Excess weight is a heavy burden. It imposes physical limitations, reduces mobility, increases health risks and it’s also contrary to societal expectations that idealize a svelte body. Few people want to be obese or severely overweight, but shedding unwanted pounds remains one of life’s biggest challenges.
The demand for remedies is great. Simply browse the internet for five minutes and you will be inundated with countless suggestions for diets and exercise programs to help promote weight loss. Despite the best intentions and determination to keep off the pounds, even highly motivated people can see the scale creep upward despite their efforts. When the newest generation of prescription weight-loss drugs proved effective, therefore, it seemed like a miracle.
According to Sharleen Sidhu, MD, an endocrinologist with MarinHealth who specializes in weight management and medication research, the new drugs were discovered during clinical trials originally designed to treat type 2 diabetes.
“Weight loss was repeatedly observed as a secondary benefit,” she says. The medication proved to be clinically meaningful, thus prompting obesity-based trials as well. Researchers began using higher doses of Ozempic to promote weight loss and discovered that participants had lost 14.9% of their body mass after taking the medication for 68 weeks.
Mounjaro, approved for type 2 diabetes and marketed as Zepbound for weight loss, showed even stronger results, with a 29% average weight loss. Ozempic received FDA approval for treatment of type 2 diabetes in 2017 and is used off-label for weight loss. Wegovy is a higher dose version that the FDA approved specifically for weight management in 2021. Zepbound received FDA approval in 2023.
A balancing act
Prescription medications such as Ozempic and Zepbound are members of a class of drugs known as GLP-1, or glucagon-like peptide-1, agonists. Glucagon is a hormone produced by the pancreas along with insulin to help control blood sugar levels. Our bodies need blood sugar to be balanced in order for organs like the heart, liver, kidneys and brain to operate efficiently.
Usually, when blood sugar is too high, as it is in diabetes, the pancreas makes insulin to lower it, and when it’s too low, it makes glucagon to increase it. When the glucagon level is persistently low, it can lead to weight gain, because individuals may feel hungry and eat more to increase their blood sugar level even though they don’t need the extra calories. In such cases, GLP-1 agonists are useful, because they mimic glucagon, thus increasing the blood sugar level and reducing hunger.
Multiple mechanisms work to make GLP-1 agonists effective, and one of the main results is satiety modulation. “Medication slows down gastric emptying, and that makes you feel full sooner,” says Sidhu. At the same time, it improves glycemic control and increases glucose-dependent secretion, which helps improve metabolic health. She adds that older drugs such as naltrexone, which is used in combination with bupropion and marketed as Contrave, focus on appetite suppression.
Orlistat, another older medication that the FDA approved in 1999, prevents the absorption of a significant amount of dietary fat, thus reducing caloric intake. In addition to being a prescription medication, it is sold over the counter as Alli, a supplement that is marketed as a weight-loss aid.
Newer drugs target appetite and satiety while working in combination with lifestyle changes, while older medications usually focus on decreasing fat absorption. The approach is less effective, however, and has largely fallen out of favor.
All things considered
Obesity can have a variety of underlying causes. Family history might play a role and then “it’s like a chronic disease. You’re more predisposed,” says Sidhu. Other considerations are food intake, activity level and the environment. Metabolic issues that are uncontrolled and multiple endocrine disorders could also be factors.
Patients who are eligible for treatment typically have a body mass index (BMI) of 30, which is the threshold for obesity, or higher. Anyone with a history of medullary thyroid cancer, cardiovascular risk, substance use disorder, psychiatric illness or sleep apnea, as well as women planning pregnancy, should avoid prescription weight-loss drugs.
“All those factors should be taken into account. Overall, patient selection should be individualized,” says Sidhu, explaining that persons taking weight-loss drugs should do so only with medical supervision. She recommends consulting a licensed provider who has experience and checking in with these professionals monthly. “First and foremost, look at contraindications and evaluate baseline labs,” she advises.
