Fused Deposition Modelling (a.k.a. FDM-3D printing) has been previously employed in the development of personalized medicines with unique properties and release behavior. In the present work, a bilayer dosage form containing two anti-diabetic drugs with different daily dosage regimens; i.e. metformin and glimepiride, was manufactured via FDM 3D printing, studied using a variety of techniques and characterized in vitro. Metformin and glimepiride were embedded in Eudragit® RL sustained release layer and polyvinyl alcohol (PVA) layer respectively. Incorporation of more than one API's into the formulation is desirable, as it increases patient compliance and reduces cost of treatment, especially when distinct dosages of API's can be adjusted individually in situ, in order to meet each patient's specific needs, a capability provided by 3D printing. A number of different preparation methods, which involved different plasticizers and extruders, were tested on manufacturing Eudragit® RL drug-loaded filaments for printing the sustained release layer. The properties of the produced filaments were assessed by means of mechanical and physicochemical characterization techniques and the filaments with the optimum properties were used for printing. Microfocus computed tomography (μCT) imaging-based actual/nominal comparison analysis showed a printing accuracy ranging between −100, +200 μm, while X-ray (XRD) diffractograms revealed the incorporation of the (initially crystalline) API's as amorphous dispersions into polymer matrices. Dissolution tests showed sufficient drug release for both drugs in desired time frames (75 min for glimepiride and 480 min for metformin). The results from the current study emphasize the potentiality of 3D printing technology for tailor-made solid dosage forms for combined pharmacotherapy, even at the cases when API's with different desirable release profiles are employed.