Are Glucagon-like peptide (GLP) agonists more effective for weight loss in individuals with Diabetes Mellitus (DM) and a Body Mass Index (BMI) greater than 30?

From the Guidelines

GLP-1 agonists are the most effective pharmacological agents for weight loss in individuals with diabetes and a BMI greater than 30, with semaglutide and tirzepatide being the preferred options due to their greater weight loss efficacy and added weight-independent benefits. These medications have been shown to produce significant weight loss, with clinical trials demonstrating that patients with diabetes and obesity can lose approximately 10-15% of their body weight with semaglutide and up to 20% with tirzepatide over 68 weeks of treatment 1. The enhanced effectiveness of GLP-1 agonists in this population is likely due to their ability to address multiple mechanisms simultaneously, including improving insulin sensitivity, reducing appetite, slowing gastric emptying, and regulating blood glucose levels.

Key Considerations

• GLP-1 agonists should be used alongside lifestyle modifications, including calorie reduction and increased physical activity, for optimal results 1.
• Side effects commonly associated with GLP-1 agonists include nausea, vomiting, and diarrhea, which typically improve over time 1.
• Most GLP-1 agonists are administered as weekly injections, though some require daily dosing, and should be titrated gradually to minimize gastrointestinal side effects 1.
• The preferred pharmacotherapy for people with diabetes and overweight or obesity should be a glucagon-like peptide 1 receptor agonist or dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist with greater weight loss efficacy, such as semaglutide or tirzepatide 1.

Clinical Implications

• Weight management pharmacotherapy should be considered for people with diabetes and overweight or obesity, along with lifestyle changes, and the potential benefits and risks must be considered 1.
• Weight management pharmacotherapy indicated for chronic therapy should be continued beyond reaching weight loss goals to maintain the health benefits, as sudden discontinuation often results in weight gain and worsening of cardiometabolic risk factors 1.

From the FDA Drug Label

The mean BMI was 33.9 kg/m 2. Treatment with liraglutide injection as add-on to metformin and rosiglitazone produced a statistically significant reduction in mean HbA1c compared to placebo add-on to metformin and rosiglitazone. The mean age of participants was 55 years, and the mean duration of diabetes was 9 years. Both treatment groups had a mean decrease from baseline in body weight of approximately 3 kg

The GLP-1 agonist liraglutide is effective at weight loss in those with diabetes and BMI greater than 30, with a mean decrease from baseline in body weight of approximately 3 kg. However, the effectiveness of GLP-1 agonists in general for weight loss in this population cannot be directly concluded from this data. 2

From the Research

Efficacy of GLP-1 Agonists in Weight Loss for Patients with Diabetes and BMI > 30

• The efficacy of GLP-1 agonists in weight loss for patients with diabetes and a BMI greater than 30 has been evaluated in several studies 3, 4, 5, 6, 7.
• Studies have shown that GLP-1 agonists, such as liraglutide and semaglutide, can achieve significant weight loss in patients with obesity, regardless of diabetes status 3.
• A systematic review and meta-analysis found that semaglutide had a greater mean weight loss compared to liraglutide and dulaglutide in patients with type 2 diabetes 4.
• Another study found that the efficacy of GLP-1 agonists in reducing body weight and waist circumference was greater in patients without type 2 diabetes mellitus (T2DM) and those with a high body mass index (BMI) or longer treatment cycles 7.

Comparison of Different GLP-1 Agonists

• A network meta-analysis compared the efficacy and safety of seven GLP-1 receptor agonists and polyagonists for weight loss in patients with obesity or overweight 7.
• The analysis found that retatrutide and tirzepatide exhibited superior efficacy compared to other GLP-1 receptor agonists and polyagonists in reducing body weight and waist circumference 7.
• Semaglutide and liraglutide have also been shown to be effective in reducing body weight and improving cardiometabolic risk factors in patients with type 2 diabetes 5.

Safety and Adverse Events

• Common adverse events associated with GLP-1 agonists include gastrointestinal symptoms, such as nausea and diarrhea 3, 4, 6.
• Real-world studies have shown that patients with type 2 diabetes or obesity who use GLP-1 agonists may experience frequent gastrointestinal disturbances, but no clear increase in risks of severe events like pancreatitis or pancreatic cancer, thyroid disorders, or depression and self-harm 6.
• The incidence of adverse events was higher in patients without T2DM, but there was no significant difference in the incidence of adverse event withdrawal for all interventions in head-to-head comparisons 7.