Editor’s Note: T1D Exchange and the author are not medical professionals. They do not endorse any specific therapy or brand described herein, which are provided for informational purposes only; GLP-1 therapy is currently not FDA-approved for T1D management. Always consult your health care provider for the proper care and treatment of your T1D.  

*Other reading: Our Experience Taking GLP-1 Medications in T1D and Six Dysfunctional Hormones of Type 1 Diabetes. 

With all the media coverage surrounding Ozempic and Trulicity (GLP-1 agonists) and Mounjaro (a dual GIP-GLP-1 agonist) – I turned to Dr. Claresa Levetan, MD to help explain how these medications work in type 1 diabetes (T1D).

Intended to treat type 2 diabetes (T2D) and obesity, endocrinologists are increasingly prescribing GLP-1s off-label for people with T1D. At the moment, there are a handful of active/pending/completed studies on the use of GLP-1 medications in T1D.

First, what are these medications? 

The medications are making headlines for their impact on weight-loss, appetite suppression, insulin sensitivity, and more. While mainstream media is portraying these medications as easy shortcuts, they serve a significant purpose for those who truly need them. 

We refer to these medications throughout this article: 

GLP-1 agonists:  

  • glucagon-like peptide-1 agonist 
  • semaglutide (Ozempic, Wegovy, Rybelsus), dulaglutide (Trulicity), and Exenatide (Byetta) 
  • Ozempic, Wegovy, Trulicity, and Byetta are taken via once-weekly injection 
  • Rybelsus is taken once daily via orally swallowed pills 

GIP-GLP-1 agonists:  

  • glucose-dependent insulinotropic polypeptide & glucagon-like peptide-1 
  • tirzepatide (Mounjaro) 
  • Mounjaro is taken once weekly via injection 

Let’s take a closer look at how they work and why they might benefit people with T1D. 

Your gut and liver glucose with T1D 

In a person without T1D, specialized cells in the small intestine naturally secrete the hormones GLP-1 and GIP while eating. GLP-1 and GIP have receptors within the pancreatic islets, and they play a role in suppressing glucagon — a hormone that tells the liver to release stored glucose throughout the day — during and after meals.   

In people with T1D, however, your beta and alpha cells are destroyed by the autoimmune attack of your disease. The GLP-1 and GIP hormones now have nowhere to go in the pancreas and can’t do their jobs with the alpha and beta cells.  You’ve been prescribed insulin to replace only a portion of the   beta-cell function, and nothing for your alpha cell function, except emergency-only glucagon.  

Many people with T1D are simply unaware of, extremely used to, or struggling with the metabolic chaos that follows, including: 

  • Your liver is producing more than normal amounts of glucose 
  • Your brain doesn’t receive normal cues of fullness after eating  
  • You need more insulin to manage glucose levels  

We need more insulin because our liver produces more glucose than it would if we did not have T1D. This excess glucose and excess insulin can also make it harder to manage our weight, appetite, insulin needs, and blood glucose levels. 

Potential benefits and side-effects of GLP-1 medications in T1D 

In those of us living with T1D, introducing a GLP-1 medication can: 

  • suppress liver glucose production during and after meals 
  • suppress overall liver glucose production 
  • increase how full you feel during/after eating 
  • increase your overall sensitivity to insulin 
  • slow down how quickly your stomach digests food 
  • decrease your overall appetite, hunger cues, and food cravings 
  • decrease your overall basal and bolus insulin needs 

Because GLP-1 medications remain in the bloodstream longer than native GLP-1, they reach the other organs involved in metabolism, including the liver, stomach, intestinal tract, and brain.  

Based on recent studies in those with T2D, GLP-1s have been shown to also benefit memory, reduce cardiovascular disease risks, increase bone mass, and preserve liver and kidney function. These benefits are highly likely to translate directly to those with T1D, who already face a higher risk of health challenges in these categories. 

*Read: Our Experience with GLP-1 Medications & Type 1 Diabetes 

Research on the use of GLP-1 medications in T1D 

At the Harvard Medical School Clinical Endocrinology 2022 meeting, the use of GLP-1 medications in T1D was discussed after several of the diabetes lectures. Many endocrinologists admitted to using GLP-1 receptor analogs off-label for people with T1D in their practice, including Dr. Levetan.  

