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Dive into the research topics where Alan G. Zimmermann is active.

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Featured researches published by Alan G. Zimmermann.


Diabetes Care | 2015

Efficacy and Safety of Once-Weekly Dulaglutide Versus Insulin Glargine in Patients With Type 2 Diabetes on Metformin and Glimepiride (AWARD-2)

Francesco Giorgino; Marian Benroubi; Jui-Hung Sun; Alan G. Zimmermann; Valeria Pechtner

OBJECTIVE This study compared the efficacy and safety of once-weekly dulaglutide, a glucagon-like peptide-1 receptor agonist, with daily insulin glargine, both combined with maximally tolerated doses of metformin and glimepiride in patients with type 2 diabetes. The primary objective was noninferiority of dulaglutide 1.5 mg to glargine in the HbA1c change from baseline at 52 weeks. RESEARCH DESIGN AND METHODS In this 78-week, open-label study, 810 patients were randomized to dulaglutide 1.5 mg, dulaglutide 0.75 mg, or glargine. RESULTS The baseline mean ± SD HbA1c was 8.1 ± 1.0% (65.5 ± 10.8 mmol/mol). The least squares mean ± SE HbA1c change from baseline to the primary end point was −1.08 ± 0.06% (−11.8 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, −0.76 ± 0.06% (−8.3 ± 0.7 mmol/mol) for dulaglutide 0.75 mg, and −0.63 ± 0.06% (−6.9 ± 0.7 mmol/mol) for glargine, with an end point mean ± SD dose of 29 ± 26 units (0.33 ± 0.24 units/kg), and a fasting plasma glucose (mean ± SD) of 118 ± 23 mg/dL from self-monitored plasma glucose. Statistical criteria for superiority were met with dulaglutide 1.5 mg and for noninferiority with dulaglutide 0.75 mg. More patients on dulaglutide 1.5 mg achieved HbA1c targets <7.0% (53 mmol/mol) versus glargine (P < 0.001). Body weight decreased with dulaglutide and increased with glargine. Total hypoglycemia rates were lower with dulaglutide; severe hypoglycemia was minimal. Increases in pancreatic enzymes were observed for dulaglutide. Incidence of nausea (15.4, 7.7, and 1.5%) and diarrhea (10.6, 9.2, and 5.7%) were more common with dulaglutide 1.5 mg and 0.75 mg than with glargine. CONCLUSIONS Once-weekly dulaglutide 1.5 mg, compared with daily insulin glargine without forced titration, demonstrated greater HbA1c reduction and weight loss, with a higher incidence of gastrointestinal adverse events and a lower risk of hypoglycemia.


The Journal of Clinical Endocrinology and Metabolism | 2010

Prevalence of metabolic syndrome in adult hypopituitary growth hormone (GH)-deficient patients before and after GH replacement.

Andrea F. Attanasio; Daojun Mo; Eva Marie Erfurth; Meng Tan; Ken Y. Ho; David L. Kleinberg; Alan G. Zimmermann; Philippe Chanson

CONTEXT AND OBJECTIVE Metabolic and body compositional consequences of GH deficiency (GHD) in adults are associated with a phenotype similar to the metabolic syndrome (MetS). PATIENTS We assessed MetS prevalence in adult GHD patients (n = 2531) enrolled in the Hypopituitary Control and Complications Study. Prevalence was assessed at baseline and after 3 yr of GH replacement in a subset of 346 adult-onset patients. RESULTS Baseline MetS crude prevalence was 42.3%; age-adjusted prevalence in the United States and Europe was 51.8 and 28.6% (P < 0.001), respectively. In the United States, age-adjusted prevalence was significantly higher (P < 0.001) than in a general population survey. Increased MetS risk at baseline was observed for age 40 yr or older (adjusted relative risk 1.34, 95% confidence interval 1.17-1.53, P < 0.001), females (1.15, 1.05-1.25, P = 0.002), and adult onset (1.77, 1.44-2.18, P < 0.001). In GH-treated adult-onset patients, MetS prevalence was not changed after 3 yr (42.5-45.7%, P = 0.172), but significant changes were seen for waist circumference (62.1-56.9%, P = 0.008), fasting glucose (26.0-32.4%, P < 0.001), and blood pressure (59.8-69.7%, P < 0.001). Significantly increased risk of MetS at yr 3 was associated with baseline MetS (adjusted relative risk 4.09, 95% confidence interval 3.02-5.53, P < 0.001) and body mass index 30 kg/m(2) or greater (1.53, 1.17-1.99, P = 0.002) and increased risk (with a P value < 0.1) for GH dose 600 microg/d or greater (1.18, 95% confidence interval 0.98-1.44, P = 0.088). CONCLUSION MetS prevalence in GHD patients was higher than in the general population in the United States and higher in the United States than Europe. Prevalence was unaffected by GH replacement, but baseline MetS status and obesity were strong predictors of MetS after GH treatment.


