The development and optimization of controlled release lipospheres (LS) from safe biocompatible behenic acid (BA) was performed for not only enhancing patient’s compliance against highly prevailed chronic diabetes but also to vanquish the insufficiencies of traditional methods of drug delivery. The Box‐Bhenken design (BBD) was utilized to statistically investigate the impact of formulation variables on percentage yield (Y1), entrapment efficiency (Y2), and SG‐release (Y3) from saxagliptin‐ (SG‐) loaded LS, and the chosen optimized LS were subjected to a comparative in vivo pharmacokinetic analysis against commercially available SG brand. The compatibility analysis performed by DSC and FTIR established a complete lack of interaction of formulation components with SG, while p‐XRD suggested a mild transformation of crystalline drug to its amorphous form during encapsulation process. The spherical, free flowing smooth surface LS having zeta potential of ‐32 mV and size range of 11‐20 μm were conveniently formulated. The obtained data for Y1 (30‐80%), Y2 (30‐70%), and Y3 (40‐90%) showed a best fit with quadratic model. The pharmacokinetics analysis of LS showed a significantly decreased Cmax of SG (75.63 ± 3.85) with a sufficiently elevated Tmax (10.53 h) as compared to commercial brand of SG (99.66 ± 2.97 ng/mL and 3.55 ± 2.18 h). The achievement of greater bioavailability of SG was most probably attributed to higher level of half‐life, mean residence time (MRT), and AUC0-24 for SG released from LS. Conclusively, the novel approach of SG‐loaded LS had successfully sustained the plasma SG level for a prolonged time without increasing Cmax which would ultimately bring an effective management of chronic diabetes.