This content material initially appeared on On a regular basis Well being. Republished with permission.
By Ross Wollen
Medically Reviewed by Elise M. Brett, MD
New blockbuster GLP-1 medicine corresponding to Ozempic and Mounjaro are maybe the simplest medicine ever developed for sort 2 diabetes and weight problems. They might even have a transformative impact within the remedy of sort 1 diabetes, too, however there are dangers.
Satish Garg, MD, has a daring prediction: “I’ve little question in my thoughts: Going ahead, this class of medicine goes for use by the overwhelming majority of individuals with sort 1 diabetes.”
Dr. Garg, a professor on the College of Colorado’s Barbara Davis Heart for Diabetes in Aurora, has authored two current research on the real-world use of GLP-1s to deal with sort 1 diabetes in people who find themselves additionally chubby or have weight problems: one on semaglutide (Ozempic, Wegovy) and one on tirzepatide (Mounjaro, Zepbound), which is technically a GLP-1 and GIP agonist.[1][2] They present these blockbuster medicine can have distinctive advantages, together with large weight reduction and important blood sugar reductions.
GLP-1 medicine will not be presently permitted by the U.S. Meals and Drug Administration (FDA) for the remedy of sort 1 diabetes — and so they could by no means be. However a rising variety of clinicians are prescribing them off-label, principally to folks with sort 1 who additionally have to shed pounds.
Ultimately, Garg thinks that nearly everybody with sort 1 diabetes shall be utilizing a GLP-1, even people who find themselves not chubby: “There are advantages above and past weight reduction, even in people with regular BMI [body mass index].”
“Smaller doses of those medicine shall be used routinely in folks with diabetes, not due to weight reduction, however due to the long-term advantages they could give — [reducing the risk of] heart problems and kidney illness — and since glycemia [blood sugar control] is considerably improved.”
Sort 1 Diabetes, Chubby, and Weight problems
The traditional stereotypical affected person with sort 1 diabetes is a baby who’s skinny and even emaciated. Acute hyperglycemia, the signature function of undiagnosed or uncontrolled diabetes, prevents the physique from harvesting power from meals; ultimately, the physique will begin burning physique fats and muscle for gasoline, resulting in unexplained weight reduction, amongst different signs.
Fortunately, that stereotype is now largely out of date, a minimum of within the developed world. Trendy insulin and glucose measurement expertise enable folks with sort 1 diabetes to dwell longer and more healthy lives. For higher or worse, additionally it is now far simpler to eat a regular food regimen, which signifies that folks with sort 1 have more and more begun to resemble their nondiabetic friends. One draw back to the shift is that extreme weight acquire is now nearly as prevalent within the sort 1 diabetes inhabitants as it’s within the normal inhabitants.[3]
The well being modifications related to chubby and weight problems can have unfavourable penalties for each short-term glucose administration and long-term well being. “Folks with sort 1 diabetes have the identical troubles as folks with sort 2,” says Garg, together with “weight acquire, insulin resistance, heart problems, and kidney illness.” In some instances, sufferers will develop double diabetes.[4]
In brief, folks with sort 1 diabetes want efficient weight problems remedy simply as badly as everybody else does.
Semaglutide, Tirzepatide, and Sort 1 Diabetes: The Knowledge
Garg’s current research evaluated the real-world use of GLP-1s prescribed to folks with sort 1 diabetes on the Barbara Davis Heart. For the time being, the usage of such medicine is nearly solely restricted to folks with a transparent medical have to shed pounds.
Tirzepatide produced essentially the most startling outcomes. Garg’s evaluation evaluated contributors with a median age of 40 and a median diabetes length of 24 years. Initially of the research, their common weight was 229 kilos. Most had been white and feminine.
Tirzepatide appeared to set off main metabolic enhancements throughout the board:
- Extraordinary weight reduction: After one 12 months, the common participant had misplaced 18.5 % of their physique weight, at 46.5 kilos. Among the sufferers misplaced as a lot as 200 kilos.
- A1C enchancment: The typical A1C dropped 0.67 proportion factors. Common blood sugar ranges dropped by 23.5 milligrams per deciliter (mg/dL).
- Extra time in vary: Individuals spent an extra 15 % of their day inside the goal glucose vary.
- Fewer glucose excursions: The amplitude of blood sugar swings declined considerably.
- Decrease insulin doses: Volunteers required far much less insulin, a median of 24.7 fewer items per day. Basal doses declined by about 10 items, bolus insulin by about 15 items.
“The advantages are unbelievable,” says Garg. “It actually flattens all of the glucose excursions.” And the burden loss was past his expectations.
Garg’s earlier trial of semaglutide additionally recognized robust and complete enhancements, together with weight reduction, higher A1C, and elevated time-in-range. The outcomes weren’t fairly as spectacular as tirzepatide, although, significantly in the case of weight reduction: Semaglutide customers misplaced a median of 16 kilos.
