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Clinical Research

Liraglutide improves memory in obese patients with prediabetes or early type 2 diabetes: a randomized, controlled study

Abstract

Background/objectives

Diabetic subjects are at increased risk of subtle cognitive impairment since the disease early stages and of dementia later in life. In animal models, glucagon-like peptide-1 receptor agonizts (GLP1-RAs) have been shown to exert neuroprotective effects, expecially in the memory domain. We assessed whether treatment with a GLP1-RA might affect cognitive functions in type 2 diabetic subjects independently on the weight loss it might induce.

Subjects/methods

Forty metformin-treated obese subjects with prediabetes or newly diagnosed type 2 diabetes mellitus, received liraglutide (1.8 mg/d) (n = 20) or lifestyle counseling (dietary intervention and exercise training) (n = 20) until achieving a modest and comparable weight loss (−7% of initial body weight).

Interventions/methods

A detailed neuropsychological assessment before and after weight loss was completed in 16 patients per arm, who were administered a total of seven psychological tests, thus assessing three composite domain z-scores for attention, memory, and executive control.

Results

After comparable weight loss and superimposable glycemic control and insulin sensitivity, a significant increase in short term memory (mean Digit Span Z score from −0.06 to 0.80, p = 0.024) and memory composite z-score (mean memory z-score from −0.67 to 0.032, p = 0.0065) was observed in the liraglutide exposed subjects (between group p = 0.041 and p = 0.033, respectively).

Conclusions

Liraglutide might slow down memory function decline in diabetic patients in early, and possibly preclinical stages of the disease.

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Fig. 1: Effects of liraglutide- or lifestyle-induced weight loss on short-term memory, composite memory domain, selective attention and composite attention domain, in obese subjects with prediabetes or early type 2 diabetes mellitus.
Fig. 2: Correlation between time-to-weight-loss and change in short term memory or in the composite memory-domain throughout the treatment period in the liraglutide and lifestyle arms.

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Acknowledgements

We thank Prof Riccardo Bonadonna and Dr Maria Linda Boselli for their contribution in the analysis of the data; for education in the lifestyle arm; Dr Ermanno Angelucci for patients’ recruitment; Drs Marika Leo, Alessia Quirino, and Gabriella Bosco for patients education; Dr Matteo Polimene and Maria Pia Baldassare for help in the neuropsychological data management.

Funding

This study was supported by a grant from the Italian Ministry of University and Research (PRIN no. 2010JS3PMZ to FS).

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Contributions

FV, PGS, and FS contributed to the study design and protocol, the analysis plan, the supervision of the analysis, study implementation, data acquisition and interpretation, statistical analyses, writing of the manuscript, and critical revision and final approval of the manuscript. PGS and AB contributed to study implementation, data acquisition and interpretation, and writing of the manuscript. MTG, FC, RL, and RT contributed to study implementation, data acquisition and interpretation, and final approval of the manuscript. ADC contributed to statistical analysis and data interpretation. AC contributed to the supervision of the analysis, data interpretation, writing of the manuscript, and critical revision and final approval of the manuscript. FS, FV, and AC are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Francesca Santilli.

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Conflict of interest

AC received lecture fees and fees for serving on advisory boards from Novo Nordisk, Eli Lilly, AstraZeneca, Sanofi Aventis, Merck Sharp & Dohme, and Takeda; and grant support to his institution from Novo Nordisk. No other potential conflicts of interest relevant to this article were reported.

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Vadini, F., Simeone, P.G., Boccatonda, A. et al. Liraglutide improves memory in obese patients with prediabetes or early type 2 diabetes: a randomized, controlled study. Int J Obes 44, 1254–1263 (2020). https://doi.org/10.1038/s41366-020-0535-5

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