Weight loss helps improve insulin resistance in T1D, and an early study demonstrated that when the liver’s glucose production is suppressed in T1D, insulin doses for meals are lowered, too.  

Newer analogs, such as semaglutide (Ozempic), have not only proven to lower A1C levels in people with T2D, but they also lower the risk for major cardiovascular events — such as stroke, heart attack, or death among those with known heart disease.  

But until larger randomized prospective trials occur among different populations of T1D patients, such as new onset and those with long-existing T1D, the long-term benefits of GLP-1 receptor analogs are not yet fully known. The data is pending on tirzepatide (Mounjaro) — a dual GIP-GLP-1, and the first of its kind on the market. 

GLP-1 medications have also been shown to increase overall time-in-range (TIR) in a person with T1D based on CGM data. Although greater TIR doesn’t necessarily translate to a lower A1C, it does usually mean far fewer extreme blood glucose swings and, therefore, fewer long-term complications.  

Clearly, by increasing TIR, GLP-1 medications can lessen the hour-to-hour burden of managing blood glucose levels to improve a person’s overall quality of life: fewer alerts, alarms, corrections, and decisions. 

Things to consider when using GLP-1 medications in T1D 

Because T1D requires basal and meal insulin, a tailored approach to GLP-1 adjunctive therapy is necessary. Dr. Levetan explained that GLP-1s themselves do not cause hypoglycemia, instead they reduce a person’s need for insulin.  

When starting a GLP-1 medication, a person with T1D should work very closely with their healthcare team to fine-tune insulin doses at the start and throughout GLP-1 therapy. When adjustments — primarily reductions — in both basal and bolus insulin doses are made in a timely manner, the risk of hypoglycemia is reduced.  

For example, when used to treat obesity without diabetes, there is no noticeable impact on blood glucose levels. But in people already taking insulin or other glucose-lowering therapies, immediate and gradual adjustments to a person’s mealtime insulin doses will likely be necessary.  

Dr. Levetan shares the following guidelines: 

  • Very slow titration of the GLP-1 in people with T1D is recommended, much slower than the standard dosing prescribed for T2D. Gradual titration helps manage potential digestive side effects and the reduced insulin needs. 
  • A corresponding reduction in insulin therapy must accompany the GLP-1 titration, especially the premeal insulin bolus. 
  • Emergency glucagon should be prescribed to any T1D starting GLP-1 therapy in the event of severe hypoglycemia while gradually fine-tuning insulin doses. 
  • GLP-1 brand selection is based on the patient’s health history and current comorbidities, due to formula variability. Considerations include: 
  • existing gastroparesis 
  • existing retinopathy 
  • thyroid cancer history 
  • past/current pancreatitis 
  • renal dysfunction 
  • biliary dysfunction 

GLP-1 therapy, if helpful in an individual, may also be a “forever” therapy like insulin, which must be considered. If one brand isn’t producing the desired benefits, another GLP-1 trial may make sense.  

In clinical practice, Dr. Levetan now prefers dual GIP-GLP-1 therapy for her T1D and T2D patients; but ultimately the selection depends on insurance coverage. Tailored approaches increase the safety of the T1D patient, decrease side-effect severity, and increase therapy compliance. Patients and health care providers must discuss all the options honestly.  

The biggest hurdle: insurance coverage 

People with T1D are demanding better therapies than insulin alone. In the U.S., insulin and pramlintide are the only authorized replacement for the six hormones our bodies don’t produce properly. 

The FDA has not approved GLP-1 therapy for T1D. Yet with a tailored approach using CGM, health care providers and T1D patients are successfully and safely using these adjunctive therapies off-label. With reduced insulin needs, increased TIR, and potential multi-organ benefits, GLP-1 therapies can improve quality of life, morbidity, and mortality risks in those living with T1D. 

Getting insurance coverage for GLP-1 and GIP-GLP-1 medications for T1D is increasingly challenging. As the demand for these expensive medications increases, the rejections for coverage appear to be increasing, too. 

 The healthcare provider is left to advocate on behalf of the patient via prior authorizations, letters of medical necessity, and creative diagnosis coding. Considering many people with T1D struggle with weight gain, insulin resistance, incessant hunger, and post-meal blood glucose swings, the argument for GLP-1 therapy in T1D is strongly supported. 

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