Researchers assess the safety of intranasal insulin as a treatment for type 2 diabetes-associated cognitive impairment in aging adult populations.
Type 2 diabetes mellitus is a risk factor for neurological and cardiovascular complications of accelerated brain aging, dementia, and stroke. Individuals age 65 or older are affected more than any other age group globally. This aging population has a higher incidence of cognitive dysfunction, impaired executive function, poor self-management, and greater fall risk. Brain insulin resistance is the leading cause of cognitive impairment. Recently, intranasal insulin has become a potentially beneficial treatment for cognitive impairment. Intranasal insulin penetrates the blood-brain barrier and reaches the insulin receptors of the brain to improve neuronal activity. Studies suggest that intranasal insulin may enhance functional connectivity, the flow of circulation, and vascular tone per Zhang H et al. 2015.
The purpose of the study was to demonstrate the short and long-term safety of intranasal insulin use in participants with type 2 diabetes mellitus from the MemAID trial. Researchers conducted the sub-study analysis as a double-blinded randomized control trial with a population of 86 screened participants. Subjects were randomized into two treatment arms. Treatment arms consisted of the intranasal insulin arm and the placebo arms with varying add-on antidiabetic therapies. Participants were required to self-monitor glucose levels and log medication use, meals, and activities. Researchers excluded participants if they had a history of insulin use, insulin allergy, type 1 diabetes, or severe hypoglycemia. Other exclusion criteria included a history of dementia, liver failure or transplant, renal failure or transplant, MMSE score <20, or acute medical condition within the past six months. Using the IPro2 continuous glucose monitoring system, clinicians recorded short-term glucose data. In addition, the clinicians collected long-term safety measures, including fasting plasma glucose, insulin, and HbA1c, at screening, treatment, and post-treatment.
After researchers applied exclusion criteria, 9 participants started treatment with five subjects in the intranasal insulin arm and four subjects in the placebo arm. Five subjects total completed the treatment and follow-up. Researchers observed that intranasal insulin use did not affect glucose profile or cause hypoglycemia for two hours. Long-term safety revealed decreased HbA1c levels, plasma insulin, and fasting glucose levels from baseline to post-treatment. Subjects tolerated intranasal insulin with no serious adverse events. Two events of hypoglycemia occurred in the intranasal insulin group and seven in the placebo group. Two events of asymptomatic level-2 hypoglycemia occurred in both the intranasal insulin and placebo groups.
Researchers found intranasal insulin therapy observations safe with no adverse events in aging participants with insulin-dependent type 2 diabetes mellitus. There was no change in the glycemic profile. Lower HbA1c and insulin levels suggest the need for further studies on treatment with intranasal insulin. Short and long-term safety data provided data for future more extensive studies assessing the safety of concurrent use of intranasal insulin and subcutaneous insulin.
- Subjects tolerated intranasal insulin with no adverse events.
- Long-term safety outcomes of intranasal insulin showed lower HbA1c, plasma insulin, and fasting glucose levels.
- Further study is needed on the concurrent use of intranasal insulin and subcutaneous insulin.
Becerra, L. A et al. (2021, June). Long-term Safety of Intranasal Insulin in Insulin-Dependent Type 2 Diabetes: A Safety Sub-study of Memory Advancement by Intranasal Insulin in Type 2 Diabetes (MemAID) Trial. American Diabetes Association. (Requires ADA Symposium login.)
B Galindo-Mendez et al. Memory advancement by intranasal insulin in type 2 diabetes (MemAID) randomized controlled clinical trial: Design, methods and rationale. Jan. 2020. https://pubmed.ncbi.nlm.nih.gov/31923471/
Torré Anderson, II, Fourth Year Doctor of Pharmacy Candidate, Florida A&M University College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health