Peptide therapeutics hold attractive potential. However, the proper stabilization of such therapeutics remains a major challenge. Some peptides are marginally stable and are prone to degradation. Therefore, in addition to chemical modifications that can be introduced in their sequence, a wide variety of excipients are added in the formulation to stabilize them, as is also done routinely for protein therapeutics. These substances are supposed to suppress peptide/protein aggregation and surface adsorption, facilitate their dispersion and additionally to provide physiological osmolality. Particular attention has to be paid to the choice of such excipients. Here we highlight the observation that in certain clinical situations, an excipient that is not totally inert can play a highly damaging role and mask (or even reverse) the beneficial effect of a molecule in clinical evaluation. This is the case, for instance, of trehalose, a normally safe excipient, which notably has proven to act as an activator of autophagy. This excipient, although used efficiently in several therapeutics, adversely impacted a phase IIb clinical trial for human and murine lupus, a systemic autoimmune disease in which it has been recently discovered that at the base line, autophagy is already abnormally enhanced in lymphocytes. Thus, in this particular pathology, while the peptide that was tested was active in lupus patients when formulated in mannitol, it was not efficient when formulated in trehalose. This observation is important, since autophagy is enhanced in a variety of pathological situations, such as obesity, diabetes, certain neurological diseases, and cancer.