OBJECTIVE: The effects of GH replacement on glucose metabolism in GH-deficient (GHD) adults in clinical practice are not well defined. Therefore, we assessed GH treatment effects on fasting plasma glucose (FPG) and haemoglobin A1c (A1c) concentrations in GHD adults in a clinical setting. DESIGN: Post-hoc analysis of the observational Hypopituitary Control and Complications Study conducted at 157 US centres (1997-2002). PATIENTS: GH-deficient adults who were GH-naïve at study entry and had at least two FPG measurements. MEASUREMENTS: Effect of GH treatment on the frequency and time course of abnormal FPG (> or =5.6 mmol/l) development, FPG normalization, progression of increased FPG and abnormal follow-up A1c (>6%) values in GHD patients treated with GH (n = 403) or untreated (n = 169) at their physician's discretion. RESULTS: In subjects without pre-existing diabetes mellitus, development of an abnormal FPG tended to occur in a greater percentage of GH-treated than untreated subjects (35.3% versus 24.5, P = 0.06). Additionally, GH treatment was associated with a mild, transient increase in FPG and shorter time to development of an abnormal FPG in these subjects (P < 0.01). Most ( approximately 80%) abnormal FPG values were below 7 mmol/l and normalized in 69% of GH-treated subjects without diabetes. Treatment with GH had no effect on the rate of FPG normalization, progression of increased FPG or abnormal follow-up A1c values. CONCLUSIONS: Initiation of GH replacement in GHD adults was associated with a mild increase in FPG that often normalized spontaneously. Nevertheless, clinicians should monitor FPG in patients receiving GH treatment.