Improved prandial glucose control with lower risk of hypoglycemia with nateglinide than with glibenclamide in patients with maturity-onset diabetes of the young type 3.
OBJECTIVE
To study the effect of the short-acting insulin secretagogue nateglinide in patients with maturity-onset diabetes of the young type 3 (MODY3), which is characterized by a defective insulin response to glucose and hypersensitivity to sulfonylureas.


METHODS
We compared the acute effect of nateglinide, glibenclamide, and placebo on prandial plasma glucose and serum insulin, C-peptide, and glucagon excursions in 15 patients with MODY3. After an overnight fast, they received on three randomized occasions placebo, 1.25 mg glibenclamide, or 30 mg nateglinide before a standard 450-kcal test meal and light bicycle exercise for 30 min starting 140 min after the ingestion of the first test drug.


RESULTS
Insulin peaked earlier after nateglinide than after glibenclamide or placebo (median [interquartile range] time 70 [50] vs. 110 [20] vs. 110 [30] min, P = 0.0002 and P = 0.0025, respectively). Consequently, compared with glibenclamide and placebo, the peak plasma glucose (P = 0.031 and P < 0.0001) and incremental glucose areas under curve during the first 140 min of the test (P = 0.041 and P < 0.0001) remained lower after nateglinide. The improved prandial glucose control with nateglinide was achieved with a lower peak insulin concentration than after glibenclamide (47.0 [26.0] vs. 80.4 [71.7] mU/l; P = 0.023). Exercise did not induce hypoglycemia after nateglinide or placebo, but after glibenclamide six patients experienced symptomatic hypoglycemia and three had to interrupt the test.


CONCLUSIONS
A low dose of nateglinide prevents the acute postprandial rise in glucose more efficiently than glibenclamide and with less stimulation of peak insulin concentrations and less hypoglycemic symptoms.
Tuomi
Tiinamaija
T
Department of Medicine/Diabetology, Helsinki University Central Hospital, P.O. Box 340, FIN-00029 HUS, Helsinki, Finland. tiinamaija.tuomi@hus.fi
Honkanen
Elina H
EH
Isomaa
Bo
B
Sarelin
Leena
L
Groop
Leif C
LC
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D002096:C-Peptide / Q000097:blood / Q000187:drug effects; D018592:Cross-Over Studies; D003510:Cyclohexanes / Q000494:pharmacology* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D005934:Glucagon / Q000097:blood / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019518:Postprandial Period / Q000187:drug effects
D001786:Blood Glucose; D002096:C-Peptide; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D007328:Insulin; D000077715:Nateglinide; D010649:Phenylalanine; D005934:Glucagon; D005905:Glyburide