Dennis Kim, MD, Amylin Pharmaceuticals, Inc., 9360 Towne Centre Drive, Suite 110, San Diego, CA 92121, USA. E-mail: email@example.com
Aim: Exenatide, an incretin mimetic for the adjunct treatment of type 2 diabetes (DM2), reduced A1C and weight in 30-week placebo-controlled trials. This analysis examined the effects of exenatide on glycaemic control and weight over an 82-week period in patients with DM2 unable to achieve adequate glycaemic control with sulphonylurea (SU) and/or metformin (MET).
Methods: This interim analysis is of 314 patients who received exenatide in the 30-week placebo-controlled trials and subsequently in 52 weeks of open-label uncontrolled extension studies for 82 weeks of exenatide in total. Patients continued their SU and/or MET regimens throughout.
Results: Patients completed 82 weeks of exenatide treatment [n = 314, 63% M, age 56 ± 10 years, weight 99 ± 21 kg, body mass index 34 ± 6 kg/m2, A1C 8.3 ± 1.0% (mean ± SD)]. Reduction in A1C from baseline to week 30 [−0.9 ± 0.1% (mean ± SE)] was sustained to week 82 (−1.1 ± 0.1%), with 48% of patients achieving A1C ≤ 7% at week 82. At week 30, exenatide reduced body weight (a secondary endpoint) from baseline (−2.1 ± 0.2 kg), with progressive reduction at week 82 (−4.4 ± 0.3 kg). Similar results were observed for the intent-to-treat population (n = 551), with reductions in A1C and weight at week 82 of −0.8 ± 0.1% and −3.5 ± 0.2 kg respectively. The 82-week completer cohort showed statistically significant improvement in some cardiovascular risk factors. The most frequent adverse events were generally mild-to-moderate nausea and hypoglycaemia.
Conclusion: In summary, 82 weeks of adjunctive exenatide treatment in patients with DM2 treated with SU and/or MET resulted in sustained reduction in A1C and progressive reduction in weight, as well as improvement in some cardiovascular risk factors.
It is well-documented that obesity increases the risk for diabetes between 10- and 90-fold, with a 9% increase in risk for every 1 kg increase in weight [1–4]. As the prevalence of obesity has doubled over the past 30 years [2,3], the prevalence of diabetes has also increased, with no reversal of this trend in sight [4,5]. Likewise, weight loss can improve glucose control, as it has been associated with reduction in A1C, improvements in dyslipidemia and hypertension, and reduced mortality [2,6]. However, many current therapies for diabetes, such as insulin, sulphonylureas (SUs) and thiazolidinediones, result in weight gain, an estimated 2 kg for every 1% decrease in A1C [7–9]. In addition, many therapies are associated with hypoglycaemia and oedema and, for some therapies, the likelihood of eventual loss of glycaemic control despite treatment [8,10]. The drawbacks associated with current therapies have led to the development of new antidiabetic therapies.
Described herein are the effects of one such new therapy, exenatide, on glycaemic control, weight and selected cardiovascular risk factors over an 82-week period in patients with type 2 diabetes (DM2) failing maximally effective doses of a SU and/or metformin (MET). Exenatide is the synthetic version of exendin-4, a naturally occurring 39-amino acid peptide that shares several glucoregulatory actions with the mammalian incretin hormone glucagon-like peptide-1 (GLP-1). These actions include glucose-dependent enhancement of insulin secretion [11–16], glucose-dependent suppression of inappropriately high postprandial glucagon secretion [12,15,16] and slowing of gastric emptying [12,15,16] (which may be paradoxically accelerated in people with diabetes ). In addition, exenatide and GLP-1 have been reported to promote β-cell proliferation and neogenesis from precursor cells in vitro, and in vivo in animal models, transforming non-insulin-producing cells into insulin secretory cells [18–20]. Data in animal models and clinical trials also indicate that exenatide reduces food intake and is associated with weight reduction [11,16,21–23].
