Among patients with osteoporosis who were at high risk for fracture, bone mineral density increased more in patients receiving teriparatide than in those receiving alendronate. (ClinicalTrials.gov number, NCT00051558 [ClinicalTrials.gov].).

No abstract

OBJECTIVE -To determine the safety and efficacy of the long-acting analog insulin glargine compared with NPH insulin in patients with type 2 diabetes who were previously treated with insulin alone. RESEARCH DESIGN AND METHODS-A total of 518 subjects with type 2 diabetes who were receiving NPH insulin with or without regular insulin for postprandial control were randomized to receive insulin glargine (HOE 901) once daily (n ϭ 259) or NPH insulin once or twice daily (n ϭ 259) for 28 weeks in an open-label, multicenter trial. Doses were adjusted to obtain target fasting glucose Ͻ6.7 mmol/l. At study end point, the median total daily insulin dose in both treatment groups was 0.75 IU/kg. RESULTS -The treatment groups showed similar improvements in HbA 1c from baseline to end point on intent-to-treat analysis. The mean change (means Ϯ SD) in HbA 1c from baseline to end point was similar in the insulin glargine group (Ϫ0.41 Ϯ 0.1%) and the NPH group (Ϫ0.59 Ϯ 0.1%) after patients began with an average baseline HbA 1c of ϳ8.5%. The treatments were associated with similar reductions in fasting glucose levels. Overall, mild symptomatic hypoglycemia was similar in insulin glargine subjects (61.4%) and NPH insulin subjects (66.8%). However, nocturnal hypoglycemia in the insulin glargine group was reduced by 25% during the treatment period after the dose-titration phase (26.5 vs. 35.5%, P ϭ 0.0136). Subjects in the insulin glargine group experienced less weight gain than those in the NPH group (0.4 vs. 1.4 kg, P Ͻ 0.0007).CONCLUSIONS -In patients with type 2 diabetes, once-daily bedtime insulin glargine is as effective as once-or twice-daily NPH in improving and maintaining glycemic control. In addition, insulin glargine demonstrates a lower risk of nocturnal hypoglycemia and less weight gain compared with NPH insulin. Diabetes Care 24:631-636, 2001I nsulin treatment can improve and maintain glycemic control, preventing long-term complications in type 2 diabetes (1-3). Over time, most patients with type 2 diabetes experience progressive ␤-cell dysfunction and will require insulin therapy, either alone or in combination with oral agents, for satisfactory glycemic control (4). Attempts to mimic physiologic patterns of basal insulin secretion have been difficult because most currently available insulins have disadvantages, including variable absorption, pronounced peaks after injection, and abbreviated durations of action (5-8).The novel recombinant insulin analog insulin glargine (HOE 901; 21b-L-Arg-human insulin) is a modification of human insulin in which two arginines are added to the B-chain and glycine is substituted for asparagine at the A21 position of the insulin molecule. These changes cause a shift of the isoelectric point to a neutral pH (9 -11), precipitation at physiologic tissue pH, and increased hexamer stability, resulting in delayed absorption and a flat profile after injection, compared with the shorter duration of action and early peak of NPH insulin (9 -12). Short-term clinical trials in patients with type 1...

Two distinct options for the management of osteoporosis lead to increases in BMD by opposite mechanisms of action on bone remodeling.

Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12-24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo.Introduction: Recombinant teriparatide [human PTH(1-34)], a bone formation agent for the treatment of osteoporosis when given once daily subcutaneously, increases biochemical markers of bone turnover and activation frequency in histomorphometry studies. Materials and Methods:We studied the mechanisms underlying this bone-forming action of teriparatide at the basic multicellular unit by the appearance of cement lines, a method used to directly classify surfaces as modeling or remodeling osteons, and by the immunolocalization of IGF-I and IGF-II. Transiliac bone biopsies were obtained from 55 postmenopausal women treated with teriparatide 20 or 40 g or placebo for 12-24 months (median, 19.8 months) in the Fracture Prevention Trial. Results: A dose-dependent relationship was observed in modeling and mixed remodeling/modeling trabecular hemiosteons. Trabecular and endosteal hemiosteon mean wall thicknesses were significantly higher in both teriparatide groups than in placebo. There was a dose-dependent relationship in IGF-II immunoreactive staining at all bone envelopes studied. The greater local IGF-II presence after treatment with teriparatide may play a key role in stimulating bone formation. Conclusions: Direct evidence is presented that 12-24 months of teriparatide treatment induced modeling bone formation at quiescent surfaces and resulted in greater bone formation at remodeling sites, relative to placebo.