Long-term beneficial effects of glipizide treatment on glucose tolerance in subjects with impaired glucose tolerance.
OBJECTIVE
To assess the efficacy and long-term effects of glipizide treatment on glucose and insulin metabolism in individuals with impaired glucose tolerance (IGT).


METHODS
Thirty-seven first-degree relatives of patients with type 2 diabetes fulfilling WHO criteria for IGT were randomized to treatment with either glipizide 2.5 mg once daily or matching placebo for 6 months. A 75 g, 2-h oral (OGTT) and 60 min intravenous glucose tolerance test (IVGTT) were performed at baseline and after 6 months. The subjects were followed up for another 12 months after discontinuation of treatment and a repeat OGTT was performed at 18 months.


RESULTS
Thirty-three subjects fulfilled the study. Markers of insulin sensitivity - i.e. fasting insulin and HOMA(IR)-index - improved in the glipizide group (P = 0.04 and 0.02 respectively) as well as HDL cholesterol (P = 0.05) compared with placebo group after 6 months. At 18 months, both fasting and 2 h glucose concentrations were significantly lower in the glipizide group compared with the placebo group (P = 0.04 and 0.03 respectively). The prevalence of type 2 diabetes was 29.4% in the placebo group and 5.9% in the glipizide group at 18 months. This equals an 80% relative risk reduction in the active treatment group.


CONCLUSIONS
Short-term treatment with glipizide improves glucose and insulin metabolism in subjects with IGT primarily by improving insulin sensitivity mediated by lowering glucose toxicity, thereby providing the beta cells rest. Larger studies are needed to establish whether these effects are sufficient to prevent progression to manifest type 2 diabetes and associated cardiovascular morbidity in subjects at increased risk of developing type 2 diabetes.
Eriksson
J G
JG
Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland. johan.eriksson@ktl.fi
Lehtovirta
M
M
Ehrnström
B
B
Salmela
S
S
Groop
L
L
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000517:prevention & control; D018450:Disease Progression; D004311:Double-Blind Method; D005192:Family Health; D005260:Female; D005913:Glipizide / Q000009:adverse effects / Q000627:therapeutic use*; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D005913:Glipizide