In three, 30-week, placebo-controlled trials in patients with DM2, treatment with 10 µg exenatide twice daily (BID) resulted in a mean A1C reduction of approximately 1%, with 40% of patients with baseline A1C > 7% achieving A1C measurements of 7% or less [24–26]. On average, patients on the highest dose of exenatide (10 µg BID) also had a statistically significant mean reduction in body weight of approximately 2 kg at 30 weeks [24–26]. The most common adverse event was mild-to-moderate nausea, which decreased over time. The present analysis found that the use of exenatide in patients with DM2 on a background of MET and/or SU over 82 weeks was generally well-tolerated and associated with sustained improvement in A1C, progressive reduction in body weight and improvement in some cardiovascular risk factors.
Main inclusion criteria for all three initial placebo-controlled trials were age between 16 and 75 years and DM2 treated for at least 3 months prior to screening with the maximally effective dose of an SU [27–29], or ≥1500 mg/day of MET, or a combination of these doses of SU and MET. Additional criteria were an A1C between 7.1 and 11.0%, fasting plasma glucose (FPG) concentration <13.3 mmol/L and body mass index (BMI) of 27–45 kg/m2. In addition, patients had no clinically significant (for a DM2 population) abnormal laboratory tests. Female patients were postmenopausal or surgically sterile or using contraceptives for at least 3 months prior to screening and continuing throughout the study. Exclusion criteria included the following: use of thiazolidinediones, meglitinides, α-glucosidase inhibitors, insulin or weight loss drugs within the prior 3 months, use of corticosteroids, drugs known to affect gastrointestinal motility or any investigational drug; evidence of clinically significant comorbid conditions and history of transplantation. To enroll in the respective open-label uncontrolled extension studies, patients had to complete the antecedent 30-week placebo-controlled trial. Furthermore, the patients included in this analysis were randomized to 5 or 10 µg exenatide BID in the placebo-controlled trials and had the chance to complete 82 weeks of exenatide treatment by the time of this analysis. Those patients who had been randomized to placebo in the initial trials were not included in this analysis.
A common clinical protocol was approved for each site by an Institutional Review Board and in accordance with the principles described in the Declaration of Helsinki, including all amendments through the 1996 South Africa revision . All patients provided written informed consent prior to participation.
The initial studies were stratified, balanced, randomized, double-blind, placebo-controlled, parallel-group clinical studies designed to evaluate glycaemic control, as assessed by A1C, and safety in patients with DM2. In one study, patients had been treated with the maximally effective doses of an SU; in a second study, patients had been treated with the maximally effective MET doses (≥1500 mg/day), while in a third study, patients were treated with a combination of maximally effective doses of SU plus MET. SU regimens were described in further detail in published accounts of the 30-week trials [25,26]. Patients were randomized to receive placebo or 5 or 10 µg exenatide subcutaneously (SC) BID in the double-blind 30-week studies. Patients who completed the 30-week studies could continue in open-label extension studies, in which all patients received 5 µg exenatide BID for 4 weeks followed by 10 µg exenatide BID thereafter. Study medication was self-injected SC into the abdomen within 15 min before meals in the morning and evening. Patients continued their MET regimens throughout the studies. The study protocol for the open-label extension studies did not contain guidelines regarding adjustment of SU dosage, therefore any SU dosage adjustment was at the investigator's discretion.
In the open-label extension studies, the primary objectives were to evaluate safety and the changes from baseline to each visit for A1C. A secondary objective was to evaluate changes from baseline to each visit for weight and FPG concentrations. Weight, A1C and FPG analyses were performed for the 82-week completer cohort. This 82-week completer cohort was defined as those patients who received exenatide in the placebo-controlled trials and who completed an additional 52 weeks in the open-label extension studies. Also evaluated were changes in A1C stratified by baseline A1C. Changes in body weight were stratified by baseline BMI and characterized by weight-change quartiles and concomitant antidiabetic medication. Additionally, changes in lipids were determined as a secondary endpoint. Plasma analytes and A1C concentrations were measured as previously described [24–26].
