12-month effects of incretins versus SGLT2-Inhibitors on cognitive performance and metabolic profile. A randomized clinical trial in the elderly with Type-2 diabetes mellitus.

Aim: The aim of the present study is to examine the effects on cognitive performance, anthropometric measures, and metabolic markers in 2 different treatments: Incretins vs sodium-glucose co-transporter-2 inhibitors (SGLT2-I).

Materials and methods: A randomized controlled clinical trial was carried out on 39 elderly subjects (23 men and 16 women) with type 2 diabetes mellitus, with a mean age of 77.21±8.07 years. Body mass index (BMI) of 29.92±4.31 kg/m² and a cognitive status measured by a Mini Mental State Examination (scores >27 points). The subjects were on a 3-month treatment with a maximal dose of metformin as a stable regime, with the addition of incretins (liraglutide at doses of up to 1.8 mg/d; vildagliptin at 100 mg/d; sitagliptin 100 mg/d; and linagliptin 5 mg/d), or SGLT2-I (canagliflozin 300 mg/d; empagliflozin 25 mg/d; and dapagliflozin 10 mg/d). Glucose control was monitored by fasting glucose and glycosylated hemoglobin. Cognitive performance (by way of Verbal Fluency Test, Attentive Matrices Test, and Babcock Story Recall Test), anthropometric measures, and plasma lipids were also evaluated.

Results: Cognitive status did not change significantly during the 12 months of treatment in either group: Verbal Fluency Test: (SGLT2-I: P=1.00, incretins: P=0.598); Babcock Story Recall Test (SGLT2-I: P=0.391; incretins: P=0.351); and Attentive Matrices Test (SGLT2-I: P=0.679, incretins: P=0.901). SGLT2-I also resulted in a reduction in weight (-1.95 kg; P<0.05), in BMI (-0.69 kg/m²; P<0.05) and an increase in high-density lipoprotein cholesterol (+5.73 mg/dl; P<0.01).

Conclusion: Preliminary data show that patients treated with incretins and SGLT2-I have not suffered a reduction in cognitive performance during the 1 year of treatment. Metabolic outcome seemed to benefit, in particular, in patients who were treated with SGLT2-I.