Drugs Affecting Body Weight and Fat Distribution

DRUGS AFFECTING BODY WEIGHT AND FAT DISTRIBUTION
Drug class	Examples	Average weight gain (per year)	Notes
WEIGHT GAIN EFFECT
Antidiabetics
Insulin	insulin aspart, insulin glulisine, insulin lispro, insulin regular		• More pronounced in regimens with rapid-acting insulin compared to basal insulin only • Regimens with metformin reduce the weight gain effect
Sulfonylureas	glimepiride, glipizide, glyburide	~4kg	More pronounced in the 1^st months, then reaches a plateau
Thiazolidinediones	pioglitazone, rosiglitazone	1.5–4kg	Almost entirely only subcutaneous fat accumulation
Antihypertensives
Beta-blockers	atenolol, metoprolol, propranolol	1–4kg	• More pronounced in the 1st few months, then no further weight gain • Select vasodilating beta-blockers (eg, nebivolol, labetalol, carvedilol) in patients with high risk for metabolic effects
Psychotropics¹
Anticonvulsants	lamotrigine, levetiracetam, tiagabine, oxcarbazepine	<1kg	• Most prominent with valproate and carbamazepine • Valproate induces weight gain in 71% of patients, with most weight gain observed within 1st year. Females, post-pubertal adolescents, and those overweight at baseline are the most susceptible. Weight gain is not dose- or serum level-related. • Carbamazepine induces weight gain in 43% of patients
	gabapentin, pregabalin	1–5kg
	valproate, carbamazepine	>5kg
Antipsychotics (atypical)^2,3	aripiprazole, ziprasidone, lurasidone, paliperidone, iloperidone, asenapine	<1kg	• More pronounced in patients with normal baseline body weight and in females • More significant weight gain in drug-naïve patients vs previously exposed (more in children vs adults) • Weight gain is time- and dose-dependent, and can be predicted by increases in the first weeks of treatment
	quetiapine, risperidone	1–5kg
	clozapine, olanzapine	>5kg
Antipsychotics (typical)²	haloperidol, perphenazine	1–5kg
MAOIs	phenelzine	1–5kg
Mood stabilizers	lithium	>5kg	• Significant weight gain (>5% of initial body weight) occurs in majority of patients • Risk factors: females, high baseline weight, younger age, concomitant antidepressants
SNRIs⁶	duloxetine, venlafaxine	<1kg	Weight gain with chronic therapy
SSRIs⁶	escitalopram	<1kg	• Weight gain with chronic therapy • Greatest long-term weight gain with paroxetine
SSRIs⁶	paroxetine, citalopram, fluoxetine, sertraline	1–5kg
Tricyclic antidepressants (TCAs)	amitriptyline, nortriptyline, imipramine, desipramine, doxepine, clomipramine	1–5kg	Greatest with amitriptyline and nortriptyline
Other antidepressants	trazodone⁶, nefazodone	<1kg
Other antidepressants	mirtazapine⁶, maprotiline	1–5kg
WEIGHT GAIN AND LIPODYSTROPHY EFFECT
Antiretrovirals⁴
Integrase inhibitors	raltegravir, dolutegravir		• Associated with lipohypertrophy (central/truncal fat accumulation) or weight gain • A switch from NRTI, NNRTI or PIs to integrase inhibitors may cause even greater weight gain
NRTIs	didanosine, lamivudine, stavudine, zidovudine		• Lipoatrophy (loss of subcutaneous fat) greatest with NRTIs stavudine and zidovudine • Lipoatrophy risk factors: males, older age, lower baseline weight, lower CD4 count, higher baseline viral load, hepatitis C co-infection • Lipohypertrophy is not antiretroviral-specific; does not reverse on switching antiretrovirals • Lipohypertrophy risk factors: females, older age, baseline weight, diet, longer treatment duration • PIs are more associated with lipo-accumulation and metabolic effects • Older PIs (eg, indinavir, lopinavir, ritonavir) are associated with threefold increase in diabetes risk • Newer PIs show neutral effects on peripheral lipoatrophy and conflicting effects on central lipohypertrophy • A switch from NRTI and NNRTI to PIs showed no changes in weight
NNRTIs	delavirdine, efavirenz, etrivirine, nevirapine, rilpivirine
Protease inhibitors (PIs)	amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir, fosamprenavir
Glucocorticoids
Corticosteroids	prednisone, dexamethasone, methylprednisolone	>10kg in ~20% of patients	• Weight gain significantly increases with doses >5mg/day prednisone or equivalent • Recent data showed that higher doses of inhaled corticosteroid is associated with BMI increases in children with asthma compared to those with steroid-free treatments • Lipodystrophy greater in females, younger patients, and higher baseline BMI
NOTES
Key: BMI = body mass index; MAOIs = monoamine oxidase inhibitors; NRTIs = nucleoside/nucleotide reverse transcriptase inhibitors; NNRTIs = non-nucleoside reverse transcriptase inhibitors; SNRI = serotonin and norepinephrine reuptake inhibitors; SSRI = selective serotonin reuptake inhibitors ¹ Monitor weight before and shortly after initiation of psychotropic drugs. Reconsider therapeutic options or initiate weight-controlling strategies if a 5% increase above baseline weight occurs after the first month of treatment. ² Up to 80% of patients on antipsychotics experience weight gain that exceeds their ideal body weight by ≥20%. ³ The American Diabetes Association and American Psychiatric Association (ADA/APA) Consensus Development Conference recommends close monitoring of weight and metabolic and cardiovascular risk factors in all patients taking atypical antipsychotics. Switch to other antipsychotic with less potential for weight and cardiometabolic effects if >5% weight gain or worsening of lipid or glycemia parameters. ⁴ Patients on HAART have greater cardiometabolic risk due to weight gain compared to non-HIV patients. Weight gain is most pronounced in low baseline weight, high viral load, and low WBC. Monitor changes in body composition using BMI, waist circumference, waist-to-hip ratio, and screen regularly for clinical lipodystrophy in all HIV patients at diagnosis, prior to HAART initiation, and annually thereafter. ⁵ Not associated with increased inflammation or fibrosis unlike in NAFLD. ⁶ According to recent long-term prospective data, most weight gain is associated with mirtazapine, fluoxetine, citalopram, escitalopram, sertraline, paroxetine, trazodone, venlafaxine, and duloxetine, in contrast to older data where TCAs had the highest.
REFERENCES
Verhaegen AA, Van Gaal LF. Drugs Affecting Body Weight, Body Fat Distribution, and Metabolic Function-Mechanisms and Possible Therapeutic or Preventive Measures: an Update. Curr Obes Rep. 2021 Mar;10(1):1-13. doi: 10.1007/s13679-020-00419-5 (Rev. 4/2024)

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