Consider Metformin to Prevent Weight Gain From Antipsychotics

You’ll see more focus on using metformin to prevent antipsychotic-induced weight gain (AIWG)...due to new guidelines.

Up to 8 in 10 people with severe mental illness seem to gain at least 7% of their body weight within a year of starting an antipsychotic.

And weight gain carries risks such as diabetes...cardiovascular disease...and significant distress leading to poor medication adherence.

Continue to counsel about moderate exercise and limiting fatty or high-calorie foods...to encourage a healthy lifestyle.

Use these tips when considering metformin for AIWG in patients starting or continuing an antipsychotic.

Why use metformin for weight loss? Explain to patients that it helps reduce appetite, limit glucose production, and improve insulin response...plus it’s low cost.

Patients who take metformin alongside an antipsychotic for schizophrenia seem to gain about 3 to 5 kg less weight compared to those who aren’t taking metformin...over an average of 12 weeks.

When should metformin be used to prevent AIWG? Consider starting metformin with any antipsychotic with a high risk of weight gain, such as clozapine or olanzapine.

Also suggest metformin with antipsychotics with a moderate risk of weight gain (risperidone, etc) if the patient also has one or more CV risk factors (hypertension, etc).

And consider metformin for patients on any antipsychotic if they gain more than 3% of their baseline weight in the first year.

If appropriate, suggest starting or switching to an antipsychotic with a lower risk of weight gain, such as aripiprazole or ziprasidone.

Lean away from metformin in patients who are currently overweight or obese...instead consider GLP-1 agonists (semaglutide, etc), since these lead to more weight loss than metformin.

How should metformin be dosed for AIWG? Recommend 500 mg daily and increase to 500 mg bid after one week, then increase by 500 mg every 2 weeks up to 1-2 g/day, as tolerated.

Advise monitoring kidney function at least annually, or more often if needed, such as in patients who also have hypertension.

Limit metformin to 1 g/day for patients with an eGFR of 30 to 44 mL/min...to reduce the risk of lactic acidosis...and avoid it if the eGFR is below 30.

How long should metformin be continued? There’s no good evidence to guide how long to continue metformin. But advise continuing for the duration of antipsychotic use...since it’s likely that their appetite will return and all or some of the weight may be regained if it’s stopped.

But recommend stopping metformin if their BMI falls below 20.

Explore our chart, Comparison of Atypical Antipsychotics, for more on weight gain risks and other side effects.

• Chart: Comparison of Atypical Antipsychotics (Canada)