Safety endpoints included adverse events occurring upon or after receiving the first exenatide dose during the placebo-controlled trials through the 82-week period, as well as clinical laboratory tests, physical examination, 12-lead ECG and vital signs. All safety analyses were performed using the 82-week intent-to-treat (ITT) population, defined as all patients who received at least one injection of exenatide in the open-label extension studies and who enrolled with timing such that they could achieve 82 weeks of exenatide treatment prior to the analysis cut-off date. The intensity of hypoglycaemic episodes was defined as mild, moderate or severe. For mild or moderate hypoglycaemia, patients reported symptoms consistent with hypoglycaemia that may have been documented by a blood glucose concentration value (<60 mg/dl) and did not require the assistance of another person. For severe hypoglycaemia, patients required the assistance of another person to obtain treatment for their hypoglycaemia, such as food, drink, intravenous glucose or intramuscular glucagon.
In addition, A1C and weight analyses were performed for the 82-week ITT population.
The 95% confidence intervals for the changes from baseline (week 0) to endpoints in A1C, body weight and selected cardiovascular risk factors were provided. For the 82-week completer cohort, missing week 82 results were imputed from scheduled or unscheduled postbaseline visits using the last observation carried forward (LOCF) method, and observed data were used for other timepoints. For the 82-week ITT population, missing results at all postbaseline timepoints were imputed from scheduled or unscheduled postbaseline visits using the LOCF method. Additionally, the observed cases method was used for the 82-week ITT population. Results are given as mean ± SE unless otherwise indicated. For weight-change quartile analysis, quartiles consisted of four subgroups with approximately equal number of subjects (n = 78–79) in each subgroup, with quartile 1 consisting of the 25% of subjects with the greatest weight reductions at week 82, quartile 4 consisting of the 25% of subjects with the smallest weight reduction (or weight gain) and quartiles 2 and 3 are for those with the intermediate weight changes.
A1C and body weight were evaluated for different nausea subgroups to determine what effect nausea may have had on these variables. Patients were categorized based on whether they reported nausea during weeks 0–8 and whether it occurred for more than 7 days during weeks 8–82. Specifically, those patients who did not have nausea in the first period and had nausea for 7 or less days in the second period were in the ‘none’ subgroup. The ‘early’ subgroup consisted of patients who had nausea during weeks 0–8 and nausea during 7 or less days in weeks 8–82. The ‘sustained’ subgroup consisted of patients who had nausea during weeks 0–8 and nausea during more than 7 days in weeks 8–82. The ‘late’ subgroup consisted of patients who did not have nausea during weeks 0–8 but reported nausea during more than 7 days in weeks 8–82 (table 3). Descriptive statistics were provided for these subgroups for changes in A1C and weight. Additional information on statistical methods can be found in the publications of the placebo-controlled trials [24–26].
Table 3. A1C and weight change by nausea subgroup (82-week completer cohort n = 314)
Change in A1C (%)
Change in weight (kg)
Study Design, Patient Demographics and Disposition
The original 30-week placebo-controlled trials were of 1446 patients randomized to three arms (placebo, 5 and 10 µg exenatide BID). During the 30 weeks of the placebo-controlled trials, 22% of these patients withdrew, primarily due to withdrawal of consent (6.5%), adverse event (5.9%) and loss of glucose control (4.1%). Amongst the patients who withdrew due to an adverse event, 27 (1.9% of the total population) withdrew due to nausea and 1 (< 0.1%) withdrew due to hypoglycaemia. Of the 1125 patients who completed the placebo-controlled trials, 974 (87%) chose to enter the open-label extension studies. During these extension studies, all patients received 5 µg exenatide BID for 4 weeks followed by 10 µg exenatide BID thereafter.