The Journal of Clinical Endocrinology and Metabolism | 2013

Prospective Safety Surveillance of GH-Deficient Adults: Comparison of GH-Treated vs Untreated Patients.

Mark L. Hartman; Rong Xu; Brenda J. Crowe; Leslie L. Robison; Eva Marie Erfurth; David L. Kleinberg; Alan G. Zimmermann; Whitney W. Woodmansee; Gordon B. Cutler; John J. Chipman; Shlomo Melmed

Context: In clinical practice, the safety profile of GH replacement therapy for GH-deficient adults compared with no replacement therapy is unknown. Objective: The objective of this study was to compare adverse events (AEs) in GH-deficient adults who were GH-treated with those in GH-deficient adults who did not receive GH replacement. Design and Setting: This was a prospective observational study in the setting of US clinical practices. Patients and Outcome Measures: AEs were compared between GH-treated (n = 1988) and untreated (n = 442) GH-deficient adults after adjusting for baseline group differences and controlling the false discovery rate. The standardized mortality ratio was calculated using US mortality rates. Results: After a mean follow-up of 2.3 years, there was no significant difference in rates of death, cancer, intracranial tumor growth or recurrence, diabetes, or cardiovascular events in GH-treated compared with untreated patients. The standardized mortality ratio was not increased in either group. Unexpected AEs (GH-treated vs untreated, P ≤ .05) included insomnia (6.4% vs 2.7%), dyspnea (4.2% vs 2.0%), anxiety (3.4% vs 0.9%), sleep apnea (3.3% vs 0.9%), and decreased libido (2.1% vs 0.2%). Some of these AEs were related to baseline risk factors (including obesity and cardiopulmonary disease), higher GH dose, or concomitant GH side effects. Conclusions: In GH-deficient adults, there was no evidence for a GH treatment effect on death, cancer, intracranial tumor recurrence, diabetes, or cardiovascular events, although the follow-up period was of insufficient duration to be conclusive for these long-term events. The identification of unexpected GH-related AEs reinforces the fact that patient selection and GH dose titration are important to ensure safety of adult GH replacement.


The Journal of Clinical Endocrinology and Metabolism | 2010

Metabolic, Cardiovascular, and Cerebrovascular Outcomes in Growth Hormone-Deficient Subjects with Previous Cushing’s Disease or Non-Functioning Pituitary Adenoma

Susan M. Webb; Daojun Mo; Steven W. J. Lamberts; Shlomo Melmed; Francesco Cavagnini; Francesca Pecori Giraldi; Christian J. Strasburger; Alan G. Zimmermann; Whitney W. Woodmansee

CONTEXT Previous exposure to hypercortisolism due to Cushings disease (CD) may adversely affect long-term metabolic and cardiovascular outcomes. In particular, metabolic and cardiovascular outcomes of patients with previous CD who require GH replacement have not been fully established. OBJECTIVE The aim of the study was to compare the prevalence and incidence of metabolic syndrome (Adult Treatment Panel III criteria), diabetes mellitus, cardiovascular disease, and cerebrovascular disease in GH-treated subjects with previous CD with GH-treated subjects with previous nonfunctioning pituitary adenoma (NFPA). DESIGN We conducted post hoc analysis of the observational Hypopituitary Control and Complications Study conducted at 362 international centers (1995-2006). SUBJECTS We studied adult-onset GH-deficient subjects with previous CD (n = 160) or NFPA (n = 879). All subjects received GH replacement therapy and were GH naive at enrollment. Multiple pituitary deficits were prevalent in both groups. MAIN OUTCOME MEASURES We measured the prevalence and incidence of metabolic syndrome, diabetes mellitus, cardiovascular disease, and cerebrovascular disease at baseline and at 3 yr, standardized for age and sex differences between groups. RESULTS Compared with subjects with previous NFPA, subjects with previous CD had a significantly greater 3-yr incidence of metabolic syndrome (CD, 23.4%; NFPA, 9.2%; P = 0.01), baseline (CD, 6.3%; NFPA, 2.2%; P < 0.01) and 3-yr (CD, 7.6%; NFPA, 3.9%; P = 0.04) prevalence of cardiovascular disease, and baseline (CD, 6.4%; NFPA, 1.8%; P = 0.03) and 3-yr (CD, 10.2%; NFPA, 2.9%; P = 0.01) prevalence of cerebrovascular disease. CONCLUSIONS Previous hypercortisolism may predispose GH-treated, GH-deficient subjects with prior CD to an increased risk of metabolic syndrome, cardiovascular disease, and cerebrovascular disease.


