Medically reviewed by Anna Goldman, MD.

By now, everyone knows that new drugs like Ozempic and Mounjaro are perhaps the most effective drugs ever developed for type 2 diabetes and obesity. Less attention has been paid to their potential to help people with type 1 diabetes. 

Satish Garg, MD, has a bold prediction: “I have no doubt in my mind: Going forward, this class of drugs is going to be used by the vast majority of people with type 1 diabetes.”

Dr. Garg, a professor at the University of Colorado’s Barbara Davis Center for Diabetes, has authored two recent studies on the real-world use of GLP-1s to treat type 1 diabetes in people who are also overweight or have obesity: one on semaglutide (Ozempic, Wegovy) and one on tirzepatide (Mounjaro, Zepbound), which is technically a GLP-1/GIP agonist. They show these blockbuster drugs can have exceptional benefits, including massive weight loss and significant blood sugar reductions.

Eventually, however, Garg thinks that almost everyone with type 1 diabetes will be using a GLP-1, even people who are not overweight: “There are benefits above and beyond weight loss, even in individuals with normal BMI [body mass index].”

“Smaller doses of these drugs will be used routinely in people with diabetes, not because of weight loss, but because of the long-term benefits they might give — cardiovascular disease and kidney disease — and because glycemia is significantly improved.”

GLP-1 drugs are not currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of type 1 diabetes — and they may never be. But a growing number of clinicians are prescribing them off-label, principally to people with type 1 who are overweight or have obesity.

Type 1 Diabetes, Overweight, and Obesity

The classic stereotypical type 1 diabetes patient is a child who is thin or even emaciated. Acute hyperglycemia, the signature feature of undiagnosed or uncontrolled diabetes, prevents the body from harvesting energy from food; eventually, the body will start burning body fat and muscle for fuel, leading to unexplained weight loss, among other symptoms.

Thankfully, that stereotype is now largely obsolete, at least in the developed world. Modern insulin and glucose measurement technology allow people with type 1 diabetes to live longer and healthier lives. For better or worse, it is also now far easier to eat a standard diet, which means that people with type 1 have increasingly begun to resemble their nondiabetic peers. One downside to the shift is that excessive weight gain is now just about as prevalent in the type 1 diabetes population as it is in the general population.

The health changes associated with overweight and obesity can have negative consequences for both short-term glucose management and long-term health. “People with type 1 diabetes have the same troubles as people with type 2,” says Garg, including “weight gain, insulin resistance, cardiovascular disease, and kidney disease.” In some cases, patients will develop double diabetes. 

In short, people with type 1 diabetes need effective obesity treatment just as badly as other adults do.

Semaglutide, Tirzepatide, and Type 1 Diabetes: The Data

Garg’s recent studies evaluated the real-world use of GLP-1s prescribed to people with type 1 diabetes at the Barbara Davis Center. At the moment, the use of such drugs is almost exclusively limited to people with a clear medical need to lose weight.

The tirzepatide analysis evaluated participants with an average age of 40 and an average diabetes duration of 24 years. At the beginning of the study, their average weight was 229 pounds. Most were white and female.

Tirzepatide appeared to trigger major metabolic improvements across the board:

Extraordinary weight loss: After one year, the average participant had lost 18.5 percent of their body weight, a whopping 46.5 pounds. Some of the patients lost as much as 200 pounds.
A1C improvement: The average A1C dropped 0.67 percentage points. Average blood sugar levels dropped by 23.5 mg/dL.
More time in range: Participants spent an additional 15 percent of their day within the target glucose range.
Fewer glucose excursions: Standard deviation, a measure of the amplitude of blood sugar swings, declined significantly.
Lower insulin doses: Volunteers required far less insulin, an average of 24.7 fewer units per day. Basal doses declined by about 10 units, bolus insulin by about 15 units.

“The benefits are unbelievable,” says Garg. “It really flattens all the glucose excursions.” And the weight loss was beyond his expectations.

Garg’s earlier trial of semaglutide also identified comprehensive improvements, including weight loss, better A1C, and increased time-in-range. The results were not quite as impressive, though, particularly when it comes to weight loss: Semaglutide users lost only an average of 16 pounds.

