Which Drugs Cause Weight Gain?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on May 7, 2024.

Some common medicines that may cause weight gain include some type 2 diabetes drugs like insulin or glyburide (Diabeta), certain antidepressants such as amitriptyline or paroxetine (Paxil), antipsychotic medicines like clozapine (Clozaril), some antihistamines like diphenhydramine (Benadryl) and corticosteroid drugs like prednisone.

Losing weight, or maintaining a healthy weight, can be a battle for many patients. Aging, lack of exercise, and food choices are all culprits in the battle to keep weight down. But medicines can cause weight gain too, and in some cases may require a change in therapy.

15 Common Medicines That Cause Weight Gain

• Actos (pioglitazone) - type 2 diabetes
• Allegra (fexofenadine) - antihistamine
• Amitriptyline - a tricyclic antidepressant
• Anafranil (clomipramine) - a TCA antidepressant (obsessive compulsive disorder)
• Benadryl (diphenhydramine) - antihistamine
• Clozaril (clozapine)- an antipsychotic
• Depo-Provera (medroxyprogesterone) - birth control shot
• Diabeta (glyburide) - type 2 diabetes
• Insulin analogs - Novolog, Lantus, Humalog
• Lithobid (lithium) - mood stabilizer
• Neurontin (gabapentin) - anticonvulsant (to treat seizures), used for nerve pain
• Paxil (paroxetine) - an SSRI antidepressant
• Prednisone - a corticosteroid
• Remeron (mirtazapine) - an antidepressant
• Tenormin (atenolol) - beta blocker; lowers blood pressure, treats angina (chest pain)

Learn More: Check to see if your medicine causes weight gain

Why do medicines cause weight gain?

If you are taking a prescribed medication for a medical condition, and it's causing weight gain, that almost seems unfair. Diabetes drugs, antidepressants, antihistamines and even some pain medications can all increase weight. So why does this happen?

To start, many common medical conditions are treated with medicines that are well known to lead to weight gain. These include health conditions like schizophrenia, depression, obsessive compulsive disorder (OCD), bipolar disorder, diabetes, high blood pressure, epilepsy / seizures, allergies, and pain and inflammation.

Some medications cause weight gain more commonly than others, and not all patients will experience weight gain as a side effect. But it's important to understand your risk for added weight and what you can do to prevent it.

Medicine side effects that may result in weight gain:

• increased appetite
• fluid (water) retention
• elevated fat storage
• a slowed metabolism
• fatigue, lethargy or weakness (leading to less exercise / activity)

For many drugs, it is not known exactly what causes weight gain. Weight gain is usually a slow process. It is often difficult to distinguish between weight gain from a drug and weight gain from other reasons, like diet or lack of exercise. Plus, some conditions, like depression, can lead to weight loss or weight gain, depending upon the individual.

However, if a rapid weight gain or rapid fluid retention occurs in a short period of time, contact your healthcare provider right away. If you are at risk for heart or lung disease, chronic heart failure or high blood pressure, rapid weight gain can be a sign of fluid retention or other problems.

What problems occur from drug-related weight gain?

Being overweight can result in several common health problems:

• prediabetes
• type 1 or type 2 diabetes
• osteoarthritis
• high blood pressure (hypertension)
• high cholesterol
• metabolic syndrome - excess body fat in the waist, high blood pressure, high blood sugar, and high cholesterol (lipid) levels
• heart disease or stroke
• cancer
• sleep apnea or other respiratory diseases
• fatty liver disease
• kidney disease
• pregnancy problems

Is my medicine causing weight gain?

If you have started a new medication in the last 6 months to a year, and put on more than a few pounds, think about ways this might have happened:

• Have you been eating more calories, either in the types of food you eat or the amount of food you eat?
• What about your salt intake? Are you seeing swollen ankles due to fluid retnetion?
• Did you change the amount of daily activity you do, such as reduced exercising or more sitting at a desk or computer?
• Have you had a significant change or stressor in your life that may have lead to overeating?
• Did you start a new medication regimen that may be causing weight gain as a side effect?

Ask your healthcare provider about the potential for weight gain before you start a new medication. Are there alternatives that do not have weight gain as a side effect? And remember, medications can affect patients differently, and not everyone will gain weight. 

How is medication-related weight gain treated?

