Long-term glycaemic improvement after addition of metformin to insulin in insulin-treated obese type 2 diabetes patients.

AIM: To assess the adjunct effect of metformin to insulin in type 2 diabetes. METHODS: Obese and overweight type 2 diabetes patients treated with insulin for at least 1 year, and with poor glycaemic control (HbA1c > upper reference level + 2%), were included in a randomised, double-blind, placebo-controlled study. Patients were treated for 12 months with either metformin (850 mg b.i.d.) or placebo added to their usual insulin, which was stabilized during a 3-month placebo run-in period, but thereafter attempted to be unchanged. RESULTS: Thirty-seven patients were included. Two patients dropped out during run-in. There were no differences between the metformin (n = 16) and placebo (n = 19) group at baseline. Most patients received multiple insulin injections. Metabolic control was improved by addition of metformin. Mean change in HbA1c from baseline showed highly significant difference between groups at 3, 6, 9 and 12 months. Mean change (percentage units +/- s.d.) at 12 months was -1.1 +/- 0.7% vs. + 0.3 +/- 0.8% (p < 0.001) for HbA1c and -1.4 +/- 2.1 mmol/l vs. + 0.6 +/- 2.2 mmol/l (p = 0.025) for fasting blood glucose. Mean low density lipoprotein (LDL) cholesterol change differed slightly at 6 months, but not at 12 months. There were no changes in insulin dose, blood pressure, body weight, triglycerides, total- and high density lipoprotein (HDL) cholesterol, fibrinogen, C-peptide and laboratory safety variables, including serum B12. Combination therapy was well-tolerated with the same adverse event rate as insulin alone, but more patients with diarrhoea. CONCLUSION: Addition of metformin to insulin induced and maintained clinically significant and consistent long-term reduction of hyperglycaemia in obese, insulin-treated type 2 diabetes patients.

Early postoperative growth hormone levels: high predictive value for long-term outcome after surgery for acromegaly.

OBJECTIVES: To explore the prognostic value of early - within 1 week - postoperative growth hormone (GH) measurements with regard to outcome after surgery for acromegaly in a short- and a long-term perspective. DESIGN: Retrospective study of patients operated on between 1987 and 1998, including follow-up for up to 60 months. SETTING: University hospital. SUBJECTS: Sixty-eight patients with acromegaly. INTERVENTION: Pituitary surgery aiming at adenomectomy with preservation of pituitary function. MAIN OUTCOME MEASURES: The effect of the operation was evaluated after 3 months, mostly by means of an oral glucose load or by insulin-like growth factor 1 (IGF-1). The specificity, sensitivity and the predictive values of an early postoperative mean GH concentration 4.8 mU L-1 had a 77.8% predictive value for persistent or recurrent disease, compared with 85.7% for persistently increased SmC/IGF-1 and 68.8% for an abnormal GH release after TRH 3 months after surgery. In the short-term perspective, the specificity and the predictive value of an early GH 4.8 mU L-1 had a 94.4% sensitivity but a predicative value of only 63.0% for an unsatisfactory effect. CONCLUSION: Measurement of GH within 1 week after surgery is highly predictive for outcome of surgery for acromegaly. Specifically, an early mean GH 4.8 mU L-1 have a high sensitivity for persistent or recurrent disease in both the short- and long-term perspectives, but lower predictive value. The usefulness of the TRH test can be questioned.