Alternatives to Medications That Cause Weight Gain

Summary of the Endocrine Society's Guideline on the Pharmacological Management of Obesity

This article is the fourth in a 4-part series on the Endocrine Society’s clinical practice guideline on the pharmacological management of obesity. This section presents an overview of medications that can cause weight gain.

Medications used for the treatment of comorbid conditions in adults with obesity may contribute to, or exacerbate, weight gain in certain patients. These medications include certain diabetes medications, antidepressants, antipsychotics, antiepileptics, injectable contraceptives, antiretrovirals, chronic corticosteroid therapy, and antihistamines.

The guideline provides evidence to guide selection of agents with the least potential for weight gain or that promote weight loss when treating these conditions. The task force recommends using a shared decision-making process that includes information on expected weight gain when choosing pharmacotherapy.

Diabetes Medications
For patients with obesity and type 2 diabetes, use of anti-diabetes medications that also promote weight loss—such as metformin, GLP-1 analogs (eg, exenatide, albiglutide, dulaglutide and liraglutide) or SGLT-2 inhibitors (dapagliflozin, empagliflozin and canagliflozin) are recommended. For patients with diabetes who are taking insulin, the task force suggested adding pramlintide or GLP-1 agonists to the therapeutic regimen to mitigate the likelihood for weight gain with insulin. Basal insulin should be the first-line therapy in adults with obesity requiring insulin therapy.  

For patients with hypertension (in addition to obesity and diabetes), the task force recommends angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers rather than β-adrenergic blockers.

Antidepressants have considerable variability in terms of their weight gain potential. For example, paroxetine, amitryiptyline, mirtazapine, and nortriptyline are linked to weight gain with long-term use. Many other agents are weight neutral. Bupropion is the only antidepressant that consistently has been linked to weight loss, and is therefore recommended for patients with overweight or obesity.

While atypical antipsychotics are better tolerated than older antipsychotics, many of the newer agents are associated with weight gain. Clozapine and olanzapine, for example, are linked with a greater likelihood for weight gain, while ziprasidone appears to be linked to the lowest risk for weight gain.

The weight gain potential of antiepileptics varies considerably by agent (Table). The task force recommends considering the weight gain potential of these agents when choosing an antiepileptic for any patient.

Given that injectable contraceptives are associated with weight gain, oral contraceptives are preferred for women with a body mass index (BMI) >27 kg/m2 with comorbidities or BMI >30 kg/m2 seeking contraception. Findings on the weight gain potential of contraceptives are conflicting, and different formulations are difficult to compare because of variability in estrogen dosing and use of different progestins. Women should be informed of the risks and benefits of all contraceptives. The task force noted that some studies suggest that women with a BMI >27 kg/m2 are at increased risk for contraceptive failure; however, the data is conflicting and should be discussed with patients on an individual basis.

Antiretroviral Therapy
Antiretroviral therapies used in the treatment of HIV are linked to unavoidable weight gain, increased visceral adipose tissue, and lipodystrophy. The task force recommends monitoring weight and weight circumference in patients on antiretroviral therapy.

Treatments for Chronic Inflammatory Diseases
In the treatment of chronic inflammatory diseases in adults who have overweight or obesity, nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs are preferred over corticosteroids, which are associated with weight gain.

Studies suggest that antihistamines with greater potency pose a greater risk for weight gain. Thus, the Task force recommends using antihistamines with less sedation (ie, less central nervous system activity) to limit weight gain. 

Read other sections of the clinical practice guideline summary:


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Overview of the Endocrine Society's Guideline on Obesity Medications
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