• Do not stop taking any medication without talking to your doctor first. If you have a concern about weight gain with a medicine, make an appointment to discuss your concerns.
• In many cases, you may be able to switch to a different medication, use a lower dose, or change drug class. Together, you and your doctor can make sure the benefits of the medicine outweigh the risks from any weight gain.
• You may need to have a multi-faceted approach too: an increase in daily exercise, attention to diet, and limiting salt intake may be recommended. Limiting portion sizes, drinking plenty of water throughout the day, and eating slowly are other tips.

Newer weight-loss treatments, such as the GLP-1 agonists or a GIP / GLP-1 receptor agonist, may be an option for weight loss in patients with heart disease and overweight or obesity and that may be associated with a cardiovascular risk factor, like high blood pressure, high cholesterol or type 2 diabetes. These agents are not specifically approved to treat medication-related weight gain. 

GLP-1 agonists are used to maintain long-term weight loss along with a reduced calorie diet. Some are specifically approved to treat type 2 diabetes only, but might be prescribed off-label for weight loss maintenance. There are various brands and they come as daily or weekly subcutaneous injections or as an oral tablet taken once per day.

GLP-1 agonists include:

• Mounjaro (tirzepatide injection)
• Ozempic (semaglutide injection)
• Rybelsus (semaglutide oral tablet)
• Saxeda, Victoza (liraglutide injection)
• Wegovy (semaglutide injection)
• Zepbound (tirzepatide injection)

If you do gain a few pounds with a new medicine, don't let it affect your self-esteem. The weight may come off with added daily exercise, a change in eating habits, or a change in drug treatment - but only do so under your doctor's advice.

Learn more: Obesity and Weight Loss Resource Center

Drugs and drug classes that cause weight gain

Here are some common drugs and drug classes that may lead to weight gain. Many medications cannot be changed or stopped, so follow your healthcare provider's advice. This is not a complete lists of drugs that might lead to weight gain, so if you have concerns, talk to your doctor.

1. Antidepressants

Usually, a physician can choose among many alternatives in the antidepressant class if weight gain is an issue. Some antidepressants may lead to weight gain by interfering with the serotonin neurotransmitter serotonin that controls appetite. Others can elevate antihistamine effects and appetite, or may cause sedation and fatigue that lowers your level of exercise or other activity.

Weight gain

Older antidepressants, known as tricyclic antidepressants (TCAs) are notorious for increasing appetite and for causing weight gain.

TCAs affect neurotransmitters in the brain and also exhibit antihistamine activity, which can boost appetite. TCAs are also used to treat migraine headaches, anxiety, insomnia, and other conditions.

Examples of TCAs that can commonly lead to weight gain are:

• amitriptyline
• trimipramine (Surmontil)
• imipramine (Tofranil)
• doxepin (Silenor)

Clomipramine (Anafranil) can also lead to weight gain, but it is approved for treatment of obsessive-compulsive disorder (OCD).

Another commonly used class of antidepressants, the selective serotonin reuptake inhibitors (SSRIs), are not always associated with weight gain. However, some frequently prescribed SSRIs, like paroxetine (Paxil) or fluvoxamine (Luvox) can cause this side effect.

Mirtazapine (Remeron) is an atypical antidepressant that boosts serotonin, like SSRIs, but also has an antihistamine effect that may boost appetite and lead to significant weight gain.

In mirtazapine clinical studies, weight gain was reported in 12% of adults (with a weight gain of more than 7% reported in 8% of adults) and in half of pediatric patients. Increased serum cholesterol (15%) was also documented.

Monoamine oxidase inhibitors (MAOIs), an older class of antidepressant not frequently prescribed anymore, are not linked with significant weight gain.

Of the antidepressant MAOI class, phenelzine (Nardil) may be the most likely to lead to an increase in weight (in 1% to 10% of patients).

Rasagiline (Azilect) and selegiline (Eldepryl, Zelapar) are anti-parkinson disease MAOI agents that are not used for depression. They may commonly lead to weight loss in 1% to 10% of patients.

Weight loss, neutral or slight weight gain

Bupropion (Wellbutrin SR) is an antidepressant that is actually associated with weight loss; it's also linked with less sexual side effects than some other antidepressants like the SSRIs.

Venlafaxine (Effexor XR) and duloxetine (Cymbalta) are classified as selective serotonin and norepinephrine reuptake inhibitors (SNRIs) and have more neutral effects on weight gain. Other SNRIs also have a lesser effect on weight gain compared to TCAs or even SSRIs.