Of the original eligible cohort for the open-label extension studies (those on active drug during the initial study and for whom 82 weeks of follow-up was possible for this interim analysis, dashed box on figure 1a), also designated the 82-week ITT population (n = 551), 314 (57%) completed 82 weeks of exenatide treatment (82-week completer cohort). The most common reasons for withdrawal during the 52 weeks of the open-label extension studies were withdrawal of consent (11%), adverse event (7%) and administrative (10%). Amongst the patients who withdrew due to an adverse event, 20 (3.6% of the 82-week ITT population) withdrew due to nausea and 2 (0.4%) withdrew due to hypoglycaemia. Administrative withdrawals were largely due to the closure of study sites, which took place over a period of weeks.
Demographic characteristics of the 82-week completer cohort are similar to the 82-week ITT population (table 1), as well as those patients randomized in the original placebo-controlled trials [24–26].
Table 1. Patient disposition and baseline demographics for 82-week clinical trials [82-week intent-to-treat (ITT) population, n = 551, and 82-week completer cohort, n = 314]
Data are mean ± SD unless otherwise indicated. Percentages may add up to less or more than 100 due to rounding.
Other includes lost to follow-up, investigator decision, protocol violation and administrative (which includes those patients who were unable to continue because their study sites closed).
In the 82-week completer cohort (which included patients receiving 5 or 10 µg exenatide BID for the first 30 weeks), a decrease in A1C was seen in the first 30 weeks of exenatide treatment, with a change from baseline of −0.9 ± 0.1% (figure 2a), comparable with the changes of −0.8 to −0.9% with the 10 µg BID dose (vs. 0.1 to 0.2% for placebo) in the 30-week placebo-controlled clinical trials [24–26]. The reduction in A1C was maintained, with a change from baseline of−1.1 ± 0.1% (95% CI: −1.0 to −1.3%) at week 82. The proportion of patients with baseline A1C > 7% (n = 289) who achieved an A1C ≤ 7% were 39 and 48% at weeks 30 and 82 respectively (figure 2b). When patients were stratified by baseline A1C, greater changes in A1C were observed for the group with baseline A1C ≥ 9% (−2.0 ± 0.2%) compared with those with baseline A1C < 9% (−0.8 ± 0.1%) at week 82, with similar findings for week 30 (figure 2c).
To determine whether bias was introduced by patient withdrawal from the study, we also determined A1C changes for the 82-week ITT population (using the LOCF method). With this approach, the 82-week ITT population (LOCF) had sustained A1C changes from baseline of −0.8 ± 0.1% (95% CI: −0.6 to −0.9%) at week 82 (figure 2a). When a similar analysis was performed for the 82-week ITT population using the observed cases method, the A1C changes were intermediate between the 82-week completer and 82-week ITT population (LOCF) (data not shown). That the reductions and pattern of reductions were similar for all three data sets indicates that most of those who withdrew from the study did so for reasons unrelated to efficacy.
For the 82-week completer cohort, FPG values declined during the 30 weeks of the placebo-controlled trials, with a change from baseline of −0.7 ± 0.1 mmol/l, which was maintained out to week 82 when the change from baseline was −0.9 ± 0.2 mmol/l.
At week 30, the change in body weight from baseline for the 82-week completer cohort was −2.1 ± 0.2 kg (figure 3a) comparable with the changes of −1.6 to−2.8 kg with the 10 µg BID dose (vs. −0.3 to −0.9 kg for placebo) in the 30-week placebo-controlled clinical trials [24–26]. Reduction in body weight was progressive, with a change from baseline of −4.4 ± 0.3 kg (95% CI: −3.8 to −5.1 kg) at week 82 or 4.4% of baseline body weight. At week 82, 81% of patients had lost weight. When weight changes were examined by weight-change quartile (with patients in quartile 1 losing the most weight, and those in quartile 4 losing the least, or gaining, weight), patients in quartile 1 lost an average of 11.9 kg (11.4% of baseline body weight), with smaller reductions in quartiles 2 and 3, and a mean weight gain of 1.7 kg (1.8% of baseline body weight) for quartile 4 (figure 3b). Patients in all four weight-change quartiles had reductions in A1C from baseline ranging from 1.7% for quartile 1 to 0.7% for quartile 4 (figure 3c). Baseline BMI affected the magnitude of the weight reduction: those patients with baseline BMI < 25 had a mean weight reduction of 2 kg (2.9% of baseline body weight), whereas those with baseline BMI ≥ 40 had a mean reduction of over 7 kg (5.5% of baseline body weight) (figure 3d). Lastly, weight reduction was examined by concomitant antidiabetic medication. Those patients taking only MET along with exenatide had a mean weight reduction of 5.3 kg (5.2% of baseline body weight) compared with 3.9 kg for exenatide plus an SU (4.0% baseline body weight) and 4.1 kg for exenatide plus an SU and MET (4.1% baseline body weight) (figure 3e).
