This content originally appeared on Everyday Health. Republished with permission.
By Ross Wollen
Medically Reviewed by Elise M. Brett, MD
New blockbuster GLP-1 drugs such as Ozempic and Mounjaro are perhaps the most effective drugs ever developed for type 2 diabetes and obesity. They could also have a transformative effect in the treatment of type 1 diabetes, too, but there are risks.
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 in Aurora, 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 and GIP agonist.[1][2] They show these blockbuster drugs can have exceptional benefits, including massive weight loss and significant blood sugar reductions.
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 also need to lose weight.
Eventually, 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 — [reducing the risk of] cardiovascular disease and kidney disease — and because glycemia [blood sugar control] is significantly improved.”
Type 1 Diabetes, Overweight, and Obesity
The classic stereotypical patient with type 1 diabetes 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.[3]
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.[4]
In short, people with type 1 diabetes need effective obesity treatment just as badly as everyone else does.
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.
Tirzepatide produced the most startling results. Garg’s 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, at 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 milligrams per deciliter (mg/dL).
- More time in range: Participants spent an additional 15 percent of their day within the target glucose range.
- Fewer glucose excursions: 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 strong and comprehensive improvements, including weight loss, better A1C, and increased time-in-range. The results were not quite as impressive as tirzepatide, though, particularly when it comes to weight loss: Semaglutide users lost an average of 16 pounds.
But GLP-1s Carry Serious Risks for People With Type 1 Diabetes
Despite the strong 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 infamous 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.
The risks, however, are sharply elevated for people with type 1 diabetes, because dehydrating illnesses like vomiting and diarrhea can lead rapidly to DKA, which is ultimately caused by a critical lack of insulin.[5] 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.
People with type 1 diabetes need to be especially cautious with GLP-1 medications because of DKA. The condition is fatal without emergency treatment.
GLP-1s and Hypoglycemia
On the other hand, GLP-1s can also increase the risk of severe low blood sugar because they radically impact insulin requirements. Most people with diabetes who take an injection of a GLP-1 drug will experience greater insulin sensitivity. GLP-1s themselves do not often cause hypoglycemia, 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 insulin dosing reductions as 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. In the real world, clinicians can’t easily provide that level of guidance.
Garg is “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 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 creative, unapproved 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, as explained by Everyday Health’s network site Diabetes Daily, 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.
The providers really don’t know how to use these drugs properly. All of the guidelines need to be written.
— Satish Garg, MD
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, Garg says. At the Barbara Davis Center, very few of the study participants who had been prescribed tirzepatide ever progressed to the higher available doses. And people with less weight to lose have even less need of large doses.
The need for smaller doses is most critical when children use 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, per Diabetes Daily, 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 it should be prescribed. Tirzepatide is not approved for people under 18.)[6]
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, 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.[7]
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.”
Questions to Ask Your Doctor
- Am I a good candidate for a GLP-1 drug?
- Do you think that these drugs would be safe for me?
- Would weight loss help ease my diabetes management?
- Has insulin made me gain weight?
- Do I have a high long-term risk of cardiovascular disease?
- How can we collaborate if I need to change my insulin dosing?
- When should I call your office, or visit the ER, in case of severe side effects?
- Is my prescription for emergency glucagon rescue medication current?
- Are you concerned about the long-term effects of GLP-1 drugs in people with type 1 diabetes?
- Are there any safer or less expensive alternatives to GLP-1s for weight loss and glucose-lowering?
- How can I find out whether my insurance plan covers these treatments?
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, many patients with type 1 have used a GLP-1 medication and lost weight. Of the hundreds 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.”
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.
— Satish Garg, MD
According to Diabetes Daily, 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 non-users. 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 anti-obesity 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. One very small trial has 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.[8][9]
- Cardiovascular protection. Wegovy was recently approved by the FDA for heart attack and stroke prevention in adults with established cardiovascular disease and either obesity or overweight. 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, Diabetes Daily notes 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 persuaded 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 sixes. But at the back of my mind, I always have a hesitation that these individuals might go into [DKA].”
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.”[10]
“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.”
Will Insurance Cover Ozempic for Type 1 Diabetes?
At the moment, it is unlikely that insurers will cover Ozempic and other GLP-1s specifically for the treatment of type 1 diabetes. Insurance companies tend to adhere to FDA guidelines, and no drugs in the family have been approved for use in the condition.
However, some people with type 1 diabetes may be eligible for coverage if they meet other health criteria. Wegovy is now FDA-indicated for cardiovascular risk reduction; insurers may cover the cost for adults who are overweight and have a higher risk of heart attack or stroke. Zepbound is indicated for overweight adults who have at least one weight-related health condition, including hypertension, high cholesterol, or sleep apnea.
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 the impact of these drugs, there is a need for massive, long, and rigorous randomized controlled trials. The same trials will also be essential to convince insurers that they should cover GLP-1s for many people with type 1.
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 two billion who are overweight or have obesity.[11][12][13] Contrasted with the wider potential market for Ozempic-Wegovy and Mounjaro-Zepbound, the type 1 diabetes population is nearly immaterial.
The type 1 diabetes research and advocacy organization JDRF and other diabetes nonprofits could help advance the science by funding academic research studies. Currently, however, only pharmaceutical companies have the financial heft to pay for the trials the FDA wants to see.
There is a chance the FDA 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.
The Takeaway
The blockbuster GLP-1 medications semaglutide and tirzepatide have incredible potential to help people with type 1 diabetes and overweight or obesity, offering weight loss, blood sugar reductions, and possibly long-term heart and kidney protection. Eventually, GLP-1s may become important for the treatment of almost everyone with type 1 diabetes — even those who do not need to 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.
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