Potential Impact of Choline Alphoscerate on Depressive Symptoms in Association with Insulin Resistance in Elderly Patients with Type 2 Diabetes

<b>Background/Objectives:</b> The aim of this study was to investigate whether Gliatamin (choline alphoscerate), an acetylcholine precursor originally used to treat dementia, improves depressive symptoms in patients with type 2 diabetes. <b>Methods:</b> We conducted a 6-month double-blind, randomized, and placebo-controlled trial involving 49 participants with type 2 diabetes, older than 50 years, and with mild depressive symptoms; 33 and 16 participants received choline alphoscerate (800 mg/day) and a placebo, respectively. <b>Results:</b> At 6 months, the Hamilton Depression Rating Scale was significantly decreased in both the choline alphoscerate (15.9 ± 6.5 to 12.6 ± 5.8, <i>p</i> = 0.001) and placebo (15.4 ± 4.7 to 10.2 ± 3.9, <i>p</i> = 0.004) groups compared with baseline, without inter-group difference (<i>p</i> = 0.297). Meanwhile, the choline alphoscerate group showed favorable results in insulin resistance-related parameters at 6 months, including the waist circumference (WC) and the low-density lipoprotein cholesterol (LDL)/high-density lipoprotein cholesterol (HDL) ratio (<i>p</i> for inter-group difference vs. placebo = 0.009 and 0.092). Even after adjusting for multiple confounding factors, choline alphoscerate use was associated with an increased odds for reduction in WC (OR 18.28 [95% CI 2.27-461.35]) and a decreased odds for a high LDL/HDL ratio at 6 months (OR 0.16 [95% CI 0.03-0.76]). <b>Conclusions:</b> Choline alphoscerate did not show superiority over the placebo in terms of the alleviation of depressive symptoms, despite significant pre-post changes observed within the choline alphoscerate group. Nevertheless, given its positive potential for insulin resistance, the effects of choline alphoscerate on depressive mood in relation to insulin resistance in patients with type 2 diabetes require further validation.