Avoid Weight-Promoting Medications in Patients With Obesity

While diet, exercise, and behavior modification are key components of weight management, several physiological mechanisms act to preserve excess body weight, necessitating consideration of and conversations with the patient.

With Leon I. Igel, MD, and Scott Isaacs, MD

Weight gain secondary to medications is a modifiable risk factor for obesity. For patients with obesity and comorbid diabetes, hypertension, or depression, selecting the right medication can prevent undesirable weight gain and even promote weight loss.

Since many patients fail to sustain meaningful weight loss, in reporting on the Practical Use of Pharmacotherapy for Obesity,1 Leon I. Igel, MD, and colleagues, prompt clinicians to consider a medication’s effect on weight as part of the evaluation of potential side effects and interactions when selecting a medication. 

“Physicians know that some medications can increase weight, but they don’t always know what alternatives are out there,” Dr. Igel, an assistant professor of clinical medicine in the Division of Endocrinology, Diabetes, and Metabolism at Weill Cornell Medicine, told EndocrineWeb.

“It’s important for physicians to familiarize themselves with alternatives that may limit weight gain or may even assist with weight loss and to feel comfortable discussing these options with their patients,” he said.

Choose medications that will not promote weight gain in people with obesity.

Consider Weight Effects of Diabetes Medications 

This is especially true when managing diabetes where weight gain is strongly associated with insulin, and glucose-lowering medications that act directly on insulin, including thiazolidinediones (TZDs), sulfonylureas, and meglitinides.1However, antidiabetic medications that work through other mechanisms are proven to be weight-neutral or to promote weight loss.

“Now that we realize that insulin may not be the best option for an obese patient, especially one who already has cardiovascular disease or is at increased risk, it makes sense to choose a medication that balances insulin’s effects on weight gain,” Dr. Igel told EndocrineWeb. “New medications are being approved that have weight loss effects as well as cardiovascular benefits, and our research is intended to help clinicians make well-informed choices.”

Select Weight Neutral Antidiabetes Medications

  • Metformin works through multiple mechanisms including changes in hypothalamic physiology to prompt a decrease in food intake.
  • The glucagon-like-peptide 1 (GLP-1) agonists enhance glucose-dependent insulin secretion, slow gastric emptying, and reduce postprandial glucagon, all leading to a decrease in appetite and an enhanced feeling of satiety.
  • Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce glucose reabsorption by the kidneys, leading to increased urinary glucose excretion.
  • Dipeptidyl peptidase IV (DPP-4) inhibitors and alpha-glucosidase inhibitors (AGIs) appear to be weight neutral or lead to minimal changes in weight.
  • Pramlintide, the amylin analog used in combination with insulin, increases satiety and decreases food intake.

For patients with obesity and type 2 diabetes requiring insulin, the Endocrine Society Clinical Practice Guidelines recommend prescribing at least one weight loss-promoting medication, such as metformin, a GLP-2 agonist, or pramlintide, to mitigate the weight gain associated with insulin use.2

“Various GLP-1 and SGLT2 inhibitors may have different effects on weight or have a cardiovascular benefit, and these should be discussed with patients. There are only limited data available, however, so a drug may have a benefit, but it hasn’t been shown in a clinical study," Scott D. Isaacs, MD, an endocrinologist, and obesity specialist in Atlanta, GA, told EndocrineWeb. "Cardiovascular safety studies are still ongoing and more data are expected in the next 1-3 years. GLP-1s are better for weight loss than SGLT2s.”

I have prescribed SGLT2s occasionally for people with diabetes to support weight loss, and it should be noted that Johnson & Johnson is investigating an SGLT2 combination product that will have an indication for weight loss, according to Dr. Iger. 

“As an obesity specialist, I frequently prescribe GLP-1s off-label for weight loss but never prescribe SGLT2 for weight loss, only diabetes. Liraglutide seems to be best for weight loss but there are no good head-to-head studies comparing the agents for weight loss since only liraglutide is approved for that indication,” said Dr. Isaacs.

Select Antihypertensive Medications for Weight-Neutrality

  • Angiotensin is overexpressed in obesity and contributes to obesity-related hypertension, making angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) desirable options for the treatment of patients with obesity.
  • Like ACE inhibitors and ARBs, calcium channel blockers (CCBs) are considered weight-neutral.
  • Beta-adrenergic blockers (β-blockers), on the other hand, can promote weight gain and prevent weight loss through several mechanisms, including potential adverse metabolic effects on lipids and/or insulin sensitivity, as well as negative effects on metabolism.

However, selective β-blockers with a vasodilating component, such as carvedilol and nebivolol, are recommended in patients with coronary artery disease, heart failure, or arrhythmias who require a β-blocker.2 These agents appear to have less potential for weight gain and minimal effects on lipid and glucose metabolism.

Other antihypertensive agents that should be avoided in patients with obesity include the alpha-adrenergic blocker doxazosin, because of its effect on extracellular fluid volume expansion leading to weight gain, and the thiazide diuretics, because of their dose-related effects on hyperlipidemia and insulin resistance.3

Let Patient’s Condition Guides Antidepressant Therapy  

Weight gain commonly occurs as an adverse side effect of numerous antidepressants,1,4but there is a range of weight gain potential within classes.

  • Among the selective serotonin reuptake inhibitors (SSRIs), fluoxetine and sertraline may cause weight loss at first and weight-neutrality with long-term use, although paroxetine is associated with the greatest risk for weight gain.
  • The tricyclic antidepressant, amitriptyline, and the tetracyclic antidepressant, mirtazapine, are associated with the greatest risk for weight gain.
  • Bupropion, a norepinephrine and dopamine reuptake inhibitor is the only antidepressant that has consistently been shown to promote weight loss.

Unfortunately, not all antidepressants are interchangeable and the choice of an agent must be guided by the individual patient’s circumstances, noted Dr. Igel.  

Final Thoughts

“A prudent physician needs to assess the weight-related side effects when selecting a drug for hypertension, contraception, diabetes, seizures or psychiatric conditions. This article does a good job summarizing the recommendations from the Endocrine Society Guidelines published in 2015,” said Dr. Isaacs. 

“Obesity management requires a multidisciplinary approach, and weight gain secondary to medications is an important modifiable risk factor," said Dr. Igel. "Our study aims to provide guidance in selecting an optimal treatment regimen for patients with obesity that minimizes the potential for further weight gain and may contribute to weight loss. When possible, practitioners should utilize weight-neutral or weight-reducing medications. If no alternative is available, weight gain can be prevented or lessened by selecting the lowest dose of a medication required to produce clinical efficacy for the shortest duration necessary.” 

 

Continue Reading:
Diabetes Drug Liraglutide Shows Promising Weight Loss Benefit
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