To describe glucose status changes in patients with acromegaly receiving somatostatin analog lanreotide as primary treatment. This retrospective, single-center study conducted during 1996-2008, included acromegalic patients receiving primary lanreotide treatment. Baseline and last follow-up visit assessments included glucose status (according to American Diabetes Association criteria), growth hormone (GH), and insulin-like growth factor-1 (IGF-1) levels. Glucose control was considered improved when fasting plasma glucose or antidiabetic treatments were reduced, and deteriorated if fasting glucose was the same/higher but with increased antidiabetic treatments. 42 patients (median age 50 years; range 29-75 years) were included. At baseline, 26 (62%) were normoglycemic, eight (19%) had impaired glucose tolerance/fasting glycemia, and eight (19%) had diabetes mellitus; family history of diabetes mellitus was significantly associated with abnormal glucose status. At final visit, the mean (SE) lanreotide dose was 108 (21) mg/month. Median treatment duration was 23 months, range 3-138 months, and 74% of patients received the 120-mg dose. Median GH levels decreased significantly (baseline, 12 [5-20] μg/l; final visit, 2.1 [1.0-4.7] μg/l; P < 0.0001); IGF-1 levels were age- and sex-normalized in 33% of patients. Glucose control deteriorated in seven patients (17%) and improved from abnormal levels in 10 (24%). Deterioration was associated with smaller GH decreases (median change, -3.4 μg/l vs. -10.7 μg/l, P = 0.014) and improvement with trend to lower BMI and younger age. During primary lanreotide treated acromegalic patients 60% had no change, 24% had an improvement and 17% had a worsening of glucose status. Deterioration was significantly associated with smaller GH decreases during primary lanreotide treatment.