75/25 plus metformin or insulin glargine plus metformin: A 16-week, randomized, open-label, crossover study in patients with type 2 diabetes beginning insulin therapy

Clinical Therapeutics, 2004

This study aimed to assess glycemic response to a mixture of 75% insulin lispro protamine suspens... more This study aimed to assess glycemic response to a mixture of 75% insulin lispro protamine suspension and 25% insulin lispro (Mix 75/25) BID plus metformin versus insulin glargine QD plus metformin in patients with type 2 diabetes mellitus (DM). Adults new to insulin therapy were enrolled in a multicenter, randomized, prospective, open-label, crossover study with 16 weeks on each treatment. Variables included glycosylated hemoglobin (HbA(1c)), hypoglycemia rate, fasting blood glucose (FBG), 2-hour postprandial blood glucose (ppBG), and rise in blood glucose after meals. One hundred five patients (mean age, 55 years) were randomized. There was no difference in baseline mean values for either treatment sequence group for body mass index, duration of DM, or HbA(1c). Ninety-five patients completed the study and 67 were included in the efficacy analysis. Mix 75/25 was associated with lower mean (SD) HbA(1c) at end point (7.4% [1.1%] vs 7.8% [1.1%]; P = 0.002). More patients using Mix 75/25 achieved target HbA(1c) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =7.0% (42% [30/71] vs 18% [13/71]; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). With Mix 75/25, the mean (SD) 2-hour ppBG was similar after lunch but lower after breakfast (156.4 [43.6] vs 171.1 [44.9] mg/dL; P = 0.012) and dinner (164.8 [42.5] mg/dL vs 193.8 [51.0] mg/dL; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), although FBG was higher (139.3 [36.6] mg/dL vs 123.9 [34.9] mg/dL; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Rise in ppBG was lower with Mix 75/25 after breakfast (16.9 [47.0] mg/dL vs 47.4 [34.8] mg/dL; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and dinner (14.2 [44.1] mg/dL vs 45.9 [41.3] mg/dL; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Gain in mean (SD) body weight was greater with Mix 75/25 than insulin glargine (2.3 [4.0] kg vs 1.6 [4.0] kg; P = 0.006). For all randomized patients, mean (SD) hypoglycemia rates were lower with insulin glargine (0.68 [1.38] vs 0.39 [1.24] episodes/patient per 30 days; P = 0.041), although nocturnal hypoglycemia was similar. In this study population, Mix 75/25 plus metformin was associated with lower HbA(1c) than insulin glargine plus metformin, smaller rise in ppBG after breakfast and dinner, and higher proportion of patients achieving HbA(1c) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =7.0%, with a slight increase in overall (but not nocturnal) hypoglycemia.

Research paper thumbnail of Improved postprandial glycemic control with humalog® mix75/25™ after a standard test meal in patients with type 2 diabetes mellitus

Clinical Therapeutics, 2000

This double-blind study was designed to compare the postprandial glucodynamic profile of Humalog ... more This double-blind study was designed to compare the postprandial glucodynamic profile of Humalog Mix75/25, a new premixed insulin analogue containing 75% neutral protamine lispro and 25% insulin lispro with that of human insulin 70/30 (70% neutral protamine Hagedorn insulin and 30% regular human insulin) in patients with type 2 diabetes mellitus. Insulin lispro Mix75/25 (Mix75/25) is the first available insulin formulation in which both the rapid-acting and basal components are insulin analogues. This randomized, multicenter, double-blind, crossover study monitored patients&#39; postprandial glucodynamic response to Mix75/25 and human insulin 70/30 (70/30) after a standard test meal. Eighty-four patients with type 2 diabetes participated in this study and were randomly assigned to 1 of 2 treatment sequence groups. Patients received an identical test meal on 4 occasions, completing 2 test meals for each treatment. Equal doses of Mix75/25 or 70/30 were administered 5 minutes before each of the 2 test meals, with doses individualized for each patient. Blood samples were collected for 4 hours after the meal for measurement of plasma glucose. From these plasma glucose measurements, fasting plasma glucose, 2-hour postprandial glucose (2pp), 2-hour postprandial glucose excursion (2pp(ex)), maximum glucose excursion (Gex(max)), the area under the glucose concentration versus time curve from 0 to 4 hours (AUC4), and the area under the glucose excursion versus time curve from 0 to 4 hours (AUCex4) were calculated. Because of significant differences in the baseline fasting plasma glucose levels between Mix75/25 and 70/30 (Mix75/25: 8.9+/-2.2 mmol/L [160.2+/-39.6 mg/dL]; 70/30: 8.6+/-1.9 mmol/L [154+/-34 mg/dL), analyses of the excursion parameters provide a truer comparison of the glucodynamic response between insulin formulations. Mix75/25 resulted in significantly lower values for 2pp(ex) (3.35+/-2.28 vs 4.13+/-2.26 mmol/L), Gex(max) (4.51+/-1.88 vs 5.19+/-1.98 mmol/L), and AUCex4 (8.01+/-7.02 vs 10.6+/-6.47 mmol x h/L) compared with 70/30. In patients with type 2 diabetes mellitus, premeal injection of Mix75/25 resulted in better postprandial glycemic control than did premeal injection of 70/30 in the 4 hours after a standard meal. Mix75/25 is a valuable option for managing postprandial blood glucose in patients with type 2 diabetes mellitus who require insulin.

