Caloric Intake, Appetite, and Body Composition Outcomes of Long-Term Intranasal Insulin (INI) Administration: A Substudy of the Memory Advancement by INI in Type 2 Diabetes (MemAID) Study

Centrally administered insulin stimulates the reward system to reduce appetite in response to food intake in animal studies. Previous studies in humans have shown mixed results, suggesting INI may decrease appetite, body fat, and weight in non-obese and young males, but this hypothesis has not been tested in elderly with and without type 2 diabetes. This randomized, doubled blind trial consisted of 24 weeks of treatment with either 40 IU of INI (Novolin® R) or Placebo (sterile saline) once daily in elderly adults from MemAID. The primary outcome was the INI effect on food intake, and secondary outcomes included appetite, anthropometric measures, and body composition. In exploratory analyses, we tested the effect of INI on these outcomes when contrasting individuals by gender, BMI, and type 2 diabetes. Randomization included 121 participants, of which 89 (42 women, 53%; age 65±9 years; 46 INI, 52%; 38 diabetes, 43%) completed baseline and at least one intervention visit. Of those, 70 completed treatment (31 diabetes). There was no INI effect on caloric intake on any of the secondary outcomes. Sub-analyses comparing participants within the INI group also showed no differential effect on primary and secondary outcomes. We did not observe an overall INI effect on food intake, appetite, anthropometric measures, and body composition. However, whether insulin resistance may limit the effect of INI in participants without type 2 diabetes remains to be explored. Further research on the mechanisms underlying the potential effect of INI on appetite centrally is warranted (NCT02415556). Disclosure L. Aponte becerra: None. F. Khan: None. L. H. Ngo: Consultant; Self; Five Islands Consulting, Other Relationship; Self; Radiological Society of America. V. Novak: Advisory Panel; Spouse/Partner; Endonovo Therapeutics, Inc., Consultant; Spouse/Partner; Dysimmune Foundtation, Other Relationship; Spouse/Partner; Oxford University Press. Memaid collaborators (a. gavrieli, j. upadhyay): n/a. C. Mantzoros: Advisory Panel; Self; Amgen Inc., GENFIT, Intercept Pharmaceuticals, Inc., Novo Nordisk, Regeneron Pharmaceuticals Inc. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK103902); U.S. Food and Drug Administration (IND107690); Novo Nordisk (ISS-001063), Medtronic (NERP15-0310); World Health Organization (UTN-U111-1175-1588)