Are GLP-1 (Glucagon-Like Peptide-1) receptor agonists, such as liraglutide (Victoza) or semaglutide (Ozempic), safe to prescribe to individuals with a normal Body Mass Index (BMI) despite potential Gastrointestinal (GI) side effects?

From the Guidelines

GLP-1 receptor agonists like liraglutide (Victoza) and semaglutide (Ozempic) are generally not recommended for individuals with normal BMI unless they have a specific medical indication such as type 2 diabetes. These medications were primarily developed to treat type 2 diabetes and subsequently approved for weight management in people with obesity or overweight BMI with weight-related comorbidities. For individuals with normal BMI, the potential gastrointestinal side effects—including nausea, vomiting, diarrhea, and constipation—may outweigh the benefits if there is no clear medical necessity, as noted in a recent review on obesity management in adults 1. Additionally, these medications can cause excessive weight loss in normal-weight individuals, potentially leading to malnutrition or other complications. If a normal-BMI patient has type 2 diabetes that isn't adequately controlled with other medications, a GLP-1 agonist might be considered, but at the lowest effective dose with careful monitoring for weight loss and side effects, as suggested by guidelines on pharmacological interventions for adults with obesity 1. The mechanism of these medications involves slowing gastric emptying and increasing satiety by acting on receptors in the brain, which explains both their weight loss effects and GI side effects, as discussed in a narrative review of clinical pharmacology and implications for peri-operative practice 1. Any prescription should be based on a thorough risk-benefit assessment for each individual patient, considering the potential benefits and risks, including the risk of gastrointestinal adverse effects, as highlighted in a study on the clinical practice guideline on pharmacological interventions for adults with obesity 1. Some key points to consider when prescribing GLP-1 receptor agonists include:

• Gradual dose titration to minimize the risk of GI adverse effects, as recommended in the clinical practice guideline on pharmacological interventions for adults with obesity 1
• Careful monitoring for weight loss and side effects, particularly in normal-BMI patients, as suggested by a review on obesity management in adults 1
• Consideration of the potential benefits and risks, including the risk of gastrointestinal adverse effects, as discussed in a narrative review of clinical pharmacology and implications for peri-operative practice 1
• The importance of a thorough risk-benefit assessment for each individual patient, as emphasized in a study on the clinical practice guideline on pharmacological interventions for adults with obesity 1.

From the FDA Drug Label

The exposure of semaglutide decreases with an increase in body weight. However, semaglutide doses of 0. 5 mg and 1 mg provide adequate systemic exposure over the body weight range of 40-198 kg evaluated in the clinical trials.

The FDA drug label does not answer the question.

From the Research

GI Side Effects of GLP-1 Receptor Agonists

The GI side effects of GLP-1 receptor agonists, such as liraglutide and semaglutide, are a concern when prescribing these medications to individuals with a normal Body Mass Index (BMI). However, studies have shown that these side effects are generally transient and rarely lead to treatment discontinuation 2, 3, 4, 5, 6.

Safety of GLP-1 Receptor Agonists in Individuals with Normal BMI

• The safety of GLP-1 receptor agonists in individuals with a normal BMI has been evaluated in several studies, which have shown that these medications can be effective in reducing body weight and improving glycemic control in overweight or obese individuals without diabetes 4.
• A meta-analysis of 24 randomized controlled trials found that GLP-1 receptor agonists, including liraglutide and semaglutide, resulted in significant weight loss and improvements in body mass index (BMI) and waist circumference in overweight or obese individuals without diabetes 4.
• Another study found that concomitant metformin use did not increase the incidence of gastrointestinal adverse events during GLP-1 receptor agonist initiation and titration 5.

Gastrointestinal Side Effects

• The most common gastrointestinal side effects of GLP-1 receptor agonists are nausea, vomiting, and diarrhea 2, 3, 4, 5, 6.
• These side effects are generally mild to moderate in severity and often resolve on their own within a few weeks of treatment initiation 2, 3.
• A post hoc analysis of four clinical trials found that the incidence of gastrointestinal adverse events during GLP-1 receptor agonist initiation and titration was not increased in participants with concomitant metformin use 5.

Conclusion is not allowed, so the response will continue without it

Key Findings

• GLP-1 receptor agonists, such as liraglutide and semaglutide, are effective in reducing body weight and improving glycemic control in individuals with type 2 diabetes and overweight or obese individuals without diabetes 2, 3, 4.
• The gastrointestinal side effects of GLP-1 receptor agonists are generally transient and rarely lead to treatment discontinuation 2, 3, 4, 5, 6.
• Concomitant metformin use does not increase the incidence of gastrointestinal adverse events during GLP-1 receptor agonist initiation and titration 5.