Weight Reduction with GLP-1 Agonists and Paths for Discontinuation While Maintaining Weight Loss

Abstract

Worldwide, nearly 40% of adults are overweight and 13% are obese. Health consequences of excess weight include cardiovascular diseases, type 2 diabetes, dyslipidemia, and increased mortality. Treating obesity is challenging and calorie restriction often leads to rebound weight gain. Treatments such as bariatric surgery create hesitancy among patients due to their invasiveness. GLP-1 medications have revolutionized weight loss and can reduce body weight in obese patients by between 15% and 25% on average after about 1 year. Their mode of action is to mimic the endogenous GLP-1, an intestinal hormone that regulates glucose metabolism and satiety. However, GLP-1 drugs carry known risks and, since their use for weight loss is recent, may carry unforeseen risks as well. They carry a boxed warning for people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Gastrointestinal adverse events (nausea, vomiting, diarrhea) are fairly common while pancreatitis and intestinal obstruction are rarer. There may be a loss of lean body mass as well as premature facial aging. A significant disadvantage of using these medications is the high rate of weight regain when they are discontinued. Achieving success with pharmacologic treatment and then weaning to avoid future negative effects would be ideal.

Keywords: GLP-1 receptor agonists; adverse effects; appetite regulation; body weight; drug therapy; energy balance; treating obesity.

Figure 1

Consequences of obesity-induced inflammation. Obesity leads to a physiological inflammatory response, such as oxidative stress, as illustrated by the hypertrophic adipocytes secreting pro-inflammatory cytokines, cardiometabolic conditions, and MALSD. These conditions increase the risk of mortality long-term which is generally associated with obesity.

Figure 2

Adverse effects of GLP-1 class drugs. Gastrointestinal issues are common, ranging from nausea and diarrhea to rarer and more severe consequences such as pancreatitis. Rapid weight loss due to the use of GLP-1 drugs is associated with biliary disease, sarcopenia, and alopecia. Rapid weight loss can also lead to what is known as an “Ozempic face”, where the cheeks become hollowed out, and wrinkles, as well as eye bags, become more pronounced.