Antidepressant fluoxetine improves glucose metabolism in diabetics, systematic review.

There has been rising concern about metabolic effects of antidepressants with emerging data on antecedent risk of increasing risk of diabetes, obesity and cardiovascular diseases. No conclusive evidence is available for the metabolic risk profile of fluoxetine in this regard. A recent systematic review by Zizhen Zhang et al has found that Fluoxetine has beneficial effects on improving glucose metabolism in diabetic patients.

Fluoxetine is FDA-approved for major depressive disorder, obsessive compulsive disorder, panic disorder and bulimia. Although it has not been approved for weight loss, the effect has been widely considered. It has been found superior to other anti-depressants in terms of safety and efficacy.

In the present systematic review, the database for the effects of fluoxetine on glucose and lipid metabolism were collected from 24 studies. The main outcome measures were fasting blood glucose, glycosylated hemoglobin (mainly HbA1c) and body weight.

The metabolic status of the participants was different at baseline between the

included studies and could be divided into the following categories according to the metabolic status of the participants: T2DM with obesity, T2DM with depression, T1DM, T1DM or T2DM, patients with depression, simple obesity volunteers and healthy volunteers.

The dose of fluoxetine was fixed at 60 mg/day in 10 RCTs, 20 mg/day in three RCTs, and 40 mg/day in one RCT; seven studies were randomized (20–80 mg/day). The course of treatment ranged from 4 weeks to 1 year.

The meta-analysis showed that FBG and HbA 1c levels were moderately decreased and body weight was significantly decreased with fluoxetine treatment compared with placebo.

Both plasma triglyceride (TG) and total cholesterol (TC) levels were also decreased significantly. There was not much change found in respect to HDL. In regards LDL some studies found it to be significantly reduced, while the others found no change in LDL levels.

What's the mechanism of this benefit?

First, the biochemical changes in the serotonin pathway induced by fluoxetine directly lead to a change in glucose efficiency. Serotonin also stimulate insulin secretion by directly acting on pancreatic β-cells, reducing insulin resistance, and improving insulin sensitivity and weight loss.

Second, remission of depressive symptoms not only indicates glycemic control but also improves compliance with antidiabetic drugs.

It has been suggested that the serotonergic pathway is associated with the development of symptoms during hypoglycemia in people, whether healthy people or patients with T1DM.

During hypoglycemia, fluoxetine can amplify the autonomic nerve glucose metabolism counterregulatory response and is a potentially important defensive measure to prevent hypoglycemia.

These studies also suggest that fluoxetine can also improve the blood lipid profile and is good for reducing the occurrence of cardiovascular and cerebrovascular events if diabetes patients are complicated with this disease.

To summarise, this systematic review found that fluoxetine had a positive effect on improving blood glucose control in patients with disorders of glucose metabolism and was good for weight management in obese people despite significant heterogeneity between studies.

Source: Asian Journal of Psychiatry

https://doi.org/10.1016/j.ajp.2022.103092