Obesity is a chronic health problem that is often progressive and difficult to treat. An estimated 80% to 90% of people with type 2 diabetes are overweight or obese. Obesity is a medical condition characterized by an excessive accumulation of body fat that poses a risk to health. It is commonly assessed using body mass index (BMI), which is a value derived from an individual’s weight and height. Having a BMI above the normal range is the leading cause of type 2 diabetes, hypertension, cardiovascular disease, stroke, arthritis and cancer.
Even a modest weight loss of 5% to 10% of initial body weight can improve insulin sensitivity, blood sugar control and blood pressure. Weight loss can also help reduce the risk of diabetes complications and improve physical functions, such as joint health and energy levels. For many people with diabetes, prevention of further weight gain is a realistic and sustainable target.
Healthy behaviour interventions are essential components of successful weight management. Interventions that combine dietary modification, increased and regular physical activity, and behaviour therapy are the most effective at improving health outcomes. Group programs and structured interprofessional programs have demonstrated great success.
Bariatric surgery may be considered for selected adults with type 2 diabetes and obesity with BMI ≥35 kg/m2 when healthy behaviour interventions – with or without weight management medication(s) – are inadequate in achieving target glycemic control or healthy weight goals.
Before discussing weight loss medication options, it is important to note that certain medications can cause considerable weight gain, for example, corticosteroids and antipsychotics. If appropriate, they should be discontinued and changed to more suitable options. Even some diabetes medications, such as glyburide, pioglitazone and older insulins, can also cause weight gain.
Other type 2 diabetes medications, such as canagliflozin and dapagliflozin, may not be indicated for weight loss but have modest weight loss as a notable side effect.
Anti-obesity treatment has historically not been particularly successful, with limited efficacy and significant adverse reactions. Some medications are associated with cardiovascular fatalities, drug dependence and suicidal ideation. Recently, newer options have been more successful in individuals with a BMI ≥30 kg/m2 or ≥27 kg/m2 with obesity-related comorbidities such as type 2 diabetes, high blood pressure, high cholesterol or obstructive sleep apnea.
Four medications are currently indicated in Canada for obesity management alongside health-behaviour changes: the older medications are naltrexone/bupropion and orlistat and the newer ‘incretin’ therapies are liraglutide and semaglutide. This article will focus on the newer medications.
The individual response to obesity management medication can differ from patient to patient. In choosing the most appropriate obesity treatment, it is important to consider potential side effects, tolerability, contraindications, drug interactions, method of administration and cost.
GLP-1 receptor agonists (incretin therapies)
Glucagon-like peptide-1 (GLP-1) receptor agonists are a family of medications that help lower blood sugar levels and promote weight loss. They work by mimicking the incretin hormone GLP-1, which is found naturally in the body. This hormone plays several roles, including triggering insulin release from the pancreas to help regulate blood sugar and slowing gastric emptying; this means the body releases less sugar from the food you eat into your bloodstream, which results in a full feeling after you eat. Specifically for weight loss, this helps by making you feel full faster and longer, and therefore eat less.
The common side effects of GLP-1 receptor agonists include gastrointestinal symptoms such as nausea, vomiting, diarrhea and constipation. It’s important to start with a lower dose and gradually increase it to minimize gastrointestinal discomfort.
Semaglutide
- Brand names: Ozempic® (for type 2 diabetes), Wegovy® (for weight loss) and Rybelsus® (for type 2 diabetes).
- Additional benefits: Improves cardiovascular health, protects the kidneys, improves sleep apnea and lowers the risk of certain obesity-related cancers.
- Usage: Semaglutide, as an injectable, comes in a prefilled, disposable pen that patients can use to self-inject once a week.
An oral form of semaglutide (Rybelsus) has been introduced, which is taken once daily, providing another option for patients who prefer oral medication over injections. It is best to take it first thing in the morning with no more than 4 ounces of water. To ensure that the medication is fully absorbed, wait 30 minutes before eating, drinking or taking other medications.
- Effectiveness: Weight loss can be approximately 12% of initial body weight at 1 year.
- Cost: Cost can vary but ranges from $250 to $400. However, depending on the indication and insurance company, special access may be obtained in order to gain coverage. Speak to your doctor or pharmacist to learn more about your options.
Liraglutide
- Brand names: Victoza® (for type 2 diabetes) and Saxenda® (for weight loss).
- Additional benefits: Can lower the risk of major cardiovascular events if there is a history of heart disease. It can also help prevent kidney problems from getting worse.
- Usage: Liraglutide comes in a prefilled pen that you can use to self-inject once daily at any time of day, without regard to food.
- Effectiveness: Weight loss can be approximately 5.4% of initial body weight at 1 year. In addition, studies have shown a 79% reduction in the risk of developing type 2 diabetes over 3 years.
- Cost Can be slightly more expensive than semaglutide, but depending on the indication and insurance company, some coverage may be available. Speak to your doctor or pharmacist to learn more about your options.
Other GLP-1 receptor agonists
Medications such as exenatide (Byetta®, Bydureon®) and dulaglutide (Trulicity®) are also available. They can support weight loss but might not be as effective as semaglutide and liraglutide in this regard.
Newer developments and research
- Mounjaro® (tirzepatide) is a once-weekly, injectable medication used to treat type 2 diabetes. It is a brand-new class of medication known as a GIP (glucose-dependent insulinotropic polypeptide)/GLP-1 agonist. It works to help with weight loss by decreasing appetite and makes people feel fuller longer, which decreases how much food is eaten. In studies, people treated with Mounjaro lost between 5.4 kg and 11.3 kg on average. Side effects include nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion and stomach pain. Mounjaro is contraindicated in individuals with a personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2 as well as in pregnancy or breastfeeding.
New drugs and combinations are continually being tested in clinical trials, with promising candidates that may offer improved efficacy and fewer side effects.
The World Health Organization has issued a warning regarding fake versions of these popular weight loss and diabetes medications. It is important not to purchase these products from unfamiliar sources.
The individual response to obesity management can differ from patient to patient. Weight loss medications are most effective when combined with lifestyle changes, including a healthy diet and regular physical activity. Healthcare providers often work with dietitians to tailor a comprehensive, individualized weight management plan. Regular follow-ups are essential to monitor progress and make any necessary adjustments to the treatment regimen.
