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AboEl-Azm et al. | Journal of Clinical and Translational Research 2023; 9(4): 222-235 227
Table 1. (Continued)
Study ID Design Country Duration Patient’s eligibility Type of insulin Outcomes measured Main finding
(months)
Reger RCT United States NR • There were no - Novolin R containing Primary: Intranasal
et al. [19] neurological cresol, Novo Nordisk, • Cognitive data, such as (verbal insulin improves
disorders (other than Princeton, NJ, USA memory for story recall) AD
AD) Secondary:
• Plasma insulin
• Blood glucose levels
• Attention,
• Working memory
• Negative effects such as
(nosebleed – nose soreness)
Abbreviations: Apo e4: Apolipoprotein E4; DSRS: Dementia Severity Rating Scale; ADAS-cog: Alzheimer Disease’s Assessment Scale-cognitive subscale; ADCS-ADL: Alzheimer’s Disease
Cooperative Study–activities of daily living; CDR-SOB: Clinical Dimension Rating–Sum of Boxes; MMSE: Mini-Mental State Examination; NR: Not reported; AD: Alzheimer’s disease;
MCI: Mild cognitive impairment; CSF: Cerebral spinal fluid; COWAT: Controlled Oral Word Association Test; WMS-IV: Wechsler Memory Scale

3.3.5. Memory composite (delayed story recall) long-acting either of the two groups in terms of ADCS-ADL 20 IU. The MD
was 0.02 (95% CI: −0.09 – 0.13, P = 0.72). The results were
Two studies provided adequate data for memory composite homogenous (I = 0%, P = 0.59) (Figure 4D).
2
long-acting involving 63 participants. We found no significant
difference between the intranasal insulin and the placebo. The 3.3.11. Clinical Dementia Rating-Sum of Boxes score
MD was 0.58 (95% CI: −0.04 – 1.19, P = 0.07). The results were Two studies provided relevant data for clinical dimension
homogenous (I = 0%, P = 0.71) (Figure 3E).
2
rating – the sum of boxes involving 268 participants. We did
3.3.6. DSRS 40 IU not find a significant difference between the two groups. The
MD was 0.36 (95% CI: −0.19 – 0.92, P = 0.2). The results were
Three studies reported relevant data for DSRS 40 IU with a homogenous (I = 0%, P = 0.54) (Figure 4E).
2
total of 160 participants. The overall effect did not favor either of
the two groups in terms of DSRS 40 IU. The MD was −0.15 (95% 3.3.12. CSF biomarkers of AD
CI: −0.88 – 0.57, P = 0.68). The findings of the studies were We found a non-significance difference between the intranasal
homogenous (I = 0%, P = 0.6) (Figure 3F).
2
insulin and the placebo in the case of CSF biomarkers of AD. The
3.3.7. DSRS 20 IU MD was −3.23 (95% CI: −9.9 – 3.44, P = 0.34). In addition, the
overall effect did not favor either of the two groups in terms of
Regarding DSRS 20 IU, we identified two relevant studies with Abeta42, Tau, and Tau-P. More information is given in Figure 5.
a total of 132 participants. There was no significant difference
between the two groups. The MD was −0.11 (95% CI: −0.82 – 3.3.13. Adverse effects
0.6, P = 0.76). The pooled articles were homogenous (I = 0%, We categorized data into three subgroups (Headache, Rhinitis/
2
P = 0.59) (Figure 4A). URI, and Fall) involving 1001 participants. The findings of
3.3.8. DSRS-LA overall adverse events and the subgroups revealed no significant
difference between the two groups. The RR of overall adverse
Two studies provided relevant data for DSRS-LA with a total events was 1.28 (95% CI: 0.75 – 2.21, P = 0.36). All details are
of 63 participants. The overall effect did not favor either of the two in Figure 6.
groups in terms of DSRS-LA. The MD was 0.16 (95% CI: −3.98 –
4.29, P = 0.94). The results were homogenous (I = 0%, P = 0.85) 4. Discussion
2
(Figure 4B) The introduction of effective medicine for several CNS-related
3.3.9. ADCS-ADL 40 IU disorders, including AD, by nose-to-brain drug administration,
has been considered a revolutionary process [21]. Intranasal
We identified three studies that reported relevant data for ADCS- insulin is one of these treatments that have shown a beneficial
ADL 40 IU involving a total of 376 participants. The overall effect impact on AD patients [11]. In the present study, 12 RCTs were
did not favor either of the two groups in terms of ADCS-ADL included in the study. All the included studies retrieved from our
40 IU. The MD was 0.04 (95% CI: −0.07 – 0.15, P = 0.49). The literature search compared intranasal insulin with placebo in terms
pooled studies were homogenous (I = 0%, P = 0.58) (Figure 4C). of safety and efficacy. The duration of treatment in the included
2
3.3.10. ADCS-ADL 20 IU studies ranged from 4 months to 4 years. The findings of our
meta-analysis revealed that intranasal insulin might be significant
Two studies provided adequate data for ADCS-ADL 20 IU in improving cognition in Alzheimer’s disease patients measured
with a total of 132 participants. The overall effect did not favor by ADAS-cog with lower doses being more effective. There was
DOI: http://dx.doi.org/10.18053/jctres.09.202304.23-00013