Vortioxetine (Trintellix) is an SSRI / serotonin modulator that had no significant effect on body weight as measured by the mean change from baseline in either short-term or longer-term (6 month) research trials looking at weight gain. However, some reports have been received of weight gain since approval, so discuss this side effect further with your doctor.

Trintellix is less likely to cause weight gain than older antidepressants such as the tricyclic antidepressants.

Other serotonin modulators such as nefazodone, trazodone (Desyrel), or vilazodone (Viibryd) also have a limited effect on weight gain.

Some SSRIs are also more weight neutral or may lead to moderate weight loss in the first 6 months.

SSRIs that may lead to lower weight gain include: fluoxetine (Prozac), citalopram (Celexa), escitalopram (Lexapro), or sertraline (Zoloft). For some people, the weight loss with these medicines at the outset may be temporary (possibly due to stomach side effects, for example, with Zoloft), and weight gain may occur 6 months to one year later in therapy.

2. Antihistamines

Antihistamines are commonly used to treat conditions such as allergic rhinitis (hay fever), cold or flu symptoms, food allergies, hives (urticaria), drug allergies, and insect bites or stings. Newer antihistamines usually cause less drowsiness than the 1st generation medicines, and are usually preferred to help prevent seasonal hay fever, animal dander allergies, and eye allergies to pollen.

Newer 2nd generation antihistamines, such as cetirizine (Zyrtec), loratadine (Claritin, Alavert) and fexofenadine (Allegra) selectively antagonize histamine H1 receptors.

• These drugs, which are available OTC without a prescription, have been associated with weight gain. Blocking histamine activity can boost appetite, as noted with several other drugs that cause weight gain.
• A study compared the use of antihistamines and the risk of obesity. Users of cetirizine (Zyrtec) and fexofenadine (Allegra) had significantly greater weight, body mass index (BMI), waist circumference, and insulin levels.
• Cetirizine (Zyrtec) can also lead to drowsiness in roughly 10% of patients, more than many other 2nd generation antihistamines.

Cyproheptadine, an older H1 antihistamine, has actually been used to increase weight gain in patients with chronic diseases and failure to thrive. The 1st generation diphenhydramine (Benadryl) is also linked with weight gain when used on a long-term basis. Other 1st generation antihistamines include brompheniramine, chlorpheniramine, and hydroxyzine.

Alternatives

Nasal corticosteroids such as triamcinolone nasal spray (Nasacort Allergy 24HR Nasal Spray) or fluticasone nasal spray (Flonase Allergy Relief) won't cause weight gain and may be better options for hay fever or other allergy symptoms, especially if weight gain is a concern.

Although nasal corticosteroid sprays are often preferred for allergies (allergic rhinitis), the antihistamine nasal sprays such as azelastine (Astepro, Astelin) and olopatadine (Patanase) are also available.

3. Antipsychotics and Mood Disorder Treatments

These drugs are used to treat mental health conditions such as schizophrenia, bipolar disorder, or as an add-on treatment with an antidepressant for difficult-to-treat depression. Although all of the drugs in the antipsychotic class have been shown to produce some metabolic and weight changes, each drug has its own specific risk profile.

Many antipsychotics are well-known to cause weight gain. Research by Huang and colleagues has shown an enzyme called AMP-kinase is elevated in the brain of patients who use antipsychotics. AMP-kinase can block the brain histamine-1 receptor, which can increase appetite and weight gain.

However, for mental health disorders, drug treatment may be absolutely necessary and alternatives may not be appropriate. The risk of stopping the drug may be greater than the risk associated with weight gain. If you are taking any prescription, do not stop treatment without first speaking to your doctor.

Patients taking antipsychotic drugs should have their weight, waist circumference, lipids, blood pressure, and blood glucose (sugar) monitored at the recommended intervals.

Weight gain

Antipsychotics are frequently linked with weight gain. Examples linked with weight gain include the atypical antipsychotics such as olanzapine (Zyprexa), risperidone (Risperdal), aripiprazole (Abilify) and quetiapine (Seroquel).

Brexpiprazole (Rexulti), approved in 2015, is also associated with weight changes. In long-term studies, 30% of patients demonstrated a ≥7% increase in body weight, and 4% demonstrated a ≥7% decrease in body weight.

