OBJECTIVE Basal glucagon-like peptide-1 (GLP-1) concentrations seem to be attenuated in obese subjects, although statistical significance is unclear. Only a few studies have investigated the effect of weight reduction on GLP-1 concentrations and have found unclear results. The aim of the present study was to determine whether subjects who lose weight on a hypocaloric diet experience the same change in circulating GLP-1 levels as subjects who do not lose weight. METHODS A population of 99 obese nondiabetic outpatients was analyzed in a prospective way. Weight and blood pressure were determined. Basal glucose, C-reactive protein, insulin, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and basal GLP-1 blood levels were measured before and after 3 months of hypocaloric diet. Bipolar impedance examination was performed in all patients to assess body composition. The lifestyle modification program consisted of a hypocaloric diet (1,520 kcal, 52% carbohydrates, 25% lipids and 23% proteins). The exercise program consisted of aerobic exercise for at least 3 times per week (60 min each). RESULTS Ninety-nine patients (20 male/79 female) gave informed consent and were enrolled in the study. Fourteen patients (2 male/12 female) did not lose weight (group I: weight increase of 2 +/- 1.1 kg, NS) and 75 patients (18 male/67 female) lost weight (group II, weight loss of 4 +/- 1.6 kg, p < 0.05). Weight, body mass index, fat mass, waist circumference, insulin, HOMA, LDL cholesterol, triglycerides and systolic blood pressure improved in group II, without significant statistical changes in group I. In group I, basal GLP-1 levels remained unchanged (7.4 +/- 3.1 vs. 7.15 +/- 3.6 ng/ml, NS). In group II, GLP-1 levels decreased significantly (8.4%, 6.88 +/- 2.5 vs. 6.3 +/- 2.4 ng/ml, p < 0.05). In the multivariate analysis with a dependent variable (levels of GLP-1 after hypocaloric diet adjusted by age and sex), only insulin levels remained as an independent predictor in the model (F = 5.9; p < 0.05), with an increase of 0.6 ng/ml (CI 95%: 0.1-1.1) in GLP-1 concentrations with each 1-mIU/ml increase of insulin. CONCLUSIONS Hypocaloric diet decreased GLP-1 levels in patients with weight loss with a significant improvement in anthropometric parameters and cardiovascular risk factors. Nevertheless, patients without weight loss after dietary treatment exhibited unchanged GLP-1 levels. Basal insulin correlates with basal GLP-1.