Usefulness of Fluoxetine in Obese Non‐Insulin‐Dependent Diabetics: A Multicenter Study

Abstract

Weight reduction is essential in the management of most noninsulin‐dependent diabetics, but this therapeutical goal is difficult to obtain. In this double‐blind parallel study, 82 noninsulin‐dependent diabetics, moderately obese (BMI = 30–39 kg/nr2), were given for an 8‐week period either placebo (P) or fluoxetine (F), a specific serotonin reuptake inhibitor, in addition to their usual antidiabetic treatment. Thirty‐nine of them received 60 mg fluoxetine a day and 43 were given the placebo. At admission, both groups had similar weight excess, metabolic control and serum lipid values. In comparison with the P‐treated subjects, those treated with fluoxetine (F) lost more weight after 3 weeks (‐1.9 vs. −0.7 kg, p<0.0009) and after 8 weeks (‐3.1 vs. −0.9 kg, p<0.0007). Fasting blood glucose decreased in group F after 3 weeks (‐ 1.5 vs. −0.4 mmol/L, p<0.003) and after 8 weeks (‐1.7 vs. −0.02 mmol/L, p<0.0004). HbAlc decreased from 8.5% to 7.7% in group F and from 8.6% to 8.3% in group P (p=0.057). Mean triglyceride level was also reduced in group F after 8 weeks (p=0.042). Fasting C‐pep‐tide did not change in either group, but fasting insulin values decreased in group F after 3 weeks (p<0.02) and after 8 weeks (p<0.05). The insulin/C‐peptide molar ratio decreased significantly in group F after 3 weeks (p<0.04) and after 8 weeks (p<0.05) in comparison with group P. The drug was generally well tolerated and no major side effects were reported. In conclusion, the addition of fluoxetine to the usual oral hypoglycemic agent therapy might be beneficial in obese non‐insulin‐dependent diabetics, at least on a short‐term basis.

Human Beta Cells Produce and Release Serotonin to Inhibit Glucagon Secretion from Alpha Cells

“…While the hypoglycemic effects of SSRIs have been proposed to be beneficial for diabetic patients (Daubresse et al, 1996), SSRIs may also render diabetic patients susceptible to life-threatening hypoglycemia. Indeed, patients on long-term SSRI treatment have poor counter-regulatory responses (Biagetti and Corcoy, 2013; Deeg and Lipkin, 1996; Derijks et al, 2008; Sawka et al, 2000, 2001; Takhar and Williamson, 1999).…”

Lower Central Serotonergic Responsivity Is Associated With Preclinical Carotid Artery Atherosclerosis

“…9,31,32 The current study findings suggest partial mediation by the metabolic syndrome and, in this regard, several clinical trials have examined the effects of SSRI treatment on glucose metabolism in individuals with type 2 diabetes, impaired glucose tolerance, or obesity. Though not uniform, trial findings include lowered fasting blood glucose or glycosylated hemoglobin with SSRI treatment, 33,34 improved insulin sensitivity assessed by euglycemic clamp, 35 reduced hepatic glucose production, and enhanced peripheral glucose uptake. 36 Moreover, preliminary data from pharmacoepidemiologic investigations and randomized clinical trials suggests that treatment of depression with SSRIs may reduce major heart disease events.…”

Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats

“…However, it is recognized that fluoxetine increases insulin receptor sensitivity (31) and competes with sulfonylurea for cytochrome P-450 metabolism (29), requiring adjustment of the doses of insulin or hypoglycemic agents to avoid hypoglycemia (32,33). On the other hand, non-insulin-dependent diabetic patients who are treated with fluoxetine show a consistent reduction in carbohydrate consumption and weight loss associated with a decrease in HbA1c (34,35). Ultimately, sertraline may be a better agent for depression treatment in diabetic patients (36).…”