To assess for potential bias introduced by patient withdrawal from the study, we again used the conservative approach of determining reduction in body weight in the 82-week ITT population (using LOCF). The 82-week ITT (LOCF) population had weight changes from baseline of −3.5 ± 0.2 kg (95% CI: −3.1 to −4.0 kg) at week 82 (figure 3a). As with the 82-week completer cohort, reduction in body weight was progressive for the 82-week ITT population. Again, intermediate results were obtained for the 82-week ITT population when the observed cases method was used (data not shown).
Clinical Laboratory Findings and Safety
Exenatide treatment was generally well tolerated. There were no adverse trends in vital sign measurements or patterns of abnormal findings on physical examination. The most frequent adverse events were nausea and hypoglycaemia (table 2), which were generally mild to moderate in intensity, and accounted for withdrawal rates of 3.6 and 0.4% respectively. Hypoglycaemic episodes were almost exclusively mild to moderate in intensity, with four cases of severe hypoglycaemia requiring assistance from another person. All of these episodes occurred in the context of concomitant SU therapy. In one instance, assistance by medical personnel was provided; the patient walked into the hospital, received intravenous dextrose 50% and reported feeling better after 20 min.
Table 2. Most frequent adverse events with an overall incidence ≥ 10% by 10-week intervals [82-week intent-to-treat (ITT) population, n = 551]
Placebo-controlled trials (weeks 0–30)
Open-label uncontrolled extension (weeks 30-82)
To examine whether reduction in body weight was associated with nausea, the incidence of nausea over time was analysed and compared to the reduction in body weight. The incidence of nausea was highest during the initial weeks of dosing (weeks 0–4). Nausea also occurred more frequently during the first 8 weeks of the open-label extension studies (weeks 30–38), when all patients received 5 µg exenatide BID for 4 weeks, before increasing to 10 µg exenatide BID. Other than those 2-time periods, the incidence of nausea remained stable (data not shown). While the incidence of nausea remained stable, body weight reduction was progressive (figure 3). To further examine this issue, patients were grouped into categories based on the extent of nausea reported during weeks 0–8 and 8–82 (table 3). Patients experiencing varying amounts of nausea had similar changes in A1C and weight. Pearson correlation analysis that examined the nausea-by-weight correlations in the 82-week completer cohort found that the reduction in body weight was unlikely to be driven by the direct effect of nausea (r = −0.11).
Selected parameters were assessed for the 82-week completer cohort as a secondary endpoint. Statistically significant changes were observed for high-density lipoprotein cholesterol (HDL-C) concentrations (0.12 mmol/l), triglyceride concentrations (−0.43 mmol/l) and sitting diastolic blood pressure (−2.7 mmHg) (table 4). Other parameters examined (total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and systolic blood pressure) also showed trends towards improvement, although they did not achieve statistical significance. The cardiovascular risk factors were also assessed by weight-change quartile. In those patients with the greatest weight reductions, even greater beneficial changes were observed for blood pressure [−3.9 mmHg (systolic) and −4.4 mmHg (diastolic)] and lipid profiles, with changes of 0.19 mmol/l for HDL-C and −1.04 mmol/l for triglycerides (figure 4).
