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Rachel V Thomas

GLP-1 Drugs: Why Not Everyone Taking Ozempic May Have Lower Blood Sugar Levels

GLP-1 receptor agonist drugs such as <span>Ozempic</span> and <span>Wegovy</span> have shown significant benefits for people with diabetes and obesity. However, not everyone experiences the same results. 

Now, a study suggests that this variation may be due to genetic resistance, which means that some people are biologically less responsive to these medications, making these drugs less effective. 

The new study by scientists at <span>Stanford University</span> in the US showed that about 10 per cent of the general population carry genetic variants that lead to what the researchers called “GLP-1 resistance”. 

The GLP-1- receptor agonist drugs typically work by mimicking the hormone GLP-1 (glucagon-like peptide-1), which naturally helps regulate blood sugar by stimulating insulin release. The process slows the emptying of the stomach and reduces appetite.

However, in individuals with certain genetic variants, the team found that higher levels of GLP-1 did not regulate blood sugar better.

The researchers noted that the findings, published in the journal Genome Medicine, may be key to developing new therapies for people with GLP-1 resistance.

“There are a whole class of medications that are insulin sensitizers, so perhaps we can develop medications that will allow people to be sensitized to GLP-1s or find formulations of GLP-1, like the longer-acting versions, that avoid the GLP-1 resistance,” said Anna Gloyn, professor of pediatrics and of genetics at Stanford Medicine.

<h2>The Gene Linked to GLP-1 Resistance</h2>

<strong>Also read: </strong><a href="https://www.healthandme.com/health-news/foundayo-us-fda-approves-eli-lillys-glp-1-weight-loss-pill-article-153979432" data-type="tilCustomLink">Foundayo: US FDA Approves Eli Lilly’s GLP-1 Weight Loss Pill</a>

To zero in on the gene resistant to GLP-1 drugs, the team conducted experiments in humans. They traced this resistance to a <span>PAM</span> variant known as p.S539W.

PAM (peptidyl-glycine alpha-amidating monooxygenase) is an enzyme that is uniquely capable of activating many hormones in the body, including GLP-1.

While the researchers suspected that people with the PAM variant would have lower levels of GLP-1 in their blood, it actually increased levels of GLP-1. Although the exact mechanism is still unclear, experiments in both humans and mice confirmed signs of reduced response to GLP-1.

Analyzing diabetes drug trial data, they found that individuals with these variants were less able to lower their blood sugar levels even after six months of treatment. This suggests that despite having more circulating GLP-1, their bodies are less responsive to it. 

“When I treat patients in the diabetes clinic, I see a huge variation in response to these GLP-1-based medications and it is difficult to predict this response clinically,” said Mahesh Umapathysivam, an endocrinologist and clinical researcher at Adelaide University in Australia. 

“This is the first step in being able to use someone’s genetic make-up to help us improve that decision-making process,” he added.

<strong>Also read: </strong><a href="https://www.healthandme.com/health-wellness/can-weight-loss-jabs-surge-divorce-rates-what-experts-are-saying-article-154008485" data-type="tilCustomLink">Can Weight Loss Jabs Surge Divorce Rates? What Experts Are Saying</a>

Importantly, participants with the PAM variants did not respond differently to other common diabetes treatments, including sulfonylureas, metformin, and DPP-4i. 

The finding may help develop precision medicine, the researchers said. Knowing ahead of time who is likely to respond would help patients get on the right drugs faster, Gloyn said. 

<h2>Reasons Why Ozempic May Not Help All People Lose Weight </h2>

Ozempic is primarily indicated for type 2 diabetes management. But some doctors may prescribe it for weight loss in appropriate patients without diabetes. 

Previous research has shown that medical conditions such as sleep apnea, along with certain common medications, such as antidepressants, steroids, and contraceptives, can hamper the process of shedding extra pounds. 

Another major reason that can hamper weight loss is the side-effects of these drugs that can prompt a person to halt their prescription mid-way.

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GLP-1 receptor agonist drugs such as Ozempic and Wegovy have shown significant benefits for people with diabetes and obesity. However, not everyone experiences the same results. Now, a study suggests that this variation may be due to genetic resistance, which means that some people are biologically less responsive to these medications, making these drugs less effective. The new study by scientists at Stanford University in the US showed that about 10 per cent of the general population carry genetic variants that lead to what the researchers called “GLP-1 resistance”.  The GLP-1- receptor agonist drugs typically work by mimicking the hormone GLP-1 (glucagon-like peptide-1), which naturally helps regulate blood sugar by stimulating insulin release. The process slows the emptying of the stomach and reduces appetite. However, in individuals with certain genetic variants, the team found that higher levels of GLP-1 did not regulate blood sugar better. The researchers noted that the findings, published in the journal Genome Medicine, may be key to developing new therapies for people with GLP-1 resistance. “There are a whole class of medications that are insulin sensitizers, so perhaps we can develop medications that will allow people to be sensitized to GLP-1s or find formulations of GLP-1, like the longer-acting versions, that avoid the GLP-1 resistance,” said Anna Gloyn, professor of pediatrics and of genetics at Stanford Medicine. The Gene Linked to GLP-1 ResistanceAlso read: Foundayo: US FDA Approves Eli Lilly’s GLP-1 Weight Loss PillTo zero in on the gene resistant to GLP-1 drugs, the team conducted experiments in humans. They traced this resistance to a PAM variant known as p.S539W. PAM (peptidyl-glycine alpha-amidating monooxygenase) is an enzyme that is uniquely capable of activating many hormones in the body, including GLP-1.While the researchers suspected that people with the PAM variant would have lower levels of GLP-1 in their blood, it actually increased levels of GLP-1. Although the exact mechanism is still unclear, experiments in both humans and mice confirmed signs of reduced response to GLP-1. Analyzing diabetes drug trial data, they found that individuals with these variants were less able to lower their blood sugar levels even after six months of treatment. This suggests that despite having more circulating GLP-1, their bodies are less responsive to it. “When I treat patients in the diabetes clinic, I see a huge variation in response to these GLP-1-based medications and it is difficult to predict this response clinically,” said Mahesh Umapathysivam, an endocrinologist and clinical researcher at Adelaide University in Australia. “This is the first step in being able to use someone’s genetic make-up to help us improve that decision-making process,” he added. Also read: Can Weight Loss Jabs Surge Divorce Rates? What Experts Are SayingImportantly, participants with the PAM variants did not respond differently to other common diabetes treatments, including sulfonylureas, metformin, and DPP-4i.  The finding may help develop precision medicine, the researchers said. Knowing ahead of time who is likely to respond would help patients get on the right drugs faster, Gloyn said.  Reasons Why Ozempic May Not Help All People Lose Weight  Ozempic is primarily indicated for type 2 diabetes management. But some doctors may prescribe it for weight loss in appropriate patients without diabetes.  Previous research has shown that medical conditions such as sleep apnea, along with certain common medications, such as antidepressants, steroids, and contraceptives, can hamper the process of shedding extra pounds. Another major reason that can hamper weight loss is the side-effects of these drugs that can prompt a person to halt their prescription mid-way.

glp-1 receptor agonist  glp-1 drugs: why not everyone taking ozempic may have lower blood sugar levels

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