Almost any medication can cause side effects, but some can create a surprising challenge: weight gain. This isn’t just a cosmetic concern — even small increases in weight can affect your overall health and, in some cases, interfere with recovery from the very condition you’re trying to treat.
Weight gain may not seem critical, especially when treating serious conditions, but even modest gains (5 to 20 pounds) can harm overall health, one study shows. Obesity increases the risk of diseases like heart disease, stroke, and death, according to the Centers for Disease Control and Prevention
8 medications that could cause weight gain
1. Diabetes drugs
Maintaining a healthy weight is an important part of any treatment for type 2 diabetes. But here’s the rub: Some of the drugs prescribed to help manage the condition often result in weight gain.
Diabetes drugs that may cause weight gain include:
- Injectable insulin: The hormone works by helping the body’s cells absorb glucose. Insulin causes a spike in weight, however, when the cells absorb too much glucose and the body converts it into fat. Not everyone with type 2 diabetes is on insulin. But insulin isn’t the only type 2 treatment that carries this side effect.
- Sulfonylureas (such as glyburide, glipizide, and glimepiride) reduce blood sugar levels by 20 percent, but they can also can also cause a weight gain of 4 to 5 pounds on average, according to a study published in Archives of Medical Science. That’s because they stimulate beta cells in the pancreas to release insulin.
What to do: These medications have been used for many years and are often commonplace in diabetes management, but there are newer medications that promote weight loss and should be considered,” Batsis says. A class of type 2 diabetes drugs known as glucagon-like peptide 1 (GLP-1) agonists can cause patients to lose a significant amount of weight 15 to 20 percent of their body weight. Some of the more common names in this class include semaglutide (Ozempic) and tirzepatide (Mounjaro).
2. Antidepressants
If you’ve been on an antidepressant for a while and you’ve put on weight, it could be a sign of improved mood if weight loss was a symptom of your depression.
Significant weight gain, on the other hand, is likely a side effect of the medication itself, especially if you’re taking an SSRI (short for selective serotonin uptake inhibitor), the most commonly prescribed class of antidepressants. These medications increase "the amount of serotonin in your brain, which is a key neurotransmitter involved in depression,” Batsis says. “Serotonin, though, is also implicated in the biological and neurotransmitter processes that regulate weight and appetite. There are many serotonin receptors, but at a high level, they interfere with this process.”
Antidepressants that may cause weight include:
- Paroxetine (Paxil)
- Sertraline (Zoloft)
- Citalopram (Celexa)
What to do: With many of the newer second-generation antidepressants, there is often no weight gain; some, such as bupropion (Wellbutrin), may even result in weight loss, Batsis says, echoing the results of research published in 2018 in the journal Diabetes, Metabolic Syndrome and Obesity.
“Bupropion is less likely to cause weight gain and when coupled with naltrexone (Vivitrol) is a potential treatment for obesity,” he says. “Yet in older adults, bupropion, while safe, needs to be counterbalanced with other medical issues as it may have more central nervous system side effects.”
Beta-blockers work by slowing the heart rate, the heart’s workload and its output of blood, all of which lowers blood pressure. That’s why they’re often prescribed as a treatment for hypertension, angina and irregular heartbeat. If you’re on a beta-blocker, no one has to tell you the side effects include fatigue, insomnia and a slow heartbeat. All of those can add up to a less physically active lifestyle, which — no surprise — may result in extra weight.
“Weight gain often occurs in the first few months after initiating beta-blockers like atenolol or metoprolol,” Batsis says. That’s “thought to be due to changes in metabolism, insulin sensitivity and impact on skeletal muscle metabolism.”
Medications That May Cause Water Retention
Certain medications may cause swelling, some lead to water or sodium retention, while others cause fluid to move from inside cells or blood vessels to surrounding tissues. Below is a list of medications known for causing this side effect and considerations for managing it:
- Calcium channel blockers: Amlodipine (Norvasc), nifedipine (Adalat, Procardia)
- Pioglitazone (Actos), used for diabetes management
- NSAIDs: Ibuprofen (Advil, Midol, Motrin), naproxen (Aleve, Anaprox, Naprosyn) diclofenac (Voltaren), celecoxib (Celebrex)
- Minoxidil tablets (Loniten, Minodyl)
- Steroids Hydrocortisone tablets or IV (Cortef, Hydrocortone)
Managing Water Retention:
- Dose adjustments: Lowering the dose may reduce swelling for some medications.
- Add-on medications: Other drugs can sometimes offset water retention.
- Medication substitution: In cases where adjustments aren’t effective, switching to a different medication might be necessary.