Table 4. Change from baseline for lipids and sitting blood pressure (82-week completer cohort n = 314)
In this interim analysis of 314 patients treated for 82 weeks with exenatide, we observed sustained improvement in glycaemic control, progressive reduction in body weight and improvement in some cardiovascular risk factors in patients with DM2 who were unable to achieve glycaemic control with maximally effective doses of an SU, MET or both. This current analysis adds to prior published data with exenatide by inclusion of a much longer period of clinical follow-up on active drug therapy. Several shortcomings of a long-term observational study such as this must be considered, including the absence of a comparator group, the changing nature of the study and the selection of a small subset of subjects. After week 30, the trial changed from being double-blind placebo-controlled to open-label, with roughly half of the patients experiencing an increase in dose (from 5 to 10 µg exenatide BID). These changes may account for the notable fall in both body weight and A1C observed after the transition to the open-label extension studies. Another consideration is that this analysis is of the 314 patients who comprise the 82-week completer cohort compared with the 1446 patients who entered the placebo-controlled trials. As depicted in figure 1, there are several reasons why the 82-week completer cohort is only a fraction of those who started the trials, including attrition, exclusion of patients randomized to placebo and exclusion of those patients who did not have the opportunity to complete 82 weeks of exposure. This approach was selected, as the current analysis measures the clinical effects of ongoing exenatide treatment in patients appropriate for long-term exenatide therapy. Thus, we compare the 82-week completer cohort (n = 314) to the subset of patients who had the opportunity to receive 82 weeks of exenatide exposure (82-week ITT population, n = 551). To address the possibility of self-selection, we examined A1C and weight effects for the 82-week ITT population, using both the LOCF and the observed cases methods. Both A1C and weight changes were similar to those observed in the 82-week completer cohort, although smaller in magnitude. As these data argue against any sizeable role for self-selection bias, we believe that the benefits from exenatide treatment described here are representative of what most patients would experience with long-term exenatide therapy in a real-world clinical setting.
Unlike some other antidiabetic medications, which are associated with weight gain , exenatide treatment was associated with progressive reduction in body weight, with 81% of patients losing weight. This reduction in body weight was especially notable, as no specific diet or exercise counselling or caloric restriction was required by the study. There was no apparent plateau for the weight reduction by week 82. Ongoing studies of patients who received exenatide for even longer time periods will demonstrate whether reduction in body weight continues.
One concern is whether nausea could account for the observed weight reduction. Three lines of evidence indicate that nausea is not a major cause of the weight reduction with exenatide. First, while the incidence of nausea was highest during treatment initiation and dose escalation, decreasing after those time periods, weight reduction was progressive over 82 weeks. Second, weight reduction was observed for patients with varying amounts of nausea, including the majority of patients (54%) who had no or minimal nausea (table 3). Third, Pearson correlation analysis found that the reduction in body weight was unlikely to be driven by the direct effect of nausea (r = −0.11). The progressive reduction in body weight is probably primarily due to exenatide's actions of inducing satiety and reducing food intake, independent of any gastrointestinal side effects .
Exenatide treatment was also associated with significant improvement in some cardiovascular risk factors: HDL-C, triglycerides and diastolic blood pressure. The greatest improvement in cardiovascular risk factors was seen with those patients who had the greatest reductions in weight. The lipid changes seen with exenatide are notable as the improvement in lipid profiles occurred even in the absence of profound weight loss and across a range of changes in A1C. These trends toward improvement in cardiovascular risk factors are of particular interest given the 2–4 fold increased risk of cardiovascular disease in individuals with diabetes . Whether the changes in cardiovascular risk factors seen with exenatide treatment would have a substantial impact on future cardiovascular outcomes is not known.
In the 82 weeks of follow-up, exenatide was generally well-tolerated, with mild-to-moderate nausea and hypoglycaemia the most common adverse events. The increase in nausea seen during weeks 30–38 may be in part due to unblinding, as patient expectation may affect nausea reporting. Additionally, those patients who had been randomized to 5 µg exenatide BID during the placebo-controlled trials were escalated to 10 µg exenatide BID.
