Background: Acromegaly is characterized by an insulin resistance condition. There is a significant difference between the different types of therapy in relation to the glycometabolic framework. The blinded continuous glucose monitoring system (CGMS), throughout a period of maximum 6 days for a total of 288 glycemic registrations per day, identifies glycemic excursions and could constitute a valid device to understand the 24-hour glycemic profiles. Aim of the study: To compare the oral glucose tolerance test (OGTT) and CGMS methods in acromegalic patients to evaluate their glycemic profiles, in relation to different treatments for acromegaly. Methods: Thirty-five acromegalic patients were divided into 18 somatostatin analogs (SSA), 9 pegvisomant, and 8 successfully surgically treated. A 72-hour CGM was performed and, immediately after, an OGTT. Results: Results obtained from OGTT: 11/35 impaired fasting glucose, 6/35 impaired glucose tolerance, and 4/35 diabetes mellitus. A positive significant correlation was demonstrated between the OGTT peak and CGM peak in all of the patients, CGM peak of patients treated with SSA and those surgically treated, OGTT average and CGM area under concentration–time curve (AUC) for hyperglycemia of patients treated with SSA and those surgically treated, and CGM AUC for hyperglycemia of patients treated with SSA and those surgically treated. Conclusions: Our results show a significantly higher response in terms of mean and peak OGTT in patients treated with SSA, both compared to the CGM study, and compared to the group of patients receiving pegvisomant. The CGM system could represent an instrument for the evaluation of the glycemic trend of acromegalic patients.