But GLP-1s Carry Serious Risks for People With Type 1 Diabetes

Despite the marvelous results, there’s a reason why experts are very cautious about recommending the use of semaglutide and tirzepatide for people with type 1 diabetes. These powerful drugs carry very real risks for people with the condition. The drugs need to be managed in a unique way, using a new strategy that experts have not quite agreed on yet.

 There are two deadly obstacles that all people with type 1 diabetes constantly need to navigate around: the threats of severe low blood sugar (hypoglycemia) and diabetic ketoacidosis (DKA). GLP-1 drugs are suspected to raise the risk of each.

GLP-1s and DKA

GLP-1s have quickly become legendary for their bad gastrointestinal side effects. At its highest dosage, for example, semaglutide causes diarrhea in 32 percent and vomiting in 25 percent of users.

For most people, these side effects disappear as their bodies become accustomed to the medication. But the risks are sharply elevated for people with type 1 diabetes, because dehydrating illnesses like vomiting and diarrhea can lead rapidly to DKA. And Garg fears that these tummy troubles may be even more common in people with type 1 diabetes.

DKA is ultimately caused by a critical lack of insulin, which causes all manner of hormone and electrolyte imbalances; the blood becomes an acidic poisonous cocktail, and the condition is fatal without emergency treatment. This blood acidification both causes dehydration and is accelerated by dehydration. And when people with type 1 diabetes cannot eat or drink due to a stomach ailment, they will inevitably use less insulin, which only makes DKA even more likely to develop.

The fear of DKA requires people with type 1 diabetes to be especially cautious with GLP-1 medications.

GLP-1s and Hypoglycemia

On the other hand, GLP-1s can increase the risk of severe low blood sugar events because they radically impact insulin requirements. Most people with diabetes who take an injection of a GLP-1 drug will experience enhanced insulin sensitivity almost overnight. GLP-1s themselves do not often cause hypoglycemia; in fact, they work in a glucose-dependent manner, preventing blood sugar spikes after meals. But if users with type 1 diabetes do not rapidly adjust their insulin usage, they are at risk of using too much and plunging their blood sugar down to unsafe levels.

At the Barbara Davis Center for Diabetes, Garg instructs his patients to reduce their insulin by 20 percent when they start a GLP-1 for the first time. He and his colleagues continued to suggest changes as the study went on and participants stepped up to higher GLP-1 dosages.

Nobody in the study was hospitalized with severe low or high blood sugar. But Garg has had some scary experiences with his own patients who overcompensated and began taking even less insulin than he advised “because they were scared of getting hypoglycemia. And that results in a high risk of DKA.”

Garg took the potential dangers seriously: “We closely monitored these patients.” All participants wore a continuous glucose monitor (CGM), allowing doctors to remotely follow their blood sugar levels. None of the participants experienced severe hypo- or hyperglycemia.

Nevertheless, Garg remains “absolutely” worried about the use of GLP-1s in less carefully controlled circumstances. “I am definitely worried that these drugs are going to be used left and right in people with type 1 diabetes.”

People With Type 1 Diabetes Need Smaller GLP-1 Doses

The best way to manage these two risks, Garg believes, is to take smaller doses of GLP-1 medications in the first place. Smaller doses and more gradual dose escalation schedules can soften the impact and reduce the severity of side effects and insulin requirement changes. 

That’s easier said than done. Ozempic, Mounjaro, and other injectable drugs in this family are manufactured and distributed in precise, discrete doses that were not designed for the more sensitive bodies of people with type 1 diabetes. But there are ways of injecting less medication than the manufacturers intended.

A starter dose of Ozempic, for example, is 0.25 milligrams (mg) per week. But Garg thinks that’s far too much for most people with type 1: “We would start them on 0.1 mg and then gradually over three months build them up 1 or 2 mg per week.” It is possible to draw up smaller doses of semaglutide by counting clicks on the delivery pen, a technique that neither the FDA nor the manufacturer endorses.

