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T 44: Current Japanese Diabetic Mellitus Prevalence and Glucose Clamp Studies for Global Anti-Diabetic Development

Poster Presenter

Eunhee Chung

Director, CSO
SOUSEIKAI Global
Japan

Objectives

As the prevalence of Diabetes Mellitus is consistently increasing in Japan, more and more anti-diabetic drugs are being tested, targeted for this potentially big market. To conduct safer and more efficient clinical trials for hypoglycemic drugs, we reviewed glucose clamp studies conducted in Japan.

Method

ORAL PRESENTATION SCHEDULED: Session 1A at 9:50 - 10:00 AM

We reviewed 27 Japanese glucose clamp studies from 1997 to 2016, and investigated the studies by the type of subjects, clamp, investigational drugs tested, and by the clamp duration. We also planned and conducted a hyperglycemic clamp study in healthy Japanese male subjects to verify the procedure.

Results

We conducted over 250 anti-diabetic studies as of Jan. 2016. Among these studies, 23 studies were conducted using the auto glucose clamp technique. We investigated these studies by the type of subjects (Type 1 Diabetes Mellitus (T1DM) patients, Type 2 Diabetes Mellitus (T2DM) patients, or healthy volunteers), clamp (Hypoglycemic, Euglycemic, or Hyperglycemic), type of investigational drugs tested, and by the clamp duration. A total of 576 subjects were enrolled for the glucose clamp studies, including 151 T1DM patients and 50 T2DM patients. Our glucose clamp procedures were performed from 2 hours in length to as long as 36 hours in length depending on the study design, and were well tolerated by all subjects. The investigational drugs that were tested using glucose clamp techniques varied from insulin inhalation to oral anti-diabetics. Hypoglycemic glucose clamps and hyperglycemic glucose clamps were approved by our central IRB without any issues, and conducted safely in T2DM patients. The data from the clinical research in healthy subjects verifying the study design and procedures of future hyperglycemic clamp studies showed that we were able to maintain a hyperglycemic condition for substantial study periods in healthy Japanese volunteers safely, and also that both insulin phase 1 and phase 2 increases were clearly detected in healthy Japanese volunteers.

Conclusion

In this study, we reviewed and evaluated all glucose clamp studies that used an artificial pancreas (STG-22, Nikkiso Co. Japan)conducted at SOUSEIKAI over the last 20 years. Hypoglycemic drugs are potentially risky when administered to subjects during clinical trials, and so it is essential that special attention be paid to monitor and, if needed, treat subjects accordingly. By using the glucose clamp technique, it is safer and more efficient to keep a subject’s blood glucose levels at a desired level for a certain amount of time. Also, by choosing one of the three methods of glucose clamp (Hypoglycemic , Euglycemic, or Hyperglycemic), it is possible to evaluate not only the PD of insulin preparations, but also insulin sensitivities/resistances, insulin secretory properties, and glucagon secretion in any type of diabetic patient or healthy subject. Although there are generally fewer T1DM patients in Japan when compared with other countries, we were able to conduct 7 glucose clamp studies in TIDM Japanese patients over the last 10 years, involving studies of up to 36 continuous hours on the glucose clamp for various types of insulin preparations. Our data suggested that it is important to control subject blood glucose levels thoroughly for the targeted level, especially during the night when a 36 hour-long glucose clamp is used; also it is crucial to adequately handle both rapid blood glucose level changes as well as frequent blood sampling when the glucose clamp studies for ultra rapid acting insulin preparations were used. We concluded that by using the glucose clamp technique, we can safely, accurately, and continuously monitor the effectiveness of hypoglycemic drugs, among others, in clinical trials. Furthermore, from the results of our hyperglycemic clamp research in healthy volunteers, it is suggested that the hyperglycemic glucose clamp technique is useful for evaluation of not only insulin preparations, but also various oral antidiabetic drugs.