There is indirect evidence of unfavorable effects of parathyroid hormone (PTH) on glucose metabolism. Teriparatide (recombinant human PTH 1-34-TPTD) has recently been available for the treatment of osteoporosis. The aim of this prospective study was to evaluate the acute and chronic effect of TPTD on blood glucose and insulin levels in women with established osteoporosis. Twenty-three postmenopausal women with established osteoporosis (mean age 65.6+/-1.8 years) received daily injections of 20 mg TPTD for six months. Three oral glucose tolerance tests (OGTT) were performed: one day before the first injection (OGTT-basal), one hour after (OGTT-acute) and six months after initiation of therapy (OGTT-chronic). There were significant differences between the OGTT-basal and OGTT-acute values in glucose at 90 min (168.3+/-9.8 vs. 180.6+/-9.2, p<0.05) and 120 min (152.0+/-8.7 vs. 170.5+/-7.8, p<0.01), between the OGTT-basal and OGTT-chronic values for glucose at 90 min (168.3+/-9.8 vs. 184.5+/-13.3, p<0.05) and between the OGTT-basal and OGTT-acute for insulin at 90 min (56.7+/-7.4 vs. 68.7+/-8.2, p<0.01). These differences remained significant for the subgroup of patients with normal (n=8) but not impaired glucose tolerance or diabetes mellitus (n=15). TPTD seems to have an acute, subclinical adverse impact on stimulated glucose levels, possibly due to insulin resistance. This impact tends to subside when TPTD is continued on a chronic basis.