Exenatide represents a novel therapy based on the glucoregulatory actions of GLP-1. As such, this compound may offer a unique treatment option, leveraging a number of metabolic benefits, when oral therapies can no longer achieve adequate glycaemic control. The demonstration of these findings in an observational, long-term report suggests that exenatide therapy possesses an excellent and stable long-term glucose lowering effect, in association with a significant reduction in body weight and improvement in some cardiovascular risk factors. These effects were observed in individuals with DM2 receiving long-term exenatide therapy who were unable to maintain adequate glycaemic control using the well described and widely accepted approaches of MET, SU or combined MET-SU therapy.
The authors thank the exenatide-112, exenatide-112E, exenatide-113, exenatide-113E, exenatide-115 and exenatide-115E Clinical Study Groups for their excellent assistance in the conduct, reporting, and quality control of the studies, and all the patients who volunteered to participate. All authors analysed the data reported here, and all authors contributed to and reviewed the final manuscript. The following are gratefully acknowledged for their valuable contributions to the conduct, reporting and quality control of the study and to the development of the manuscript: Maria Aisporna, Tom Bicsak, Erich Blase, Brian Dangel, Berg Deridian, Mark Fineman, Eling Gaines, Xuesong Guan, Jennifer Johnson, Szecho Lin, June Mendoza, Amanda Montoya-Varns, Loretta Nielsen, James Ruggles, Eric Schoenamsgruber, Cinde Scroggins, Larry Shen, Carrie Shi, Georgia Tsaroucha, Trish Tsay, Matthew Wintle, Liping Xie and Dongliang Zhuang. Supported by Amylin Pharmaceuticals Inc, San Diego, CA 92121, and Eli Lilly and Company, Indianapolis, IN 46285.
Principal investigators in the exenatide 2993-112E, 2993-113E and 2993-115E clinical studies were Abbott L, Abernethy J, Ahmann A, Albery R, Albu J, Allam R, Arakaki R, Argoud G, Baron M, Berwald B, Black J, Blonde L, Bock A, Buse J, Busick E, Canadas R, Casner P, Cathcart H, Cavanaugh J, Chaykin L, Cherlin R, Chertman M, Chithranjan N, Cohen AJ, Cohen J, Cohen L, Collins G, Conway M, Corder C, Corn L, Cyrus J, de la Garza C, DeFronzo R, Doty T, Duckor S, Durden J, Eliosoff R, Farnsworth K, Farooqi M, Farrell J, Fernandes J, Fishman N, Fogelfeld L, Forker A, Freedman L, Gaman W, Garg S, Garvey W, Gavin L, Geary B, Gee D, Gilbert J, Gupta A, Harrison B, Hartman I, Harvey W, Herring C, Heuer M, Holloway R, Horowitz B, Isley W, James D, Kaplan R, Kawley A, Kayne D, Kendall D, Kim K, Klein E, Klonoff D, Knecht T, Kopin L, LaCava E, Leichter S, Levinson L, Littlejohn T, Magee M, Magill S, Martinez D, McInroy R, Mendelson A, Miller J, Miller S, Mills R, Moretto T, Moriarity P, Mudaliar S, Myers L, Nath C, Norwood P, Olansky L, Osei K, Philis-Tsimikas A, Pullman J, Raad G, Radparvar A, Reith P, Riff D, Rigby S, Robinson J, Rood R, Rosenstock P, Saponaro J, Schachtman B, Schumacher D, Schwartz S, Shapiro J, Shapiro W, Sherman L, Shockey G, Silver G, Smith W, Snyder J, Sugimoto D, Sullivan J, Taber L, Troupin B, Tuttle L, Ward W, Weerasinghe M, Weinstein R, Weiss D, Weiss R, Weissman P, Whitehouse F, Williams K, Winer N, Wofford M, Wright D, Wysham C, Yates S, Zayed A, Zemel L, Zigrang W.