Pharmacokinetics, pharmacodynamics, and dose-response relationship of repaglinide in type 2 diabetes.
BACKGROUND
The pharmacodynamics and dose-response relationship of repaglinide, a novel oral hypoglycemic agent, were evaluated in steady-state treatment of patients with type 2 diabetes.


METHODS
Efficacy of repaglinide (0.25 mg, 0.5 mg, 1 mg, 2 mg, and 4 mg) was compared to that of placebo in a double-blind, randomized, parallel-group, 4-week dose-response clinical trial in 143 patients. Repaglinide was administered 15 minutes before meals (breakfast, lunch, and dinner). Efficacy of repaglinide therapy was assessed by measuring changes from baseline in mean levels of blood glucose (BGmean), fasting serum glucose (FSG), and mean levels of serum insulin (INSmean).


RESULTS
Blood concentrations of repaglinide were proportional to the dose administered. INSmean values increased in all repaglinide treatment groups (by 6.7 to 12.9 microU/mL). All doses of repaglinide significantly decreased values of BGmean and FSG as compared with the placebo group. BGmean values stabilized between the second and third week of repaglinide treatment. A well-defined dose-response relationship was observed for BGmean and FSG values. All doses of repaglinide were well tolerated, and there were no serious adverse events.


CONCLUSIONS
These findings show that the therapeutic reduction of serum glucose levels produced by repaglinide is dose-dependent for the 0.25- to 4-mg dose range. All doses of repaglinide tested were effective and well tolerated in patients with type 2 diabetes.
Strange
P
P
Novo Nordisk Pharmaceuticals, Inc., Princeton, New Jersey, USA. pstr@nnpi.com
Schwartz
S L
SL
Graf
R J
RJ
Polvino
W
W
Weston
I
I
Marbury
T C
TC
Huang
W C
WC
Goldberg
R B
RB
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002219:Carbamates / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005006:Ethnicity; D005215:Fasting; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D010919:Placebos; D014481:United States
D001786:Blood Glucose; D002219:Carbamates; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; D010919:Placebos; C072379:repaglinide