on PinterestResearch has found that the effectiveness of GLP-1 drugs may vary based on a person’s genetics. Image Credit: Indranil MUKHERJEE / AFP via Getty ImagesGLP-1 medications may not always be effective for everyone.
on PinterestResearch has found that the effectiveness of GLP-1 drugs may vary based on a person’s genetics. Image Credit: Indranil MUKHERJEE / AFP via Getty Images
- GLP-1 medications may not always be effective for everyone.
- New research suggests that around 10% of people carry genetic variations that explain why.
- A new review suggests that certain combination approaches for obesity pharmacotherapy may be effective when GLP-1 drugs are not.
- Experts recommendations for alternative weight loss strategies.
GLP-1 medications have exploded in popularity to manage type 2 diabetes and treat obesity.
The popularity of this class of medications, which includes Ozempic and Wegovy, is partly due to their widespread success for weight loss.
However, new research published in Genome Medicine shows that GLP-1 drugs may not be effective for everyone. The findings suggest that certain genetic factors may offer an explanation.
Around 10% of people carry genetic variations linked to “GLP-1 resistance.” These individuals appear to have higher-than-normal levels of the hormone glucagon-like peptide-1 (GLP-1). GLP-1 helps to regulate blood sugar. In contrast, the hormone appears less effective despite higher GLP-1 levels.
“This aligns with my clinical experience, where I frequently see a variable response to GLP-1 medications,” said Mir Ali, MD, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA. Ali wasn’t involved in the study.
It’s unclear whether these genetic variations influence weight loss. GLP-1 drugs are generally prescribed at higher doses for weight loss than for diabetes management. The current study focused on how GLP-1s and these genetic variants influence blood sugar levels.
Genetic variants and GLP-1 resistance
The study focused on two genetic variants that affect the enzyme peptidyl-glycine alpha-amidating monooxygenase (PAM).
PAM plays a role in activating various hormones, including GLP-1.
Certain variants of PAM are more common in those with diabetes and may impair the release of insulin from the pancreas. The research team sought to determine whether these variants also disrupt GLP-1.
In addition to helping regulate blood sugar, GLP-1 also stimulates insulin release after meals, slows stomach emptying, and reduces appetite. GLP-1 drugs are made to mimic the effects of this hormone.
When the research team analyzed individuals with a PAM variant called p.S539W, they expected to find lower GLP-1 levels. However, they found elevated levels of GLP-1 in these individuals.
They also found that, even with higher GLP-1 levels, participants did not reduce their blood sugar levels more quickly. More GLP-1 was needed to achieve the same biological effect, indicating the participants were GLP-1-resistant.
“These findings support the idea that some patients may have partial biologic resistance to incretin-based therapies,” said Robert Glatter, MD, attending physician in the Department of Emergency Medicine at Lenox Hill Hospital in New York City, and Assistant Professor of Emergency Medicine at Zucker School of Medicine at Hofstra/ Northwell. Glatter wasn’t involved in the study.
“Still, genetics explains only a portion of treatment heterogeneity, and routine pharmacogenomic screening is not yet ready for widespread clinical use,” he added.
More research is needed to verify the
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