Context: Administration of rhIGF-I/rhIGFBP-3 to patients with type 2 diabetes improves blood glucose and enhances insulin sensitivity. The changes in various components of the IGF system that occur in response to rhIGF-I/rhIGFBP-3 as well as the minimum effective does have not been determined.

Objective: To determine the dose of rhIGF-I/rhIGFBP-3 necessary to achieve a significant decrease in glucose and to determine the changes that occur in the IGF-II and ALS in response to treatment.

Design: Thirtynine insulin requiring type 2 diabetics were randomized to placebo or one of 6 groups that received different dosages of rhIGF-I/rhIGFBP-3. After 3 days in which insulin doses were adjusted to improve glucose control, a variable insulin dosage regimen was continued and either placebo or one of six dosages (0.125-2.0 mg/kg/day) of rhIGF-I/rhIGFBP-3 was administered for 7 days. All subjects were hospitalized and dietary intake as well as insulin dosage were controlled with instructions to treat to normal range targets.

Results: Fasting glucose was reduced in the groups that received either 1(32±5% reduction) or 2 mg/kg/day (40±6% reduction) of the complex. Mean daily glucose (4 determinations) was reduced by 26±4% in the 1 mg/kg group and by 33±5% in the 2 mg/kg group compared to 18±4% in the placebo group. Total serum IGF-I increased between 2.0±0.3 and 5.7±1.3 fold by day 8. IGFBP-3 concentrations increased significantly only in the 2 mg/kg group. IGF-II concentrations declined to values that were between 27±4 and 64±7% below baseline. Acid labile subunit (ALS) concentrations declined significantly in the 3 highest dose groups. The sum of the IGF-I + IGF-II concentrations was significantly increased at the two highest dosages. There were very few drug associated adverse events reported in this study with the exception of hypoglycemia which occurred in 15 subjects who had received rhIGF-I/rhIGFBP-3 treatment.

Conclusion: Administration of rhIGF-I/rhIGFBP-3 resulted in a redistribution of the amount of IGF-I and IGF-II that bound to IGFBP-3. Fasting and mean daily blood glucose were reduced significantly in the two highest dosage groups. The results suggest that both the total concentration of IGF-I as well as its distribution in blood may determine the extent to which insulin sensitivity is enhanced.