Tirzepatide comes in a pen device that does not allow for custom dosing in the same way. For smaller tirzepatide doses, Garg will sometimes ask his patients to take a dose every 10 days rather than every 7. Some of his patients go further and extract precise smaller doses of tirzepatide from the pen using an insulin syringe — a technique that Garg does not recommend.

Smaller doses aren’t necessarily just for the initial months of treatment. Clinicians might be wise to keep patients with type 1 on smaller GLP-1 doses throughout their treatment. At the Barbara Davis Center, very few of the study participants who had been prescribed tirzepatide ever progressed to the higher available doses. The mean tirzepatide dose in use at the end of the trial was about 10 mg (the third-largest dose available), and, after one year, only 6 of 62 participants used the highest available weekly dose (15 mg). And people with less weight to lose have even less need of large doses.

The need for smaller doses is most critical for children using these drugs. Garg insists that many doctors and endocrinologists are already prescribing GLP-1s to children who are overweight and have type 1 diabetes, despite a complete lack of study or official guidance on the issue. Children have smaller bodies, of course, but adolescence can also be a particularly challenging time for blood sugar management. Hormonal changes tend to introduce dramatic shifts in insulin sensitivity, making it even more important to proactively manage risk. (Semaglutide is approved for weight loss in adolescents ages 12 and up, though there is some controversy over how frequently they should be prescribed.)

New Guidelines Are Needed

Garg states that the use of GLP-1s to treat type 1 diabetes is already quite common. But there’s no telling if they’re being prescribed and used safely in the real world: “The providers really don’t know how to use these drugs properly. All of the guidelines need to be written.”

In a recent editorial for Diabetes Technology & Therapeutics, Garg and his colleagues shared their best practices for the safe and effective use of GLP-1s in people with type 1 diabetes. Here are some of the most significant takeaways for clinicians:

Reduce insulin dose by 20 to 30 percent when initiating GLP-1 treatment.
Adjust insulin doses when patients step up to larger GLP-1 doses.
Titrate GLP-1 doses more slowly than the manufacturers recommend, stepping up every two or three months rather than monthly.
Patients can “count clicks” to use smaller doses of semaglutide.
Patients can use tirzepatide less frequently than every seven days.
Make sure that patients have glucagon rescue medication at home.
Instruct patients to test ketone levels regularly.

Though these recommendations are based on solid clinical experience, Garg and his colleagues are still just making educated guesses about a largely unstudied phenomenon. There have been plenty of studies on older, less powerful drugs in the GLP-1 class, such as liraglutide, but semaglutide and tirzepatide represent new territory.

“The proper studies need to be done to learn the best way to use these drugs, which are definitely needed in people with type 1 diabetes.”

Do You Need to Take GLP-1s Forever?

It is widely believed that GLP-1s must be used indefinitely or the benefits will go away.

At the Barbara Davis Center, hundreds of patients with type 1 have used a GLP-1 medication and lost weight. Of the many who have ceased to use the drug, only three have been able to keep the weight off. In all likelihood, semaglutide and tirzepatide are lifelong drugs.

Nevertheless, Garg is making very conservative recommendations and has repeatedly advised that patients try to taper off and discontinue their GLP-1 after reaching their weight loss goal. “We don’t know the long-term effects of these drugs. Nobody has done studies in type 1.”

Patients, of course, may have different ideas. More than one has told him flatly, “Dr. Garg, you’re never taking me off of this drug.”

A recent survey by Thrivable, a diabetes market research firm, demonstrated that people with type 1 diabetes who use GLP-1 drugs are far more likely to think positively about the future of diabetes treatment: 41.2 percent of GLP-1 users reported feeling optimistic, compared with a mere 5.6 percent of nonusers. The result suggests that new drugs are so effective that some people with type 1 diabetes will completely change their outlook on life with this chronic condition. “This medication changed everything for me,” said one respondent.

Using GLP-1s in People Without Excess Weight

What about the two-thirds of people with type 1 diabetes who do not have obesity?

