GLP-1 receptor agonists like Ozempic (semaglutide) and tirzepatide (Mounjaro for diabetes, Zepbound for weight loss) have gained traction in diabetes care, including use in type 1 diabetes (T1D).

Although these medications are not FDA-approved for T1D, their off-label use is increasing — particularly among individuals with overweight, obesity, or insulin resistance. Still, overall use in the T1D population remains relatively limited, despite its potential to lower A1C, reduce insulin needs, promote weight loss, and provide broader health benefits.

To better understand the real-world benefits and risks of GLP-1s, we spoke with Diana Isaacs, PharmD, CDCES, an endocrine clinical pharmacist at the Cleveland Clinic. 

 

Is there movement toward GLP-1 approval in type 1 diabetes? 

[Diana Isaacs]: Studies are underway, but nothing has been submitted to the FDA for approval yet. For example, Lilly is funding a study looking at tirzepatide in type 1 diabetes — although the focus appears to be on obesity. 

In type 1, there are also glycemic benefits, so ideally, approval would extend beyond weight management. A BMI over 27 should allow someone to qualify for a GLP-1, and many people meet that threshold — about 70% of people with T1D have overweight or obesity, which is similar to the general population.

But again, health benefits may extend beyond weight loss. 

 

What benefits are people with T1D most likely to see?  

A recent retrospective study using real-world data compared people with T1D taking these agents with those who are not — so it likely included those with and without obesity. 

The findings for those taking GLP-1s were encouraging, showing improvements in cardiovascular and kidney health. This suggests that some of the cardio-renal benefits we’re seeing in people with type 2 diabetes (T2D) may likely extend to people with T1D. 

 

What’s the thought behind “microdosing” GLP-1s? 

It’s kind of an unknown and emerging area right now, and I think that’s why the focus has been on elevated BMIs. 

The idea is that even at really low doses, GLP-1s may help lower A1C, reduce post-meal hyperglycemia, and decrease insulin needs — even in people with T1D.

Many individuals living with T1D develop some degree of insulin resistance over time. However, people at lower body weights may be more sensitive to these medications and experience side effects — even when starting on the lowest dose. 

Anecdotally, this is what I see people experiencing. 

With medications like Ozempic and semaglutide, it’s easy for people to start at a lower dose and increase slowly — because it’s available in a multi-dose pen. This can help minimize common gastrointestinal side effects like nausea, diarrhea, burping, and excessive appetite suppression. 

 

Can GLP-1s increase DKA risk in T1D? 

There is a slight increased risk, and it’s an important consideration with T1D. 

When appetite is suppressed, people may eat less and take less insulin. This can increase someone’s risk of burning fat for energy and producing ketones — even when glucose levels aren’t very high.

DKA can also occur when someone has device issues or is feeling sick, has nausea or vomiting, and isn’t hungry — so they’re not eating, and total insulin levels drop. In both scenarios, basal insulin alone may not be enough to prevent DKA.

Unlike people without diabetes, those with T1D cannot produce enough insulin to prevent full-blown metabolic acidosis.

Because of this: 

  • Glucose alone isn’t always the best indicator of DKA 
  • Ketones should be checked if you feel nauseous or have a low appetite  

 

Automated insulin delivery (AID) systems can help by adjusting basal (background) insulin, but carbohydrate ratios and correction factors will still need to be updated. For those on injections, both basal and bolus insulin doses will likely need adjustments. Because of this, there’s also an increased risk of hypoglycemia. 

 

How do GLP-1s affect insulin needs? 

GLP-1s stimulate glucose-dependent insulin release. But in type 1 diabetes, this effect is minimal or absent because beta cell function is limited. 

Instead, they work through several other mechanisms: 

  • Suppressing glucagon production, reducing the amount of glucose released by the liver 
  • Slowing gastric emptying, leading to a more gradual release of glucose into the bloodstream, less post-meal glucose spikes, and decreased mealtime insulin needs 
  • Reducing appetite, resulting in lower food intake 
  • Improving insulin sensitivity, helping the body to use insulin more effectively 

 

Excess glucagon can drive increased liver glucose production. That’s why the mechanism of lowering glucagon is thought to be a key reason for a decrease in insulin needs. 

Combined with improved satiety and more stable post-meal glucose levels, many people require less insulin overall. 

 

How do GLP-1s affect Time in Range? 

Time in Range appears to improve with GLP-1 therapy. 

Both retrospective and prospective studies — including those on tirzepatide and semaglutide — show: 

  • Increased CGM Time in Range 
  • Reduced hyperglycemia 
  • Improved glycemic variability 

 

Wearing a CGM also helps people identify and treat hypoglycemia — and guide necessary insulin adjustments. 

  

How common is GLP-1 use in T1D? 

I think it depends on where people live and who their diabetes provider is. Primary care providers may not feel as comfortable prescribing these medications as endocrinologists do. 

If I had to guess, I’d say around 5%, but I don’t know for sure. GLP-1s are becoming much more readily available and affordable through telehealth, so their use is likely to grow significantly. 

  

What does long-term data show? 

So far, long-term data looks good. 

We’ve had this class of medications since 2005, when exenatide was first approved. Current evidence shows positive benefits for cardiovascular and kidney disease. There does not appear to be an increased risk of cancer.

However, there are important considerations: 

  • Too much appetite suppression may lead to nutritional deficiencies 
  • Poor nutrition can lead to fatigue, hair loss, and muscle loss 

 

Working with a registered dietitian and your diabetes care team is essential for: 

  • Nutritional guidance  
  • Insulin adjustments 
  • Managing side effects 
  • Maintaining muscle and bone health

 

GLP-1s should be used thoughtfully, especially given the increased risk of disordered eating in T1D. 

 

Can you take metformin and a GLP-1? 

Yes, but in T1D, it’s often unnecessary to take both. Many people taking metformin are happy to stop once they start on a GLP-1 due to: 

  • Metformin’s possible ineffectiveness 
  • Fewer medications  
  • Overlapping gastrointestinal side effects 

  

What are the broader protective effects of GLP-1s? 

GLP-1 receptors are found throughout the body, which is why these medications are being studied for a wide range of conditions, including: 

  • Cardiovascular disease 
  • Kidney disease 
  • Peripheral artery disease 
  • Sleep apnea 
  • Osteoarthritis 
  • Metabolic liver disease 

 

Now the question is — are these benefits driven primarily by weight loss, or do GLP-1s offer direct physiological effects?

Research is ongoing, but the potential is significant. 

 

Wrapping it up  

GLP-1 therapies are emerging as a promising tool in type 1 diabetes. While off-label, they may help to improve Time in Range, reduce insulin needs, and offer broader health benefits. Careful monitoring and individualized support are essential as their use continues to grow.