Twelve weeks' treatment with diazoxide without insulin supplementation in Type 2 diabetes is feasible but does not improve insulin secretion.
OBJECTIVE
Treatment with K-ATP channel openers, such as diazoxide, can have beneficial effects on insulin secretion in both Type 1 and Type 2 diabetes. However, the precise conditions for obtaining beneficial effects without untoward events have not been determined. We tested the hypothesis that intermittent administration of diazoxide at bedtime for 12 weeks could produce beneficial effects in the absence of side-effects in Type 2 diabetic patients who were not taking insulin.


METHODS
After an 8-week run-in period, during which treatment with repaglinide and metformin was optimized, we randomized 26 patients to either diazoxide, 100 mg at bedtime, or placebo.


RESULTS
Side-effects were absent or minimal. HbA(1c) did not change. However day-time glucose concentrations by home glucose monitoring were approximately 1.5 mmol/l higher with diazoxide vs. placebo. Stimulation tests (C-peptide-glucagon and breakfast) did not indicate improved pancreatic B-cell function, except by posthoc analysis, in a subgroup of younger age.


CONCLUSIONS
Compared with previous results with diazoxide together with bedtime insulin, the present results are less favourable and indicate that concomitant insulin treatment is needed during intervention with K-ATP channel openers.
Radtke
M
M
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, University Hospital of Trondheim, Trondheim, Norway. maria.radtke@ntnu.no
Kollind
M
M
Qvigstad
E
E
Grill
V
V
D002219:Carbamates / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003981:Diazoxide / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D016896:Treatment Outcome
D002219:Carbamates; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; C072379:repaglinide; D008687:Metformin; D003981:Diazoxide