Sidhu prescribes weight-loss medications that have FDA approval only. Some can be self-injected into fatty tissue just below the skin in the abdomen, upper arm or thigh, while others come in tablet form. Zepbound is administered as a once-weekly injection, with doses up to 15 mg, and studies show a 15 to 20.9% reduction in body mass at 72 weeks. Wegovy shows a 14.9% loss at 68 weeks.
Sidhu stresses that medication does not work alone and must be in conjunction with changes in diet and exercise. For medications to work, “you have to use them as an adjunct to lifestyle changes,” she says. Patients need to ensure that they get enough protein daily, and resistance training two to four times a week is important for maintaining muscle mass.
“If you lose muscle, it affects your overall metabolic health,” she explains. A nutritionist or dietitian can help one build a lifestyle foundation and make sure that an individual is getting enough protein and fiber. She advises starting with dietary changes first and increasing physical activity slowly. “You start with small, little changes, nothing too aggressive,” she says. As mobility increases, patients can go to the gym and walk regularly, gradually building up their activity level.
On the downside
Side effects can occur, and the most common are gastrointestinal, such as nausea, vomiting, diarrhea, constipation or oily stools and vitamin deficiency. More serious conditions include pancreatitis, gall bladder issues, dehydration, low blood sugar, worsening retinopathy and intestinal obstruction.
Other contraindications are dry mouth, mood changes and headache. Women should not become pregnant while taking these medications, as they are known to cause birth defects. In addition, if patients plan to undergo any procedures that require anesthesia, including colonoscopy, they need to stop taking medication a week before.
Sidhu also recommends screening an individual’s psychological status before starting treatment, as dramatic weight loss can impact a person’s identity and social dynamics.
While many people have an improved quality of life, some experience body dissatisfaction, because losing a large amount of weight tends to result in loose skin.
Older people, 65 years of age and up, have special considerations, because they are more likely to discontinue the use of weight-loss medication, either because of side effects or the high cost of prescriptions. Sidhu explains that rapid weight loss can disproportionately reduce muscle and cause patients to be more susceptible to osteoporosis, a condition in which bones become weak and are vulnerable to fractures.
If older patients are taking other medications, the addition of weight-loss drugs could promote dehydration, low blood pressure or malnutrition. Sidhu suggests starting slowly with the lowest dose and increasing the dosage less frequently. Patients should make sure their protein intake is sufficient, and resistance training is essential for maintaining muscle. Physicians should monitor older patients more closely, and if cost is an issue, they can refer them to a patient assistance program that provides medication for those who can’t afford it.
Sidhu does not recommend non-prescription medications because of the lack of FDA regulation which makes their safety and efficacy unknown. In addition, a prescription requires a doctor who can assist with medical advice and overall supervision.
Over time
Losing a large amount of weight with the help of medication is a long-term commitment, and seeing results takes patience. In certain cases, patients may see results appear in the
first couple weeks but more commonly it can take about two to four months. Sidhu reevaluates the treatment program for each patient at the end of one year and once patients have reached a desirable weight they need to embark on a maintenance program, or the lost pounds are likely to come back.
Trials show that if patients stop medication, they regain about two-thirds of the weight they’ve lost in the following year. “Once you stop, I think you need to treat obesity like a chronic disease,” she says, and she suggests strategies such as reducing the amount of medication, trying an alternative and intensifying lifestyle changes.
Using prescription medication to drop pounds is an increasingly popular method for achieving what was once a near-impossible objective, but it takes forethought and planning. “If you’re considering taking a weight-loss drug, start with a goal,” Sidhu advises. Weight is only one metric; blood pressure, mobility and joint pain matter just as much.
Body Mass Index
Body mass index (BMI) is a measurement of body fat in adults that uses height and weight to determine an individual’s category.
BMI Category BMI Range
Underweight Below 18.5
Healthy 18.5 to 24.9
Overweight 25.0 to 29.9
Obese 30.0 and above
To determine your BMI, go to https://www.nhlbi.nih.gov/calculate-your-bmi#
Source: NIH National Heart, Lung, and Blood Institute