Clozapine (Clozaril), an older, atypical antipsychotic has also been associated with significant weight gain. Patients may gain from 7% to 10% of their body weight. These drugs can block histamine and serotonin, which may contribute to the weight gain effect.

The original "typical" antipsychotics such as haloperidol (Haldol), chlorpromazine, fluphenazine, and thioridazine can cause weight gain, but these drugs are used less frequently due to abnormal movement disorders that can occur. Haloperidol and fluphenazine have the lowest risk of the 1st generation agents.

Many of the antipsychotics may impair glucose (sugar) control and lead to insulin resistance, impaired glucose tolerance and type 2 diabetes. However, these drugs may be necessary for treatment of bipolar disorder, severe depression, or schizophrenia and for the safety of the patient. Patients or caregivers must speak with their physician before stopping treatment.

Weight neutral or less risk of weight gain

• While no antipsychotic is completely void of metabolic side effects, ziprasidone (Geodon), lurasidone (Latuda), and pimavanserin (Nuplazid) are more weight neutral antipsychotics.
• Nuplazid is indicated specifically for psychosis (hallucinations and delusions) that is related to Parkinson's disease.

4. Beta blockers

Weight gain, especially if it's rapid, can be a medical concern with any heart drug. If your weight gain is due to fluid retention (edema), it may be dangerous for your heart or lungs and you should contact your doctor right away. You may need a special medicine called a diuretic to help with your fluid (water) retention.

Beta blockers are an older class of heart drug used to treat high blood pressure, chest pain (angina), and protect or prevent the heart from a heart attack.

• Beta blockers have long been known to lead to weight gain. Common examples of this class are propranolol, metoprolol (Lopressor) and atenolol (Tenormin).
  • Many of the older beta blocker drugs can lead to fatigue, which may be responsible for some of the weight gain.
  • Patients may be tired, have lack of energy, and slow down, which may affect the number of calories burned each day.

Other blood pressure medications like the angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers (ARBs), or calcium channel blockers are less likely to cause weight gain, and may be an option for you.

5. Birth Control

In general, the birth control pill is not linked with weight gain, especially the newer pills with lower doses of estrogen and progestin. However, higher doses of estrogen or progestin-only birth control can cause weight gain.

The birth control shot known as medroxyprogesterone (Depo-Provera) that is given every 3 months can cause significant weight gain in some women.

6. Corticosteroids

Corticosteroid ("steroid") medications are used for many different conditions (for example: asthma, allergies, arthritis, acute injury) to help lower inflammation, pain and swelling. They are often used short-term and the dose is slowly decreased, which can help lessen side effects. Long-term use of corticosteroid drugs can be linked with many more serious side effects and is avoided when possible.

Corticosteroid can affect the metabolic rate and lead to increased appetite and overeating. This class of drug can also lead to extra deposits of fat in your midsection (stomach area).

Oral corticosteroids (glucocorticoids) may carry a risk of weight gain with high dose and long-term use. Oral corticosteroids might be used for severe asthma or painful inflammatory conditions such as rheumatoid arthritis or inflammatory bowel disease.

Examples of corticosteroids include prednisone, methylprednisolone (Medrol Dosepak), prednisolone (Orapred ODT) and triamcinolone (Kenalog).

Weight neutral

Local injectable corticosteroids, such as injections in the knee joint or spinal column for inflammation, and inhaled corticosteroids used for asthma, are not associated with weight gain.

For pain that requires longer-term treatment, such as mild to moderate arthritis pain, acetaminophen (Tylenol) or an NSAID like ibuprofen (Advil, Motrin) or naproxen (Aleve) may be alternatives.

7. Diabetes medications

Diabetes drugs are used to help control blood sugar by helping to release more insulin from the pancreas or making the insulin more responsive when it is released. Insulin itself can also be injected.

Weight gain

Some drugs used in the treatment of type 2 diabetes can lead to weight gain and fluid retention.

Certain oral medications for type 2 diabetes, such as glyburide (DiaBeta), glimepiride (Amaryl) and glipizide (Glucotrol), members of the sulfonylurea class, can lead to weight gain. These agents lower blood glucose by stimulating insulin release, which can result in an elevated appetite.

