At MedShadow, we regularly interview patients about their experiences with medications. Time and time again, we have patients tell us that shortly after starting a new regimen, they gained weight. They don’t always know whether the drug directly caused their weight gain, but the timing is often suspect. Weight gain around your midsection is often associated with something called “insulin resistance,” a condition that researchers are finding more and more to be a side effect of drugs.
Take Masonia Traylor, for example, who told MedShadow she gained 40 pounds after she switched to a new human immunodeficiency virus (HIV) medication. Or, Madeleine Shonka who says she was constantly hungry after she started taking corticosteroids for her lupus. The weight she gained from eating more worsened her arthritis symptoms.
While insulin resistance doesn’t cause very many symptoms, it’s associated with weight gain, and it’s often a stepping stone toward type 2 diabetes. The earlier you address it, the better.
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What Is Insulin Resistance?
When you eat food, your body breaks that food down, and some of it becomes glucose that your cells can use to make energy. But before that happens, the glucose has to get out of your bloodstream and into your cells. That’s where insulin comes in.
Your pancreas produces insulin, a hormone which helps your cells absorb sugar, or glucose. If you have insulin resistance, your cells aren’t as sensitive to insulin, which means your pancreas has to produce more of the hormone to get your cells to open up and absorb the sugar. If you don’t produce enough insulin to shuttle all the sugar into your cells, the amount of sugar in your blood stream will start to rise because it can’t get into your cells. Over time, this can lead to diabetes.
Experts estimate that about 44% of adults in the U.S. have insulin resistance, and while the condition is tied to excess weight, only half of those with insulin resistance also have obesity. However, insulin resistance—whether or not it’s associated with obesity— raises your risk for heart attacks, strokes, nonalcoholic fatty liver disease (NAFLD), and even conditions like depression and some cancers.
How Do I Know If I Am Insulin Resistant?
Lisa Chow, MD, an endocrinologist at the University of Minnesota, says insulin resistance isn’t commonly measured at your doctor’s office and is more often used in research. There is one method that she uses in her work called the “euglycemic insulin clamp,” but it’s not something healthcare providers typically offer. It is expensive, time consuming, and invasive. You need to fast before the test. You receive continuous glucose through an IV, and your blood is tested every few minutes to see how your body is responding to it.
In some cases, doctors will use a measure called “homeostasis model assessment of insulin resistance” (HOMA IR), which is calculated using your fasting blood sugar and insulin levels. If you have both of those measures from the same recent blood test, you can plug them into an online calculator. Your HOMA IR correlates well with the insulin clamp test, but is not exact, and there is still debate among experts about what the actual cutoff for defining insulin resistance is.
Scales often suggest that if your HOMA IR is less than 1.0, you have an optimal amount of insulin sensitivity, and if your HOMA IR is over 2.5 you likely do have insulin resistance, but in between there’s a bit of a gray area. Diabetes is associated with insulin resistance, but is diagnosed based on the sugar in your blood as opposed to your HOMA IR score. Plus, the range of healthy values is likely different for people of different ethnicities, genders, and ages.
For the most part, insulin resistance does not cause symptoms, but in some cases, you may notice:
- Weight gain specifically around the midsection
- Acanthosis nigricans, or darkened, leathery patches of skin, especially on the back of the neck
Conditions Associated with Insulin Resistance
Cells in different tissues in your body, including fatty tissue, muscle tissue, and liver tissue, can develop resistance to insulin. In addition to those with diabetes and prediabetes, insulin resistance is often seen in people who have NAFLD, other metabolic disorders, or polycystic ovary syndrome (PCOS). It’s not always clear whether insulin resistance is a cause of these conditions or a symptom of them.
Pregnancy
As a result of both weight gain and hormonal changes associated with pregnancy, all women tend to develop some insulin resistance late in the pregnancy, but for some women, this sets in sooner than others and they develop a condition called gestational diabetes. Gestational diabetes—or diabetes that shows up for the first time while you’re pregnant—usually goes away after the baby is born, but it does leave you at higher risk of developing type 2 diabetes later on.
Gestational diabetes doesn’t cause many symptoms, but it’s important to control your blood sugar when pregnant to lower the risk that your baby is born prematurely. Having gestational diabetes also raises the risk that your baby will eventually develop type 2 diabetes.
The best way to prevent gestational diabetes is to exercise regularly and eat a healthy diet prior to becoming pregnant. The Centers for Disease Control and Prevention (CDC) emphasizes that you should not try to lose weight if you are already pregnant.
Fertility
Insulin resistance can make it more difficult for some women to get pregnant. It’s associated with PCOS, a condition that can prevent you from ovulating regularly. If you don’t release an egg, that egg can’t be fertilized and you won’t become pregnant.
A review of 41 clinical trials found that metformin, a diabetes drug that can help raise insulin sensitivity, can help women with PCOS get pregnant and give birth, but these women do report more gastrointestinal side effects than women who were given a placebo.
What Should I Do If I Am Insulin Resistant?
One of the reasons that doctors typically don’t test for insulin resistance—aside from the lack of noninvasive, reliable tests—is that insulin resistance isn’t something that they typically recommend treating directly.
“Really, what you want to do is treat the thing that causes the insulin resistance,” says Chow. “That’s usually fat deposition in the muscle and adipose tissue.”
Frontline therapies to address the commonly underlying issue of excess fatty tissue (which can exist even if you do not carry excess weight) are diet, exercise, and stress reduction.