The Journal of Clinical Endocrinology and Metabolism | 2011

Prevalence and Incidence of Diabetes Mellitus in GH-Treated Children and Adolescents: Analysis from the GeNeSIS Observational Research Program

Christopher J. Child; Alan G. Zimmermann; Robin S. Scott; Gordon B. Cutler; Tadej Battelino; Werner F. Blum

BACKGROUND GH has an insulin antagonist effect, and GH treatment has therefore been suggested to impair glucose metabolism and increase risk of diabetes mellitus. SETTING Data from 11,686 GH-treated patients in the Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS), a multinational observational study of children with growth disorders, were analyzed for diabetes incidence. Baseline diabetes prevalence was determined from a GH-naive subgroup. METHODS Prevalence and incidence (by standardized incidence ratio) were compared with results from patients aged less than 20 yr in the U.S. SEARCH for Diabetes in Youth study. RESULTS Baseline type 1 diabetes prevalence per 1000 persons was 4.92 (95% confidence interval = 1.91-12.58) in GeNeSIS and 1.03 (0.97-1.10) in SEARCH for 0- to 9-yr-olds, and 7.33 (4.20-12.77) and 2.99 (2.78-2.98), respectively, for 10- to 19-yr-olds; there were no GeNeSIS cases of type 2 diabetes before GH initiation. During a median 1.8 yr of GH treatment, diabetes standardized incidence ratios for U.S. patients were 1.4 (0.5-3.1) for type 1 and 8.5 (2.8-19.5) for type 2, and for all patients was 1.4 (0.7-2.4) for type 1 and 6.5 (3.3-11.7) for type 2. Among the 11 patients with incident type 2 diabetes, risk factors for diabetes were identified in 10 patients. Glucose concentrations normalized for seven of nine patients for whom glycemic status could be determined (three of whom continued GH therapy and four who discontinued). CONCLUSION The incidence of type 2 diabetes was higher in GH-treated children than the general population. Monitoring of glucose, before and periodically during GH treatment, is recommended for those with preexisting type 2 diabetes risk factors.


The Journal of Clinical Endocrinology and Metabolism | 2013

GH Treatment to Final Height Produces Similar Height Gains in Patients With SHOX Deficiency and Turner Syndrome: Results of a Multicenter Trial

Werner F. Blum; Judith L. Ross; Alan G. Zimmermann; Charmian A. Quigley; Christopher J. Child; G. Kalifa; Cheri Deal; Stenvert L. S. Drop; Gudrun Rappold; Gordon B. Cutler

CONTEXT Growth impairment in short stature homeobox-containing gene (SHOX) deficiency and Turner syndrome share a similar etiology. Because of the established effect of GH treatment on height in patients with Turner syndrome, we hypothesized that GH therapy would also stimulate growth in patients with SHOX deficiency. OBJECTIVE Our objectives were to evaluate long-term efficacy of GH treatment in short patients with SHOX deficiency and to compare the effect on final (adult) height (FH) in patients with SHOX deficiency and Turner syndrome. DESIGN AND SETTING A prospective, multinational, open-label, randomized 3-arm study consisting of a 2-year control period and a subsequent extension period to FH. The treatment groups were 1) SHOX-D-C/GH (untreated during the control period, GH-treated during the extension), 2) SHOX-D-GH/GH, and 3) Turner-GH/GH (GH-treated during both study periods). PATIENTS Short-statured prepubertal patients with genetically confirmed SHOX deficiency (n = 49) or Turner syndrome (n = 24) who participated in the extension. INTERVENTION Depending on the study arm, patients received a daily sc injection of 0.05 mg/kg recombinant human GH from start of the study or start of the extension until attainment of FH or study closure. RESULTS Height SD score gain from start of GH treatment to FH was similar between the combined SHOX-deficient groups (n = 28, 1.34 ± 0.18 [least-squares mean ± SE]) and the Turner group (n = 19, 1.32 ± 0.22). In this FH population, 57% of the patients with SHOX deficiency and 32% of the patients with Turner syndrome achieved a FH greater than -2 SD score. CONCLUSIONS GH treatment in short children with SHOX deficiency showed similar long-term efficacy as seen in girls with Turner syndrome.


