Trial results for a Phase 2 pilot study (NCT05081219) investigating empagliflozin, alone and in combination with intranasal insulin, for mild cognitive impairment and Alzheimer's disease were posted on ClinicalTrials.gov on 2025-10-21. The study reported 0 treatment-related serious adverse events across all treatment groups.
Background
Empagliflozin is an SGLT2 inhibitor. This pilot study, titled 'SNIFF - Combo INI+EMPA Trial,' aimed to gather preliminary safety and efficacy data for empagliflozin, both singularly and in combination with intranasal insulin, in adults with preclinical Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) or early AD. The trial explored therapeutic approaches to correct bioenergetic and vascular dysfunction in these conditions.
Trial design
The 'SNIFF - Combo INI+EMPA Trial' (NCT05081219) was a Phase 2, completed pilot study that enrolled 47 participants. The study investigated treatments for individuals with Mild Cognitive Impairment, Cognitive Impairment, and Alzheimer Disease. Participants received one of four interventions: intranasal insulin (Humulin® R U-100), empagliflozin 10 mg, a combination of intranasal insulin and empagliflozin, or placebo (insulin diluent and capsules).
Key results
The trial results focused on safety and preliminary cognitive outcomes. For the outcome of 'Number of Participants With Treatment-Related Serious Adverse Events as Assessed by CTCAE v5.0':
- In the Intranasal Insulin and Empagliflozin Placebo group, 0 participants experienced serious adverse events.
- In the Empagliflozin and Intranasal Insulin Placebo group, 0 participants experienced serious adverse events.
- In the Intranasal Insulin and Empagliflozin group, 0 participants experienced serious adverse events.
- In the Placebo group, 0 participants experienced serious adverse events.
Regarding cognitive outcomes, for 'Change in the Preclinical Alzheimer Cognitive Composite V5 (PACC5) Z-Score':
- The Intranasal Insulin and Empagliflozin Placebo group showed a mean change of 0.2 z-score (Standard Deviation: 0.1).
- The Empagliflozin and Intranasal Insulin Placebo group showed a mean change of 0.0 z-score (Standard Deviation: 0.2).
- The Intranasal Insulin and Empagliflozin group showed a mean change of 0.2 z-score (Standard Deviation: 0.2).
- The Placebo group showed a mean change of -0.1 z-score (Standard Deviation: 0.4).
For 'Change in the 14-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 14) Score':
- The Intranasal Insulin and Empagliflozin Placebo group showed a mean change of -0.5 score on a scale (Standard Deviation: 4.0).
- The Empagliflozin and Intranasal Insulin Placebo group showed a mean change of 1.0 score on a scale (Standard Deviation: 3.5).
- The Intranasal Insulin and Empagliflozin group showed a mean change of 2.0 score on a scale (Standard Deviation: 4.0).
- The Placebo group showed a mean change of 1.2 score on a scale (Standard Deviation: 4.6).
What this means
The results from this Phase 2 pilot study indicate that empagliflozin, both alone and in combination with intranasal insulin, was well-tolerated, with no treatment-related serious adverse events reported across any of the intervention groups. While the cognitive outcome measurements from this small pilot study showed varied changes, the favorable safety profile provides preliminary data for future research into these therapeutic approaches for mild cognitive impairment and Alzheimer's disease.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05081219, titled 'SNIFF - Combo INI+EMPA Trial,' were posted on 2025-10-21 on clinicaltrials.gov.