The Obesity Epidemic

Obesity represents one of the most common diseases in developed countries around the world. Within just a ten-year span from 1990 to 2000, the United States saw obesity rates increase from 23% to 31%. The prevalence of obesity has since risen even higher, and between 2017 and 2018 roughly 42% of Americans were categorized as being obese. In addition, the incidence of severe obesity sits at roughly 9% of Americans.

The obesity epidemic within the U.S. is both shocking and concerning. Obesity is linked to conditions such as type II diabetes mellitus (T2DM), heart disease, stroke, and cancer. These conditions represent chronic and potentially debilitating diseases with a high morbidity and mortality burden. Likewise, obesity is one of the most common causes of preventable and premature death. In fact, the American Medical Association (AMA) declared obesity as a chronic disease in 2013. This designation only further emphasizes its complexity, as obesity is caused by multi-factorial involvement of genetics, environment, and lifestyle.

Obesity is not just a health concern. The medical cost associated with obesity in 2008 was roughly $147 billion in the U.S. This cost has likely risen over the past decade, representing an enormous economic burden. On average, the medical costs of an obese individual is $1,429 more than that of someone of a normal weight.

Obesity and Diabetes: A Deadly Link

As aforementioned, obesity can cause a slew of health problems. One of these includes the development of diabetes, specifically type II diabetes. T2DM occurs when the body does not produce enough insulin, a hormone important to blood sugar regulation. While those with T2DM can sometimes control their blood sugar with diet and exercise alone, many others will require medication such as insulin to keep their diabetes under control.

The specific causes of diabetes are not fully known, but we are aware of various factors that can increase your likelihood of developing diabetes. Being overweight or obese represents a modifiable, preventable risk factor for developing diabetes. Overweight is defined as a body mass index (BMI) of 25 or greater. Obesity is defined as having a BMI of 30 or more.

More than 90% of individuals with T2DM have a BMI of 25 or greater. Because of how prevalent concomitant disease is amongst individuals, most providers will have patients with comorbid obesity and diabetes. But why is obesity associated with the development of diabetes? There are a few reasons as to why this may occur.

Alterations to fat metabolism

Being overweight can disrupt how our body metabolizes fat. These alterations to metabolism cause adipose (fat) tissue to release fat molecules into the blood. This phenomenon changes how our body responds to insulin, which is a critical process to regulating blood sugar. Your body can produce less insulin or can become less sensitive to insulin.

Inflammation

Inflammation is the root cause of many diseases, including obesity. Research demonstrates that abdominal fat induces the release of inflammatory substances. These inflammatory substances, known as adipokines, also disrupt the insulin pathway. Adipose tissue produces too many adipokines, leading to insulin resistance.

Additionally, obesity causes an overproduction of another substance called chemokines. With release of chemokines, macrophages are activated. Macrophages are cells involved in the inflammatory process. These macrophages can lead to cytokine production and downstream reductions in insulin sensitivity.

Preventing and Treating Diabetes Through Weight Loss

Weight loss is a key component to both preventing and treating diabetes. Research demonstrates that behavioral counseling, weight loss programs, and consistent medical support can improve outcomes in overweight individuals with diabetes. The main ways through which patients can lose weight include:

  1. Reducing caloric intake
  2. Increasing physical activity
  3. Taking weight loss medications in addition to diet, exercise, and appropriate therapeutic management of diabetes

Individuals with newly diagnosed diabetes will typically start by trying to control their blood sugar and weight with diet and exercise alone. Typically, a weight loss of three to five percent of someone’s original weight can improve blood sugar control and hemoglobin A1C (a lab value important to understanding glucose control). A modest weight loss can slow the progression of diabetes and lessen the need for medications to lower blood sugar.

Clinicians will typically target a five to ten percent loss of body weight as an initial treatment goal. A loss of weight within this range correlates to a 0.6 to 1% decrease in A1C in addition to other health benefits. However, even a lower weight loss of two to five percent can induce a clinically meaningful benefit. For those with prediabetes, the American Diabetes Association (ADA) suggests a seven percent loss in baseline body weight to prevent diabetes.

While adequate nutrition and physical activity alone can often support weight loss goals, weight loss medication can be helpful for certain individuals. The rest of this article will focus on what weight loss medications are available to treat obesity and diabetes.