European Journal of Endocrinology | 2011

Assessment of primary cancers in GH-treated adult hypopituitary patients: an analysis from the Hypopituitary Control and Complications Study

Christopher J. Child; Alan G. Zimmermann; Whitney W. Woodmansee; Daniel M. Green; Jian J Li; Heike Jung; Eva Marie Erfurth; Leslie L. Robison

Objective GH and IGFs have mitogenic properties, causing speculation that GH treatment could increase risk of malignancy. While studies in GH-treated childhood cancer survivors have suggested a slight increase in second neoplasms, studies in GH-treated adults have been equivocal. Design Incidence of de novo and second cancers was evaluated in 6840 GH-treated and 940 non GH-treated adult patients in the Hypopituitary Control and Complications Study pharmacoepidemiological database. Methods Evident cancer cases were evaluated in the main analysis, with sensitivity analyses including probable and possible cancers. Standardized incidence ratios (SIRs) for cancers were calculated using Surveillance, Epidemiology and End Results for the USA and GLOBOCAN for all other countries. Results During the mean follow-up of 3.7 years/GH-treated patient, 142 evident cancer cases were identified, giving an overall SIR of 0.88 (95% confidence interval (CI) 0.74–1.04); 95% CIs included the value of 1.0 for each country examined. The SIR for GH-treated patients from the USA (71 cases) was 0.94 (95% CI 0.73–1.18), and for non GH-treated patients from the USA (27 cases) was 1.16 (95% CI 0.76–1.69). For GH-treated patients from the USA aged <35 years, the SIR (six cases) was 3.79 (1.39–8.26), with SIR not elevated for all other age categories; SIR for patients from the USA with childhood onset (CO) GH deficiency (GHD) was 2.74 (95% CI 1.18–5.41). The SIR for colorectal cancer in GH-treated patients (11 cases) was 0.60 (95% CI 0.30–1.08). Conclusions With relatively short follow-up, the overall primary cancer risk in 6840 patients receiving GH as adults was not increased. Elevated SIRs were found for subgroups in the USA cohort defined by age <35 years or CO GHD.


Veterinary Parasitology | 2010

Effects of orally administered spinosad (Comfortis) in dogs on adult and immature stages of the cat flea (Ctenocephalides felis).

Byron L. Blagburn; David R. Young; Columba Moran; Jeffery Alan Meyer; Anna Leigh-Heffron; Tandy Paarlberg; Alan G. Zimmermann; Daniel H. Mowrey; Scott Wiseman; Daniel E. Snyder

The efficacy of spinosad against adult fleas (Ctenocephalides felis) on dogs was evaluated in three controlled, blinded studies. One study was conducted to determine speed of kill on experimentally infested dogs. Two additional studies were designed to assess the efficacy of spinosad in preventing environmental contamination with flea eggs (USA study and EU study). An additional objective of the USA study was to assess the effects of skin and hair-coat debris from spinosad-treated dogs on eggs and larvae of C. felis. Dogs were randomly allocated to treatment with beef-flavored spinosad tablets, administered orally at a minimum dosage of 30mg/kg, or placebo. In the first study, speed of kill was determined by flea comb counts performed at 0.5, 1, 2, 4, 8, 12, 24 and 48h after spinosad treatment. Reductions in geometric mean flea counts for spinosad-treated dogs, compared to placebo were 53.7% at 0.5h, 64.2% at 1h, 85.8% at 2h and 100% at 4 through 48h post-treatment (p<0.05 at 1h and beyond). In the 2 flea egg production studies, dogs were treated (spinosad or placebo) once on day 0, infested with 600 fleas approximately 3h post-treatment and reinfested with approximately 600 fleas at intervals over 1 month. Flea eggs were collected starting at approximately 72h after each infestation. Eggs were examined for any effects of spinosad on egg viability. Efficacy of spinosad was also evaluated against environmental eggs and larvae exposed to canine hair-coat debris collected on days 3, 7, 14, 21, and 30. Spinosad was highly effective in reducing flea egg production (>99.8% across the entire study period) compared to control dogs in both egg collection studies. Insufficient numbers of eggs were recovered from spinosad-treated dogs to determine the viability of those eggs. There was no evidence of any effect on environmental flea stages, indicating that spinosad was not present in the skin debris of spinosad-treated dogs. The capability of spinosad to quickly kill adult fleas, and to greatly reduce egg production following challenge with high numbers of adult fleas is important in breaking the flea life cycle and preventing the introduction and establishment of new flea infestations in the household.


