The discovery that Ozempic (semaglutide) supports weight loss is not new, but the unexpected spotlight on weight loss as a side effect of a diabetes medication serves as a good reminder to healthcare providers (or a wake-up call, for some) that all medications’ potential effects on weight should be taken into account, because the opposite result — drug-induced weight gain — is more common than most practitioners realize.

A typical case

A 33-year-old woman, Jill, recently presented to my obesity medicine practice because she had suddenly started to gain weight — 32 pounds over the previous six months. Through my evaluation, I learned that she had received two Depo-Provera injections during that time. She had previously used oral contraceptive pills, but she often forgot to take her pills and wanted a lower-maintenance form of birth control. Although progestin injections work well for many women, weight gain is a known and fairly common side effect, and the timing of Jill’s weight gain suggested a causal link. As part of her weight-management plan, we discussed birth control alternatives, and she ultimately chose to switch to a nonhormonal IUD.

The OB-GYN who prescribed her Depo-Provera had not mentioned the possibility of weight gain. While it’s understandable that many practitioners don’t want to create unnecessary worry about a side effect that might never materialize, it can be extremely difficult to lose weight once it has been gained, particularly for those who already have overweight or obesity. Since many patients who don’t track their weight can gain significant amounts without realizing it, simply advising patients to monitor their weight and notify their provider if they notice an increase can prevent tremendous frustration.

Jill was on only one weight-gain-promoting medication, but I often identify two, three, or even four such culprits when taking a new patient’s history. In addition to injectable or implantable birth control, some of the most common weight-gain-promoting drugs include diabetes medications, blood pressure medications, and antidepressants. In many cases the effect is modest, but with long-term medication use for chronic conditions, even a small effect can lead to a significant increase in weight over time.

Prevention starts with awareness

What can healthcare practitioners do to help their patients avoid drug-induced weight gain? Essentially, four things:

1. Be aware. First, practitioners need to recognize how common the problem is and educate themselves about the weight profiles of various classes of drugs and different agents within classes. (The Endocrine Society’s practice guidelines for the pharmacological management of obesity include information on drugs that cause weight gain and recommended alternatives; see the original article in the Journal of Clinical Endocrinology and Metabolism, or a summary listing in Table 2 of our more recent best practices article.) As with most contributors to the multifactorial disease of obesity, the interactions are complex, and a medication’s impact on weight may vary based on a variety of physiological, genetic, and lifestyle factors. But despite some unpredictability, many medications do have a well-documented track record of promoting weight gain, and providers should be alert to this potential side effect.
2. Choose alternatives when possible. When prescribing any medication, providers should consider the drug’s weight profile in assessing the benefits and risks, and seek to avoid weight-promoting drugs when possible. Weight-neutral or weight-loss-promoting medications are available for many common conditions that are frequently associated with obesity, including type 2 diabetes, hypertension, and depression. These alternatives should be prioritized when appropriate as first- and second-line treatments — especially for patients with overweight, obesity, or metabolic risk factors. For example, for patients with type 2 diabetes, weight-loss-promoting medications such as metformin and glucagon-like peptide-1 (GLP-1) receptor agonists (semaglutide and liraglutide, for instance), or weight-neutral options such as DPP-4 inhibitors, are preferred over insulin and insulin secretagogues that promote weight gain. For patients with hypertension, weight-neutral angiotensin-converting enzyme inhibitors or angiotensin receptor blockers should be chosen over weight-gain-promoting alpha- or beta-adrenergic blockers if possible. Many antidepressants present a risk of weight gain, for example, but only one, bupropion, has been consistently shown to promote weight loss, though it’s not appropriate for all patients. When recommending changes to existing prescriptions, providers should either consult with the original prescribing physician or ensure that the patient does so. The topic of drug-induced weight gain needs to be discussed extremely carefully with patients, though, or they may feel alarmed and stop taking their medications before a plan for replacement is in place.
3. Use the minimum dose. Drugs in the same class often aren’t interchangeable, and if no appropriate alternative to a weight-gain-promoting medication is available, providers should aim to prescribe the lowest effective dose for the shortest possible duration needed to manage the patient’s symptoms. Too often, patients are started on a medication, and then the dose and duration of the drug regimen are never reevaluated.
4. Counteract the effects with anti-obesity medication. When weight-gain-promoting medications must be used, practitioners should consider adding an anti-obesity medication, in conjunction with appropriate lifestyle modifications, to counteract weight-promoting effects in their patients with obesity. Providers who don’t feel comfortable prescribing these medications can refer their patients to an obesity medicine specialist.

The challenge of reversing weight gain

Optimizing medication choices may seem like low-hanging fruit in the effort to help patients manage their weight, and in a certain sense it is: prescribing weight-loss-promoting instead of weight-gain-promoting drugs can be a relatively simple way to prevent unwanted weight gain. This is an important strategy because reversing drug-induced weight gain is not always simple.

