Career choice for Chinese medical graduate: Safety Physician Patrick Hu, M.D.

Introduction The goal is to talk about the choice available to the Chinese graduate with or without US Ph.D.  How to become licensed physician. How to operate a private medical clinic and how to be a Pharmaceutical physician.

New Zealand, 2017

Study Overview Patients with type 2 diabetes at high cardiovascular risk received either once-weekly semaglutide, a glucagon-like peptide 1 analogue, or placebo. The rate of a first occurrence of cardiovascular death, nonfatal MI, or nonfatal stroke was significantly lower with semaglutide.

Cardiovascular Outcomes. Figure 1 Cardiovascular Outcomes. Shown are Kaplan–Meier plots of the primary outcome (a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) (Panel A), nonfatal myocardial infarction (Panel B), nonfatal stroke (Panel C), and death from cardiovascular causes (Panel D). The trial included a planned observation period of 109 weeks for all patients (a 104-week treatment period with a 5-week follow-up period). In Panel C, there were no events in the semaglutide group after week 104. Insets show the same data on an expanded y axis. Marso SP et al. N Engl J Med 2016;375:1834-1844

Glycated Hemoglobin and Body Weight. Figure 2 Glycated Hemoglobin and Body Weight. Shown are the mean values for glycated hemoglobin (Panel A) and body weight (Panel B) during the trial period. The I bars represent standard errors. Data were estimated on the basis of scheduled visits in the full analysis set with the use of a mixed model for repeated measures with treatment group (semaglutide doses of 0.5 mg and 1.0 mg and corresponding placebo doses) and all possible combinations of stratification factors used for randomization as fixed factors. Marso SP et al. N Engl J Med 2016;375:1834-1844

Characteristics of the Patients at Baseline. Table 1 Characteristics of the Patients at Baseline. Marso SP et al. N Engl J Med 2016;375:1834-1844

FDA Type C meeting, 2016

Primary and Secondary Cardiovascular and Microvascular Outcomes. Table 2 Primary and Secondary Cardiovascular and Microvascular Outcomes. Marso SP et al. N Engl J Med 2016;375:1834-1844

Selected Adverse Events. Table 3 Selected Adverse Events. Marso SP et al. N Engl J Med 2016;375:1834-1844

With Classmates, 2015

Summary slide Discussed what a Safety Physician do: Protect the patient by knowledge and extensive experience. Make sure all the regulatory requirement is fullfiled (required by law around the World. Career Choice for Chinese medical graduate.

Any Questions?

Backup slides

China, 2016

Conclusions In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide.

Original Article Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes Bernard Zinman, M.D., Christoph Wanner, M.D., John M. Lachin, Sc.D., David Fitchett, M.D., Erich Bluhmki, Ph.D., Stefan Hantel, Ph.D., Michaela Mattheus, Dipl. Biomath., Theresa Devins, Dr.P.H., Odd Erik Johansen, M.D., Ph.D., Hans J. Woerle, M.D., Uli C. Broedl, M.D., Silvio E. Inzucchi, M.D., for the EMPA-REG OUTCOME Investigators N Engl J Med Volume 373(22):2117-2128 November 26, 2015

Study Overview In this study, the addition of empagliflozin, an inhibitor of sodium– glucose cotransporter 2, to standard care reduced cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk.

Cardiovascular Outcomes and Death from Any Cause. Figure 1 Cardiovascular Outcomes and Death from Any Cause. Shown are the cumulative incidence of the primary outcome (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) (Panel A), cumulative incidence of death from cardiovascular causes (Panel B), the Kaplan–Meier estimate for death from any cause (Panel C), and the cumulative incidence of hospitalization for heart failure (Panel D) in the pooled empagliflozin group and the placebo group among patients who received at least one dose of a study drug. Hazard ratios are based on Cox regression analyses. Zinman B et al. N Engl J Med 2015;373:2117-2128

Subgroup Analyses for the Primary Outcome and Death from Cardiovascular Causes. Figure 2 Subgroup Analyses for the Primary Outcome and Death from Cardiovascular Causes. Shown are the results of a prespecified Cox regression analysis of data for subgroups of patients with respect to the primary outcome. Subgroup analyses of death from cardiovascular causes were conducted post hoc. P values are for tests of homogeneity of between-group differences among subgroups with no adjustment for multiple testing. The size of the ovals is proportional to the number of patients in the subgroup. ACE denotes angiotensin-converting enzyme, ARB angiotensin-receptor blocker, DBP diastolic blood pressure, and SBP systolic blood pressure. Zinman B et al. N Engl J Med 2015;373:2117-2128

Glycated Hemoglobin Levels. Figure 3 Glycated Hemoglobin Levels. Shown are mean (±SE) glycated hemoglobin levels in the three study groups, as calculated with the use of a repeated-measures analysis as a mixed model of all data for patients who received at least one dose of a study drug and had a baseline measurement. The model included baseline glycated hemoglobin as a linear covariate, with baseline estimated glomerular filtration rate, geographic region, body-mass index, the last week a patient could have had a glycated hemoglobin measurement, study group, visit, visit according to treatment interaction, and baseline glycated hemoglobin according to visit interaction as fixed effects. Zinman B et al. N Engl J Med 2015;373:2117-2128

Primary and Secondary Cardiovascular Outcomes. Table 1 Primary and Secondary Cardiovascular Outcomes. Zinman B et al. N Engl J Med 2015;373:2117-2128

Adverse Events. Table 2 Adverse Events. Zinman B et al. N Engl J Med 2015;373:2117-2128

Conclusions Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care.

Original Article Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes Steven P. Marso, M.D., Stephen C. Bain, M.D., Agostino Consoli, M.D., Freddy G. Eliaschewitz, M.D., Esteban Jódar, M.D., Lawrence A. Leiter, M.D., Ildiko Lingvay, M.D., M.P.H., M.S.C.S., Julio Rosenstock, M.D., Jochen Seufert, M.D., Ph.D., Mark L. Warren, M.D., Vincent Woo, M.D., Oluf Hansen, M.Sc., Anders G. Holst, M.D., Ph.D., Jonas Pettersson, M.D., Ph.D., Tina Vilsbøll, M.D., D.M.Sc., for the SUSTAIN-6 Investigators N Engl J Med Volume 375(19):1834-1844 November 10, 2016