Research paper thumbnail of Prandial Premixed Insulin Analogue Regimens Versus Basal Insulin Analogue Regimens in the Management of Type 2 Diabetes: An Evidence-Based Comparison

Clinical Therapeutics, 2007

Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which ins... more Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which insulin deficiency is one of the core defects. When patients with T2D are unable to achieve glycemic goals with diet and oral antihyperglycemic medications, a common starting insulin regimen consists of basal or premixed insulin added to oral antihyperglycemic medications. When glycemic goals are not achieved with the initial insulin regimen, a basal-bolus regimen is necessary. This article reviews clinical-trial data on the efficacy and safety profile of prandial premixed insulin analogues (insulin aspart and insulin lispro) compared with basal insulin analogues (insulin glargine, insulin detemir, and insulin lispro protamine suspension), with or without a prandial insulin analogue, in the management of T2D. A systematic search of Ovid, MEDLINE, and EMBASE (1995-2007) was performed to identify published randomized controlled trials comparing prandial premixed insulin analogues with basal insulin analogues, with or without prandial insulin, in patients with T2D. The search terms were premixed insulin analogues, premixed insulin, biphasic insulin aspart, insulin aspart 70/30, insulin aspart 50/50, premixed insulin lispro, insulin lispro 75/25, insulin lispro 50/50, glargine, and detemir. Abstracts presented at the 2005 and 2006 meetings of the American Diabetes Association and the European Association for the Study of Diabetes and bibliographies of the identified studies were also reviewed. Predetermined criteria for study inclusion were treatment duration of at least 12 weeks, T2D diagnosed using valid criteria, use of a basal insulin analogue (with or without rapid-acting insulin) as a study comparator, and use of well-accepted end points (eg, glycosylated hemoglobin [HbA1c], hypoglycemia, preprandial and postprandial blood glucose). Of the identified randomized controlled trials, 3 studies compared premixed insulin analogues containing 70% or 75% basal and 30% or 25% rapid-acting insulin analogue with basal insulin analogues only, and 3 studies evaluated premixed insulin analogues containing 50% basal and 50% rapid-acting insulin analogue with basal insulin analogues only. Use of prandial premixed insulin analogues was associated with better overall and postprandial glycemic control. In the studies that compared twice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA1c ranged from -1.00% to -2.79% and from -0.42% to -2.36%, respectively (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). In the studies that compared thrice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA1c ranged from -0.72% to -1.2% and from -0.3% to -0.75%, respectively (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). These results were achieved with some increase in overall hypoglycemia, but not in nocturnal or severe hypoglycemia. Doses of the premixed insulin analogues were adjusted during the titration period to achieve glycemic goals. The results of this systematic review suggest that regimens consisting of prandial premixed insulin analogues, which provide both basal and prandial insulin coverage, may be used as an initial insulin regimen in patients with T2D to enable better overall, preprandial, and postprandial glycemic control compared with a basal insulin analogue regimen alone. Premixed insulin analogues are an effective option for initiating and intensifying insulin therapy in patients with T2D.

Research paper thumbnail of Effect of exenatide on heart rate and blood pressure in subjects with type 2 diabetes mellitus: a double-blind, placebo-controlled, randomized pilot study

Cardiovascular Diabetology, 2010

Background: Cardiovascular effects of glucose-lowering agents are of increasing interest. Our aim... more Background: Cardiovascular effects of glucose-lowering agents are of increasing interest. Our aim was to assess the effects of the glucagon-like peptide-1 receptor agonist exenatide on heart rate (HR) and blood pressure (BP) in subjects with type 2 diabetes mellitus (T2DM). Methods: In this double-blind, placebo-controlled trial, subjects with T2DM on metformin and/or a thiazolidinedione were randomized to receive exenatide (5 μg for 4 weeks followed by 10 μg) or placebo BID for 12 weeks. Heart rate and BP were assessed with 24-hour ambulatory BP monitoring. The primary measure was change from baseline in mean 24-hour HR.

Research paper thumbnail of A comparison of insulin lispro Mix25™ and human insulin 30/70 in the treatment of type 2 diabetes during Ramadan

Diabetes Research and Clinical Practice, 2003

To compare insulin lispro Mix25 and human insulin 30/70 with regard to their effect on morning an... more To compare insulin lispro Mix25 and human insulin 30/70 with regard to their effect on morning and evening postprandial glucose (PPG) control, and on average daily blood-glucose (BG), in patients with Type 2 diabetes who wish to fast during Ramadan. Insulin lispro Mix25 and human insulin 30/70 were compared in an open-label, multicenter, randomised, crossover study involving 151 patients. Each treatment period had a duration of 14 days during which the patients self-monitored their BG before and 2 h after the main meals on any 3 days within the last 5 days of each treatment period. The 2 h PPG excursion following the main evening meal after sunset was significantly lower with insulin lispro Mix25 (3.4+/-2.9 mmol/l) compared with human insulin 30/70 (4.0+/-3.2 mmol/l, P=0.007). The evening pre-meal fasting BG values were also lower with insulin lispro Mix25 (7.1+/-2.2 mmol/l) versus human insulin 30/70 (7.5+/-2.6 mmol/l, P=0.034). The average daily BG concentration was 9.5+/-2.4 mmol/l during treatment with insulin lispro Mix25 versus 10.1+/-2.5 mmol/l with human insulin 30/70 given in identical doses (P=0.004). When compared with human insulin 30/70, treatment of insulin-requiring Type 2 patients with insulin lispro Mix25 during Ramadan resulted in better average daily glycaemia, and better BG control before and after the evening meal. Insulin lispro Mix25 should be considered as a therapeutic option during Ramadan.