Jill was disappointed to find out that weight gained due to medication is sometimes no easier to lose than weight gained due to any of the other myriad contributing factors. Although switching birth control stopped the increase, she didn’t immediately lose the pounds she had gained. This is such a crucial point: many patients aren’t alarmed when realize they’re gaining weight on a medication because they assume the weight will come off easily when the medication is discontinued — however, this is often not the case. Jill and I developed a comprehensive, personalized weight-management plan that is beginning to show results, but it will be a long-term effort.

There’s no silver bullet in the fight against excess weight; obesity is a chronic disease that requires lifelong management. While weight-loss-promoting medications are a valuable addition to our armamentarium, they are not a quick fix, and pharmacotherapy needs to be part of a multidisciplinary approach that also includes diet, physical activity, and behavioral modifications. So it won’t be a surprise if most of the people who recently flocked to Ozempic without proper medical supervision regain the weight as soon as they stop taking the medication.

The ratchet nature of weight gain (easy come, decidedly not easy go) makes it even more critical that healthcare providers be aware of the potential weight-related side effects of medications and adjust their prescription choices accordingly. Obesity has many complex and interrelated causes, and the more of these underlying factors we can eliminate — like weight gain secondary to medications — the more successful we will be in helping our patients move toward a healthier weight.

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Metabolic syndrome is the name for a group of risk factors for heart disease, diabetes, and other health problems. It is often referred to as:

• Dysmetabolic syndrome
• Hypertriglyceridemic waist
• Insulin resistance syndrome
• Obesity syndrome
• Syndrome X

You can have just one risk factor, but people often have several of them together. When you have at least three of them, it is called metabolic syndrome. These risk factors include:

• A large waistline also called abdominal obesity or “having an apple shape.” Too much fat around the stomach is a greater risk factor for heart disease than too much fat in other parts of the body.
• Having a high triglyceride level. Triglycerides are a type of fat found in the blood.
• Having a low HDL cholesterol level. HDL is sometimes called the “good” cholesterol because it helps remove cholesterol from your arteries.
• Having high blood pressure. If your blood pressure stays high over time, it can damage your heart and lead to other health problems.
• Having a high fasting blood sugar. Mildly high blood sugar may be an early sign of diabetes.

The more factors you have, the higher your risk for heart disease, diabetes, and stroke is.

What causes metabolic syndrome?

Metabolic syndrome has several causes that act together:

• Overweight and obesity
• An inactive lifestyle
• Insulin resistance, a condition in which the body can’t use insulin properly. Insulin is a hormone that helps move blood sugar into your cells to give them energy. Insulin resistance can lead to high blood sugar levels.
• Age – your risk goes up as get older
• Genetics – ethnicity and family history

People who have metabolic syndrome often also have excessive blood clotting and inflammation throughout the body. Researchers don’t know whether these conditions cause metabolic syndrome or worsen it.

Who is at risk for metabolic syndrome?

The most important risk factors for metabolic syndrome are

• Abdominal obesity (a large waistline)
• An inactive lifestyle
• Insulin resistance

There are certain groups of people who have an increased risk of metabolic syndrome:

• Some racial and ethnic groups. Mexican Americans have the highest rate of metabolic syndrome, followed by whites and blacks.
• People who have diabetes
• People who have a sibling or parent who has diabetes
• Women with polycystic ovary syndrome (PCOS)
• People who take medicines that cause weight gain or changes in blood pressure, blood cholesterol, and blood sugar levels

What are the symptoms of metabolic syndrome?

Most of the metabolic risk factors have no obvious signs or symptoms, except for a large waistline.

How is metabolic syndrome diagnosed?

Your health care provider will diagnose metabolic syndrome based on the results of a physical exam and blood tests. You must have at least three of the risk factors to be diagnosed with metabolic syndrome:

• A large waistline, which means a waist measurement of
  • 35 inches or more for women
  • 40 inches or more for men
• A high triglyceride level, which is 150 mg/dL or higher
• A low HDL cholesterol level, which is
  • Less than 50 mg/dL for women
  • Less than 40 mg/dL for men
• High blood pressure, which is a reading of 130/85 mmHg or higher.
• A high fasting blood sugar, which is 100 mg/dL or higher

What are the treatments for metabolic syndrome?

The most important treatment for metabolic syndrome is a heart-healthy lifestyle, which includes

• A heart-healthy eating plan, which limits the amount of saturated and trans fats that you eat. It encourages you to choose a variety of nutritious foods, including fruits, vegetables, whole grains, and lean meats.
• Aiming for a healthy weight
• Managing stress
• Getting regular physical activity
• Quitting smoking (or not starting if you don’t already smoke)

If making lifestyle changes is not enough, you may need to take medicines. For example, you may need medicines to lower cholesterol or blood pressure.

Can metabolic syndrome be prevented?

The best way to prevent metabolic syndrome is through the heart-healthy lifestyle changes.

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