4. Oral corticosteroids
Oral corticosteroids are prescribed for everything from severe allergies and rashes to rheumatoid arthritis, but they come with side effects — among them, weight gain. The culprit? Fluid retention.
“Electrolyte imbalances lead to water retention,” Umashanker explains. “Oral steroids also reduce the body’s sensitivity to insulin, leading to insulin resistance.” That, in turn, ramps up production of the hunger hormone ghrelin, which stimulates appetite.
Oral corticosteroids that may cause weight gain include:
- Prednisone (Deltasone, Predone, Sterapred)
- Cortisone (Cortone)
- Hydrocortisone (Cortef, Hydrocortone)
- Methylprednisolone (Medrol)
What to do: To avoid weight gain, Umashanker recommends a diet rich in low-glycemic foods such as fruits and vegetables, beans, minimally processed grains, low-fat dairy and nuts, all of which are “slowly digested and absorbed, causing a slower and smaller rise in blood sugar levels.”
4. Oral corticosteroids
Oral corticosteroids are prescribed for everything from severe allergies and rashes to rheumatoid arthritis, but they come with side effects — among them, weight gain. The culprit? Fluid retention.
“Electrolyte imbalances lead to water retention,” Umashanker explains. “Oral steroids also reduce the body’s sensitivity to insulin, leading to insulin resistance.” That, in turn, ramps up production of the hunger hormone ghrelin, which stimulates appetite.
Oral corticosteroids that may cause weight gain include:
- Prednisone (Deltasone, Predone, Sterapred)
- Cortisone (Cortone)
- Hydrocortisone (Cortef, Hydrocortone)
- Methylprednisolone (Medrol)
What to do: To avoid weight gain, Umashanker recommends a diet rich in low-glycemic foods such as fruits and vegetables, beans, minimally processed grains, low-fat dairy and nuts, all of which are “slowly digested and absorbed, causing a slower and smaller rise in blood sugar levels.”
Migraine medications that may cause weight gain include:
Propranolol (Inderal)
Divalproex sodium (Depakote).
According to the American Migraine Foundation, people at a healthy weight who experience migraines have about a 3 percent chance of developing chronic headaches. For people who are overweight and for people with obesity, the chance of chronic migraine is three to five times greater.
What to do: If you’re on a migraine-preventive medication that’s causing weight gain, talk to your doctor about switching to one that has the potential to suppress appetite, such as topiramate (Topamax), zonisamide (Zonegran) or protriptyline (Vivactil).
6. Antihistamines
It’s easy to assume that over-the-counter meds don’t carry serious side effects because they’re so readily available. But just because something is available without a prescription doesn’t mean it’s risk-free. Research suggests that taking an antihistamine on a regular basis — to treat allergies, for instance — can result in weight gain.
Antihistamines that may cause weight gain include:
- Cyproheptadine (Periactin)
- Cetirizine (Zyrtec)
- Fexofenadine (Allegra)
- Desloratadine (Clarinex)
“The major study which demonstrates the relationship between antihistamines and weight gain comes from the journal Obesity,” Umashanker says. “It revealed that men who used antihistamines had an average weight of 214 pounds versus 192 for those not on antihistamines, and women had an average weight of 176 pounds on antihistamines versus 166 pounds for those not on antihistamine.”
Why? Histamine, a chemical in the body known to be a key player in allergic responses, decreases hunger by affecting the appetite control center in the brain, so it makes sense that an antihistamine would have the opposite effect, interfering with the “I’m full” signal coming from the rest of the body, according to the Obesity Medicine Association.
6. Antihistamines
It’s easy to assume that over-the-counter meds don’t carry serious side effects because they’re so readily available. But just because something is available without a prescription doesn’t mean it’s risk-free. Research suggests that taking an antihistamine on a regular basis — to treat allergies, for instance — can result in weight gain.
Antihistamines that may cause weight gain include:
- Cyproheptadine (Periactin)
- Cetirizine (Zyrtec)
- Fexofenadine (Allegra)
- Desloratadine (Clarinex)
“The major study which demonstrates the relationship between antihistamines and weight gain comes from the journal Obesity,” Umashanker says. “It revealed that men who used antihistamines had an average weight of 214 pounds versus 192 for those not on antihistamines, and women had an average weight of 176 pounds on antihistamines versus 166 pounds for those not on antihistamine.”
Why? Histamine, a chemical in the body known to be a key player in allergic responses, decreases hunger by affecting the appetite control center in the brain, so it makes sense that an antihistamine would have the opposite effect, interfering with the “I’m full” signal coming from the rest of the body, according to the Obesity Medicine Association.
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