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Metformin effective against antipsychotic-induced dyslipidemia

Metformin treatment had a significant effect on antipsychotic-induced adverse metabolic effects, including dyslipidemia at 24 weeks and insulin resistance at 12 weeks, according to data published in Molecular Psychiatry.

“A large body of literature shows that antipsychotics, particularly atypical antipsychotics, cause serious adverse metabolic effects, which include dyslipidemia, weight gain, insulin resistance and glucose intolerance,” Ren-Rong Wu, MD, of the Mental Health Institute of the Second Xiangya Hospital, National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, at Central South University, in Changsha, China, and colleagues wrote. “ … Dyslipidemia has become a major concern in the treatment of psychosis. However, there is a relative lack of interventions to control antipsychotic-induced dyslipidemia.”

To analyze the effect metformin treatment has on antipsychotic-induced dyslipidemia, and examine insulin resistance in treatment-related changes in lipid profile in patients with schizophrenia, the researchers pooled data from two, randomized, placebo-controlled studies. The studies, conducted at the Mental Health Institute of the Second Xiangya Hospital, Central South University, were initially intended to examine the efficacy of metformin in treating antipsychotic-induced metabolic effects, including weight gain.

In the two studies, 201 patients with schizophrenia who developed dyslipidemia following antipsychotic treatment were randomly assigned to take either 1,000 mg of metformin per day, or a placebo, for 24 weeks. Evaluations were conducted at baseline, 12 weeks and 24 weeks. The primary outcome was the LDL cholesterol levels.

According to the researchers, the mean difference in the LDL levels between the metformin and placebo groups was from 0.16 mmol/L^-1 at baseline to –0.86 mmol/L^-1 at week 24. In addition, 25.3% of patients in the metformin group had a LDL level of 3.37 mmol/L^-1 or greater, compared with 64.8% in the placebo group, at week 24. The researchers also observed that, compared with the placebo, metformin treatment also had a significant effect on reducing body weight, BMI, insulin, insulin resistance index, total cholesterol and triglyceride. It also increased HDL cholesterol levels. According to the researchers, metformin’s effects on weight and insulin resistance appeared at week 12 and were further improved by week 24. The treatments effects on dyslipidemia only significantly appeared at 24 weeks.

“After a 24-week trial, we found that metformin treatment had significant effect on not only controlling weight gain, insulin and insulin resistance, which is consistent with our previous studies, but also significantly improving the altered level of lipids, including LDL, HDL, total cholesterol and triglycerides in blood,” Wu and colleagues wrote. “These effects on insulin and lipids were in a time-sequence manner, and improvement of lipid profile was at least partly independent of reducing insulin resistance.” – by Jason Laday