• Insulin injection is required in type 1 diabetes and may be needed in some people with type 2 diabetes. Injectable insulin itself can also lead to significant weight gain, as insulin use allows glucose to enter your cells instead of staying in your blood. Too many calories in the form of glucose will lead to weight gain. Excess glucose ends up as fat if it's not burned off with exercise.
• Examples of insulin are insulin isophane (Humulin N), insulin lispro (Humalog), insulin aspart (Novolog), insulin glargine (Lantus) or insulin glulisine (Apidra).

Type 2 diabetes drugs in the class known as thiazolidinediones can lead to weight gain and an increase in fat. Example drugs include pioglitazone (Actos) and rosiglitazone (Avandia). These drugs have a Boxed Warning about excessive, rapid weight gain; dyspnea (shortness of breath); and edema that may indicate the onset of heart failure.

Weight neutral

There are some type 2 diabetes treatments that are more likely to be weight neutral or associated with weight loss.

• Metformin (Glumetza), an oral medicine, is often the first drug used in the treatment of type 2 diabetes. Metformin tends to be weight neutral, meaning there's usually no significant gain or loss of weight due to the drug.
• Dipeptidyl Peptidase 4 (DPP-4) Inhibitors: for example, alogliptin (Nesina), linagliptin (Tradjenta), sitagliptin (Januvia), and saxagliptin (Onglyza) also have a more neutral effect on weight.
• The alpha-glucosidase inhibitors, such as acarbose and miglitol (Glyset) also tend to be more weight neutral.

Weight loss

The glucagon-like peptide-1 receptor agonists (GLP-1 agonists), also called the incretin mimetics, are glucose-lowering drugs that have been shown to have a positive effect on weight and fat distribution.

• • Examples include: albiglutide (Tanzeum), dulaglutide (Trulicity), exenatide (Bydureon, Byetta), liraglutide (Victoza), lixisenatide (Adlyxin), and semaglutide (Ozempic, Rybelsus).
  • In fact, one brand of liraglutide, known as Saxenda, is a GLP-1 agonist used specifically for weight loss, but it's NOT approved for use in diabetes. Only one GLP-1 agonist should be used at a time.
  • Other more recent GLP-1-like agents (incretin mimetics) approved for type 2 diabetes or weight loss include Mounjaro, Ozempic, Rybelsus, Wegovy, and Zepbound. These agents have been associated with significant weight loss when used in addition to diet and exercise.

The selective sodium-glucose co-transporter 2 inhibitors (SGLT-2 inhibitors), also glucose-lowering agents, can lead to moderate effects on weight loss, examples include:

• canagliflozin (Invokana), empagliflozin (Jardiance), ertugliflozin (Steglatro) and dapagliflozin (Farxiga).
• Another advantage is that some of these medicines are approved to lower the risk of death from heart attack, stroke, or heart failure in adults with type 2 diabetes who also have heart disease.

8. Anticonvulsants, mood stabilizers and migraine medicines

Some anticonvulsant drugs can be associated with significant weight gain; up to 30 to 40 lbs (15 to 20 kg) in some cases over the long-term. Obesity itself is also linked with migraine. As obesity increases, so does the risk and severity of migraine headaches.

Weight gain

• Divalproex (Depakote) is used to treat epilepsy (seizures), bipolar disorder and for migraine prevention. Other agents that can affect weight include carbamazepine (Carbatrol, Tegretol, Epitol), pregabalin (Lyrica) and gabapentin (Neurontin, Horizant).
• Lithium (Lithobid) is also commonly used for mood disorders and is associated with a significant weight gain. Up to 65% of patients may gain over 20 lbs (10 kg) after many years of use.

Weight loss or weight neutral

Common drugs used for migraine prevention (propranol) or seizures (Depakote) can cause weight gain. Since these medicines are typically used long-term, the risk is greater. There are alternatives you might want to discuss with your doctor.

• Topiramate (Qudexy XR Sprinkle, Topamax), used for seizures or migraine headaches, might actually suppress appetite and cause weight loss in some people.
• Other anti-seizure medications used for migraine prevention may lead to weight loss and include zonisamide and protriptyline.
• A newer class of migraine medicines called CGRP inhibitors, used to treat or prevent migraine, is unlikely to cause significant weight gain. CGRP inhibitors used to prevent migraine headache include Aimovig, Emgality, Ajovy and Nurtec ODT.

Table of Common Medicines That Cause Weight Gain

Learn More:

• Medications for Weight Loss

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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