Applied Evidence

Drug-induced weight gain: Rethinking our choices

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Weight gain secondary to medications is a potentially modifiable risk. Here’s how to optimize drug choices for patients with several common conditions.




› Choose weight-loss-promoting medications, such as metformin, sodium-glucose co-transporter 2 inhibitors, and glucagon-like peptide-1 agonists, and weight-neutral medications, such as DPP-4 inhibitors, as first- and second-line agents for patients with type 2 diabetes who are overweight or obese. A
› Prescribe angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or calcium channel blockers as first- and second-line antihypertensive therapy for patients who are overweight or obese. A
› Select antidepressants that promote weight loss, such as bupropion, or weight-neutral agents, such as fluoxetine and sertraline, for patients who are overweight or obese and require treatment for depression. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Medications can have an unpredictable and variable effect on weight. Some drugs trigger weight gain in one patient while inducing weight loss in another. Others may lead to weight loss initially but cause weight gain when taken long term.1 Often, a drug’s effect on a patient’s weight depends on his or her medical history and lifestyle, including factors like insulin resistance, diet, and exercise level.

To make matters worse, clinical studies of drug-related effects on weight can be misleading. Because researchers often report a mean weight change—an average of those who had little or no change in weight when taking the drug and individuals who may have gained a significant amount of weight—a drug’s potential to cause weight gain may be underestimated. Few studies include an analysis of the range—eg, how many participants gained or lost various percentages of body weight. What’s more, pharmacology studies typically follow participants for a few months to a few years, whereas weight changes can be cumulative when a medication is taken for many years.

The nation’s continually growing obesity epidemic makes it crucial for physicians to consider the weight effects of medications being prescribed and to balance the benefits of treatment with the potential for weight gain. Until recently, the medical literature offered little guidance.

In 2015, the Endocrine Society published clinical practice guidelines for pharmacologic management of obesity, including data on medications that cause weight gain and suggesting alternatives that are weight-neutral or promote weight loss.2

In the pages that follow, we present case studies, tables, and a review of the latest evidence to highlight optimal drug treatment for patients who are overweight or obese, and are also being treated for diabetes, hypertension, and depression. You’ll find a brief discussion of weight management strategies related to other drugs and conditions in the sidebar.2-5

Drug-induced weight gain: Rethinking our choices image

CASE 1 › 40-year-old man with diabetes and hyperlipidemia

Brian P, who has come in for an annual checkup, has a body mass index (BMI) of 30 kg/m2. He also has hyperlipidemia and type 2 diabetes, for which he has been taking metformin for several years. A year ago, his hemoglobin A1c (HbA1c) was 7.3%, so his physician added glyburide to his regimen.

In the year since, Mr. P has gained 12 lbs (5.4 kg) but achieved only a minimal reduction in HbA1c (to 6.8%). He expresses concern about the cardiovascular effects of the extra weight and says that diet and exercise have not helped him control his weight.

CASE 2 › Older woman with hypertension and hypothyroidism

Addie K, age 64, is obese (BMI, 37 kg/m2) and has hypertension and hypothyroidism, for which she takes metoprolol and levothyroxine. Ms. K says that she is careful about what she eats and exercises several times a week, but still has seen her weight increase steadily for the past several years.

The nation's obesity epidemic makes it crucial for physicians to consider the weight effects of medications being prescribed and to balance the benefits of treatment with the potential for weight gain.

CASE 3 › Young man with depression

Charlie D, a 21-year-old college student, is a new patient. He has depression and is obese (BMI, 34 kg/m2). The patient says he was diagnosed with depression by his former primary care physician, who prescribed paroxetine a year ago. He requests a refill of the paroxetine, which he reports has successfully boosted his mood. When asked about his weight, he admits that he has gained 8 lbs (3.6 kg) since he began taking the drug.

If these were your patients, what weight management steps would you take? Before we provide some recommendations, let’s review the evidence.


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