Background: The prevalence of type-2 diabetes mellitus (T2DM) is rapidly increasing and the majority of diabetics are obese. Many of the therapeutic options for T2DM can cause further weight gain. Concerns about weight gain adversely affect patients' willingness to begin and continue treatment with glucose-lowering medications, such as thiazolidinediones insulin, and sulfonylureas. The aim of this work was to study the influence of DPP-4 inhibitors on weight of newly diagnosed T2DM patients in Egypt. Subjects and methods: This study included 357 newly diagnosed T2DM patients from the private sector of Cairo & Fayoum. They were divided into three groups according to the treatment strategy. Results: patients treated with DPP4-1 +/- metformin achieved a reduction of A1c by 1.2 -1.7 gm % and weight loss of 3.2-4.6 kgs in one year compared to the control group who achieved greater HbA1c (1.5 -2.2 gm% p < 0.05) and weight gain(2.2 – 3.5 kgs p < 0.0001) the weight changes started within the first month, reached its maximum in 6 months then followed by a sligh rebound weight gain Conclusion: Dipeptidyl peptidase-4 (DPP-4) inhibitors were effective in improving glycemic control with significant weight reduction in newly diagnosed Egyptian T2DM patients specially when combined with metformin.