European Journal of Endocrinology | 2013

Incidence of second neoplasm in childhood cancer survivors treated with GH: an analysis of GeNeSIS and HypoCCS

Whitney W. Woodmansee; Alan G. Zimmermann; Christopher J. Child; Qi Rong; Eva Marie Erfurth; Paolo Beck-Peccoz; Werner F. Blum; Leslie L Robison

OBJECTIVE Childhood cancer survivors are commonly treated with GH for GH deficiency that develops either as a result of primary malignancy or its treatment. One study--the Childhood Cancer Survivor Study (CCSS)--demonstrated increased risk of second neoplasm (SN) in GH-treated childhood cancer survivors compared with non-GH treated, after adjusting for key risk factors. We assessed the incidence of SN in GH-treated childhood cancer survivors in outpatient observational studies of GH replacement. DESIGN Retrospective analysis of two prospective cohort studies that collected data on safety of GH replacement as prescribed in clinical practice. METHODS Childhood cancer survivors enrolled in Eli Lilly and Companys pediatric (Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS)) and adult (Hypopituitary Control and Complications Study (HypoCCS)) observational studies of GH treatment were assessed for incidence of SN. RESULTS The percentage of childhood cancer survivors treated with GH who developed a SN was 3.8% in pediatric GeNeSIS participants and 6.0% in adult HypoCCS participants. The estimated cumulative incidence of SN at 5 years of follow-up in these studies was 6.2 and 4.8% respectively. CONCLUSIONS The incidence of SN in GeNeSIS and HypoCCS GH-treated participants is similar to the published literature and is thus consistent with increased risk of SN in childhood cancer survivors treated with GH. As follow-up times were relatively short (<3 years), longer observation is recommended. Nevertheless, clinicians should be alerted to the possibility of increased risk of SN in childhood cancer survivors treated with GH and continue chronic surveillance.


Hormone Research in Paediatrics | 2013

Associations between Pituitary Imaging Abnormalities and Clinical and Biochemical Phenotypes in Children with Congenital Growth Hormone Deficiency: Data from an International Observational Study

Cheri Deal; Caroline Hasselmann; Roland Pfäffle; Alan G. Zimmermann; Charmian A. Quigley; Christopher J. Child; Elena P. Shavrikova; Gordon B. Cutler; Werner F. Blum

Background/Aims: Magnetic resonance imaging (MRI) is used to investigate the etiology of growth hormone deficiency (GHD). This study examined relationships between MRI findings and clinical/hormonal phenotypes in children with GHD in the observational Genetics and Neuroendocrinology of Short Stature International Study, GeNeSIS. Methods: Clinical presentation, hormonal status and first-year GH response were compared between patients with pituitary imaging abnormalities (n = 1,071), patients with mutations in genes involved in pituitary development/GH secretion (n = 120) and patients with idiopathic GHD (n = 7,039). Results: Patients with hypothalamic-pituitary abnormalities had more severe phenotypes than patients with idiopathic GHD. Additional hormonal deficiencies were found in 35% of patients with structural abnormalities (thyroid-stimulating hormone > adrenocorticotropic hormone > luteinizing hormone/follicle-stimulating hormone > antidiuretic hormone), most frequently in patients with septo-optic dysplasia (SOD). Patients with the triad [ectopic posterior pituitary (EPP), pituitary aplasia/hypoplasia and stalk defects] had a more severe phenotype and better response to GH treatment than patients with isolated abnormalities. The sex ratio was approximately equal for patients with SOD, but there was a significantly higher proportion of males (approximately 70%) in the EPP, pituitary hypoplasia, stalk defects, and triad categories. Conclusion: This large, international database demonstrates the value of classification of GH-deficient patients by the presence and type of hypothalamic-pituitary imaging abnormalities. This information may assist family counseling and patient management.

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Gordon B. Cutler

National Institutes of Health

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