Health experts have repeatedly warned that people who do not have a demonstrated medical need to use weight loss drugs should not use them. The use of GLP-1s in lean patients has not been studied, and there are some indications that it may pose special risks, including excessive muscle loss.

Lean adults with type 1 diabetes, however, arguably have multiple special reasons to take GLP-1 drugs:

Enhanced blood sugar control. GLP-1s could meaningfully improve glycemic outcomes. 
Beta cell protection. Last fall, a very small trial suggested that a small dose of semaglutide could dramatically reduce the need for insulin in new type 1 diabetes patients. The drug may somehow slow the progression of type 1 diabetes after diagnosis.
GLP-1s may uniquely benefit people with type 1 diabetes by correcting alpha cell dysfunction, a secondary feature of the condition that leads the liver to release excessive amounts of glucose into the bloodstream.
Cardiovascular protection. Semaglutide was recently approved by the FDA for heart attack and stroke prevention. Both of these severe outcomes are more common in people with type 1 diabetes.
Kidney protection. Though the FDA hasn’t yet endorsed GLP-1s for the prevention of kidney disease, the early evidence is extremely encouraging. Kidney disease is also extremely common in people with type 1 diabetes.

For now, Garg does not recommend GLP-1s to patients who are not overweight. The risks are far too unknown. But some of his more adventurous and determined patients have convinced him to let them try: 

“I have a few patients who are lean-bodied who are on these drugs. Do I want them to use them? No. But it keeps their blood sugar profile so flat, even I love it. Their A1C is down into the 6s. But at the back of my mind, I always have a hesitation that these individuals might go into ketosis.”

Garg hopes that the long-rumored development of a continuous ketone monitor — Abbott, the maker of the FreeStyle Libre continuous glucose monitor, has one in the works — could help lean patients using a GLP-1 more effectively guard against DKA. “That will change the way we use these drugs.”

“A handful of these people are using [GLP-1s], and we are seeing amazing results. There is no doubt in my mind that these drugs are going to have their use, even in normal-BMI people, for the overall glycemic effect.”

Critical Trials May Never Take Place

Garg’s experience offers valuable insights into the risks and benefits of GLP-1s for people with type 1 diabetes, but to really understand these drugs’ impact, there is a need for massive, long, rigorous randomized controlled clinical trials. The same trials will also be essential to convince insurers that they should pay GLP-1s for many people with type 1. Unfortunately, those experiments will not take place anytime soon — and may never.

Such trials can cost hundreds of millions of dollars to run. And thus far, the manufacturers of semaglutide and tirzepatide, Novo Nordisk and Eli Lilly, “have not indicated any desire” to organize major trials for type 1 treatment, according to Garg.

There are fewer than 10 million people with type 1 diabetes worldwide, hardly anything compared with the 500 million with type 2 diabetes and 2 billion who are overweight or have obesity. Contrasted with the wider potential market for Ozempic/Wegovy and Mounjaro/Zepbound, the type 1 diabetes population is nearly immaterial.

JDRF and other diabetes nonprofits could help advance the science by funding academic research studies. But ultimately it is only big pharma that has the financial heft to pay for the trials that the FDA wants to see.

The FDA, however, could force pharmaceutical companies to act. If the off-label use of GLP-1s for type 1 diabetes becomes so prevalent as to be impossible to ignore, the FDA “might mandate the companies to go and do these studies,” says Garg. But that day, if it ever comes, is likely many years away.

“I don’t know what the future will be, but I can tell you, these drugs are here to stay,” says Garg.

Takeaways

The blockbuster GLP-1 medications semaglutide and tirzepatide have incredible potential to help people with type 1 diabetes, offering weight loss, blood sugar reductions, and potentially long-term heart and kidney protection. Eventually, GLP-1s may even become important for the treatment of almost everyone with type 1 diabetes — even those who do not lose weight.

However, there is still much we don’t know about the use of GLP-1s to treat type 1 diabetes, and it may be many years before rigorous trials lead to official guidelines for clinicians. Patients and doctors alike should be extremely careful with this powerful class of medications, because these drugs pose risks that are unique to people with type 1 diabetes.

 

Editorial Sources & Fact-Checking