Weight Loss Medications

Although healthy lifestyle changes can provide massive benefits to obese and diabetic patients, some will require medications to assist in weight loss. For certain patients, physicians may consider changing their diabetic therapy and incorporating weight loss drugs.

To start, providers should consider the below antidiabetic drugs that lower blood sugar levels. Some of these medications may also aid in weight loss. The following drugs are considered good options to start with:

  • Metformin
  • Pramlintide
  • Glucagon-like peptide 1 (GLP-1) receptor agonists
  • Sodium–glucose cotransporter 2 (SGLT2) inhibitors
  • Dipeptidyl peptidase 4 (DPP-4) inhibitors

Metformin use has demonstrated a weight loss of six pounds. Therapy with pramlintide can cause an eight-pound weight reduction in addition to also reducing daily insulin requirements in those requiring insulin. GLP-1 agonists are the most beneficial in terms of weight loss, and will be discussed in further detail in this article. DPP-4 inhibitors do not generally affect weight.

Patients should avoid therapy that is associated with significant weight gain. Examples of antidiabetic drugs that can cause weight gain include:

  • Thiazolideniones (e.g., pioglitazone and rosiglitazone)
  • Insulin
  • Sulfonylureas (e.g., glimepiride, glyburide, and glipizide)

Additionally, patients should avoid classes of medications that can cause weight gain or increased appetite. Examples of these medications include:

  • Steroids
  • Antihistamines
  • Some selective serotonin reuptake inhibitors (SSRIs)
  • Beta blockers
  • Antipsychotic agents

GLP-1 Receptor Agonists

GLP-1 receptor agonists are a great class to start with as they demonstrate both glucose-lowering and weight loss effects. Specifically, GLP-1 modulating agents are associated with an 11- to -12-pound loss in weight. This weight reduction is significantly greater than other antidiabetic medications.

This class of drugs works like a hormone in the body known as glucagon-like-peptide (GLP-1). This hormone regulates one’s appetite and hunger. Therefore, these medications control appetite, causing individuals to eat less calories and lose weight.

Examples of GLP-1 receptor agonists include Ozempic, Saxenda, Trulicity, and Rybelsus.

Ozempic

Ozempic is indicated for adults with T2DM in addition to diet and exercise to lower A1C and normalize blood sugar levels. It can also decrease one’s risk of serious cardiovascular (CV) events like stroke, heart attack, or death in those with heart disease.

Ozempic is also proven to help individuals with T2DM lose weight. In a one-year clinical trial, participants taking Ozempic lost and average of 12 pounds. In another study, Ozempic was compared with Trulicity in terms of weight loss. At comparable doses, Ozempic resulted in an almost two times greater reduction in weight compared with those on Trulicity.

Saxenda

Saxenda is an injectable medication indicated for:

  • Adults with a BMI of 27 or greater with a weight-related medical condition or obesity
  • Children ages 12 to 17 years old that weigh over 132 pounds and are obese

For these patients, Saxenda can help to lose weight and keep weight off when used with a diet and exercise plan. In a study of over 3,700 patients, 85% of patients on Saxenda lost weight. Roughly 60% of individuals achieved a weight reduction of at least 5%, and 33% of individuals achieved a weight reduction of at least 10%. Finally, about 6% of participants lost over 20% of their baseline weight. About half of the individuals enrolled in this trial had sustained their weight loss three years after taking Saxenda.

Trulicity

Trulicity is a weekly injectable prescription medication that can help regulate blood sugar in those with T2DM. It can also lessen the risk of cardiovascular problems like heart attack, stroke, or death in those with heart disease.

Trulicity is not indicated for weight loss, however, it may provide some beneficial effects on weight. For example, one study demonstrated an average weight loss of 6.6 pounds with the 1.5 mg dose and an average weight loss of 10.1 pounds with the 4.5 mg dose (8).

Rybelsus

Rybelsus is another diabetes medication that can improve blood sugar when used with proper diet and exercise. Rybelsus is not indicated for weight loss but can help in shedding a few pounds. In one study, participants had an average loss of 4.8 pounds on the 7 mg dose. Those on a higher dose of 14 mg had an average loss of 6.8 pounds.