Exercise to Improve Insulin Sensitivity
It’s well known that exercise can help lower blood sugar immediately after you do it, though the effect may not be long-lasting unless the exercise also leads to a reduction in your body fat. In addition to regular exercise, getting some light activity like going for a walk (even just for two minutes!) after your meals can help lower your blood sugar and prevent worsening insulin resistance. Consider taking a nightly walk after dinner to help improve your blood sugar levels.
Over time, regular exercise can help you move toward or maintain a healthy weight, which will help restore or preserve insulin sensitivity.
Diet for Insulin Resistance
Experts say the most important dietary consideration for those with insulin resistance is avoiding blood sugar spikes. You do this by making sure that you limit your intake of foods heavy in added sugars (such as soda) and simple carbohydrates (such as white bread).
Make sure meals and snacks include foods that are high in fiber and protein. For example, rather than eating pretzels as a snack, eat pretzels and hummus. Hummus is made of chickpeas which are rich in fiber and protein. Better yet, consider swapping the pretzels for carrot sticks, adding even more fiber and further minimizing the simple carbohydrates in your snack.
One study showed the Mediterranean diet in particular is effective at improving insulin sensitivity and reducing the severity of fatty liver in people with NAFLD. But the study was small, and the data is less clear for those without NAFLD.
Stress Reduction for Blood Sugar Management
Some studies link chronic levels of stress to hormonal changes that can make it harder for your body to control your blood sugar.
Check out these articles from MedShadow to see how you can reduce stress.
How to Manage Stress
Tips for Calming Work Anxiety and Beating the Sunday Scaries
8 Ways to Practice Self Care
5 Foods for Better Mental Health
Drugs that Can Treat Insulin Resistance by Raising Insulin Sensitivity
While doctors typically recommend lifestyle changes to treat insulin resistance, there are some drugs that can help, as well. Doctors often prescribe metformin, a drug initially approved for diabetes, to women with PCOS, for example, to increase insulin sensitivity. But, Chow points out that metformin often causes side effects like digestive problems.
There are a few other drugs that can help improve your insulin sensitivity including Avandia (rosiglitazone) and Actos (pioglitazone), both of which are diabetes drugs. Chow says that while these drugs don’t cause the same digestive issues as metformin, they can actually cause people to gain weight instead of losing it. Essentially, rather than having fat build up on your liver or muscle tissue, Actos and Avandia redistribute fatty tissue under your skin and away from the muscles and liver. This helps reduce insulin resistance, explains Chow, “but the overall effect is that you gain weight.”
Drugs that Can Cause Insulin Resistance
Many drugs seem to cause insulin resistance as a side effect, especially those associated with weight gain including:
HIV Medications
HIV medications have been associated with insulin resistance, weight gain and changes in weight distribution. Many people who take them lose fatty tissue around their faces and limbs while gaining it around the abdomen.
Corticosteroids
Long term use of corticosteroids at doses of more than 5 milligrams per day may cause weight gain in up to 70% of people who use them. About 20% of those who gain weight say they put on more than 20 pounds. The drugs may increase the amount of fat you store around your abdomen and increase insulin resistance.
Anti-Seizure Medications
The antiepileptic medications that cause weight gain most often are valproate (71% of patients report gaining weight) and carbamazepine (43% of patients report gaining weight). The drugs are thought to lead to increased body weight because they interact with the hormones that help you sense when you’re hungry and full. They may also slow your metabolism, and they can also raise your risk of insulin resistance and diabetes. You’re most likely to gain weight within the first year you’re taking the drug, and if you’re a woman or you carry extra weight prior to starting treatment.
Statins
Taking statins can raise your risk of developing type 2 diabetes, according to a 2023 review, and that risk increases with the dose and intensity of the statin you are prescribed. The reasons for this are unclear, but research suggests that statins may increase insulin resistance.They also appear to inhibit the pancreas’ ability to secrete insulin.
However, the extent to which the drugs contribute to new onset diabetes is hotly debated, with previous studies showing wide ranges of increased risk. Additionally, your risk is higher if you have other additional risk factors for diabetes, such as a family member having been diagnosed with the disease.
Endocrine Disruptors
Endocrine disruptors are chemicals that can distort the functioning of your endocrine system or hormones, such as insulin. Scientists are still learning about these chemicals, but we know that some of them, such as PFAS, are commonly found in the products we use and even the water we drink. Studies suggest that people with higher levels of exposure to these types of chemicals are more likely to have insulin resistance. Because the chemicals are so common, and we still have so much to learn about them, endocrine disruptors can be challenging to avoid completely, but there are some steps you can take to lower your exposure.
Supplements that May Help Improve Insulin Sensitivity
Evidence is limited, but some supplements may help you become more sensitive to insulin.
Berberine
Berberine has been referred to as “nature’s Ozempic.” It’s a plant extract often sold in capsules. Some small studies have found that it can help you lose weight, if you have a condition such as PCOS, type 2 diabetes, NAFLD, cardiovascular disease, or metabolic syndrome. However, the supplement does not seem to work the same way if you’re already healthy. It may also help with your cholesterol levels and blood pressure.
Inositol
Inositol is similar to glucose, and is often found in foods like beans, seeds, and citrus fruits. It can help manage blood sugar and regulate hormones. It is often used by women with polycystic ovary syndrome (PCOS), which can impact both fertility and insulin levels. There’s some evidence it can help with weight loss if you are overweight or struggle with obesity, though the research isn’t as strong for this as it is for controlling blood sugar.
While there are several drugs and supplements that may help reverse insulin resistance, Chow emphasizes that the most effective long term solution is focusing on lifestyle changes such as eating a diet low in sugar and simple carbohydrates, exercising regularly, and reducing stress.
“You want something durable, right? Making lifestyle changes and eating healthy is probably the most durable” solution for insulin resistance, says Chow.
