Weight Gain as a Side Effect of Medications
Yes, weight gain is a significant side effect of many commonly prescribed medications, with some drugs causing patients to gain as much as 10 kg in a relatively short period of 36 months. 1
Medications Associated with Weight Gain
Antidiabetic Medications
- Insulin, thiazolidinediones, sulfonylureas, and meglitinides are associated with significant weight gain, while metformin, GLP-1 agonists, SGLT-2 inhibitors, and pramlintide promote weight loss or are weight-neutral 1
- Patients can gain up to 10 kg within 36 months of initiating treatment with weight-promoting antidiabetic agents 1
Antihypertensive Medications
- Beta-blockers (particularly non-selective ones) can promote weight gain by decreasing metabolic rate and affecting energy metabolism 1, 2
- Alpha-blockers like doxazosin are associated with significant weight gain, likely due to extracellular fluid volume expansion 1
- Weight-neutral alternatives include angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and calcium channel blockers 1
Psychiatric Medications
Antipsychotics: Olanzapine, clozapine, quetiapine, and risperidone consistently cause significant weight gain 1
Antidepressants: Weight effects vary significantly within classes 1, 6
- Paroxetine has the highest risk of weight gain among SSRIs 1, 6, 7
- Fluoxetine and sertraline typically cause initial weight loss followed by weight neutrality with long-term use 1, 6
- Bupropion is the only antidepressant consistently shown to promote weight loss 1, 6, 7
- Tricyclic antidepressants (especially amitriptyline), lithium, mirtazapine, and monoamine oxidase inhibitors are associated with significant weight gain 1
Anticonvulsants/Anti-epileptic Drugs
- Gabapentin, pregabalin, valproic acid, and carbamazepine are consistently associated with weight gain 1, 8
- Topiramate and zonisamide promote weight loss 1, 8
- Lamotrigine, levetiracetam, and phenytoin are generally weight-neutral 1, 8
Other Medications
- Antihistamines: First-generation (sedating) antihistamines that cross the blood-brain barrier are more likely to cause weight gain than non-sedating alternatives 1
- Hormonal agents: Oral glucocorticoids are frequently associated with weight gain 1, 9
- Contraceptives: Medroxyprogesterone acetate shows evidence of weight gain, while combination oral contraceptives have variable effects 1
Clinical Implications and Management
Weight gain from medications can lead to:
Management strategies:
- When possible, select weight-neutral or weight-loss promoting alternatives within the same drug class 1
- Use the lowest effective dose for the shortest duration necessary 1
- Consider adding metformin to regimens that include weight-promoting antidiabetic agents 8
- Regular monitoring of weight in patients taking medications known to cause weight gain 6
- For patients with significant weight concerns, consider switching to more weight-neutral alternatives if clinically appropriate 7
Common Pitfalls and Caveats
- Weight gain is often underrecognized as a medication side effect, leading to poor adherence when patients discontinue medications without informing their healthcare providers 9
- In clinical trials, weight change is frequently recorded under safety outcomes rather than as a primary outcome measure, potentially underestimating its significance 10
- The weight impact of medications can be difficult to predict in individual patients due to variability in response 1
- Patients taking medications associated with weight gain may have more difficulty losing weight in structured weight management programs 11
- When prescribing anti-obesity medications, be aware that all are classified as pregnancy category X 1