However GLP-1s Carry Severe Dangers for Folks With Sort 1 Diabetes
Regardless of the robust outcomes, there’s a purpose why specialists are very cautious about recommending the usage of semaglutide and tirzepatide for folks with sort 1 diabetes. These highly effective medicine carry very actual dangers for folks with the situation. The medicine should be managed in a novel manner, utilizing a brand new technique that specialists haven’t fairly agreed on but.
There are two lethal obstacles that every one folks with sort 1 diabetes continually have to navigate round: The threats of extreme low blood sugar (hypoglycemia) and diabetic ketoacidosis (DKA). GLP-1 medicine are suspected to boost the danger of every.
GLP-1s and DKA
GLP-1s have rapidly grow to be notorious for his or her dangerous gastrointestinal unwanted side effects. At its highest dosage, for instance, semaglutide causes diarrhea in 32 % and vomiting in 25 % of customers. For most individuals, these unwanted side effects disappear as their our bodies grow to be accustomed to the medicine.
The dangers, nonetheless, are sharply elevated for folks with sort 1 diabetes, as a result of dehydrating diseases like vomiting and diarrhea can lead quickly to DKA, which is finally brought on by a vital lack of insulin.[5] When folks with sort 1 diabetes can’t eat or drink resulting from a abdomen ailment, they’ll inevitably use much less insulin, which solely makes DKA much more more likely to develop.
Folks with sort 1 diabetes should be particularly cautious with GLP-1 drugs due to DKA. The situation is deadly with out emergency remedy.
GLP-1s and Hypoglycemia
However, GLP-1s may enhance the danger of extreme low blood sugar as a result of they radically affect insulin necessities. Most individuals with diabetes who take an injection of a GLP-1 drug will expertise larger insulin sensitivity. GLP-1s themselves don’t usually trigger hypoglycemia, but when customers with sort 1 diabetes don’t quickly alter their insulin utilization, they’re vulnerable to utilizing an excessive amount of and plunging their blood sugar all the way down to unsafe ranges.
On the Barbara Davis Heart for Diabetes, Garg instructs his sufferers to scale back their insulin by 20 % once they begin a GLP-1 for the primary time. He and his colleagues continued to recommend insulin dosing reductions as contributors stepped as much as greater GLP-1 dosages.
No one within the research was hospitalized with extreme low or excessive blood sugar. However Garg has had some scary experiences together with his personal sufferers who overcompensated and commenced taking even much less insulin than he suggested “as a result of they had been afraid of getting hypoglycemia. And that leads to a excessive threat of DKA.”
Garg took the potential risks severely: “We intently monitored these sufferers.” All contributors wore a steady glucose monitor (CGM), permitting docs to remotely observe their blood sugar ranges. In the true world, clinicians can’t simply present that degree of steering.
Garg is “completely” fearful about the usage of GLP-1s in much less rigorously managed circumstances. “I’m undoubtedly fearful that these medicine are going for use left and proper in folks with sort 1 diabetes.”
Folks With Sort 1 Diabetes Want Smaller GLP-1 Doses
One of the simplest ways to handle these two dangers, Garg believes, is to take smaller doses of GLP-1 drugs within the first place. Smaller doses and extra gradual dose escalation schedules can soften the affect of unwanted side effects and insulin requirement modifications.
That’s simpler mentioned than executed. Ozempic, Mounjaro, and different injectable medicine on this household are manufactured and distributed in exact, discrete doses that weren’t designed for the extra delicate our bodies of individuals with sort 1 diabetes. However there are artistic, unapproved methods of injecting much less medicine than the producers supposed.
A starter dose of Ozempic, for instance, is 0.25 milligrams (mg) per week. However Garg thinks that’s far an excessive amount of for most individuals with sort 1: “We’d begin them on 0.1 mg after which steadily over three months construct them up 1 or 2 mg per week.” It’s attainable to attract up smaller doses of semaglutide by counting clicks on the supply pen, as defined by On a regular basis Well being’s community web site Diabetes Day by day, a way that neither the FDA nor the producer endorses.
Tirzepatide is available in a pen machine that doesn’t enable for customized dosing in the identical manner. For smaller tirzepatide doses, Garg will generally ask his sufferers to take a dose each 10 days quite than each 7. A few of his sufferers go additional and extract exact smaller doses of tirzepatide from the pen utilizing an insulin syringe — a way that Garg doesn’t suggest.
The suppliers actually don’t know easy methods to use these medicine correctly. The entire pointers should be written.
— Satish Garg, MD
Smaller doses aren’t essentially only for the preliminary months of remedy. Clinicians is perhaps sensible to maintain sufferers with sort 1 on smaller GLP-1 doses all through their remedy, Garg says. On the Barbara Davis Heart, only a few of the research contributors who had been prescribed tirzepatide ever progressed to the upper obtainable doses. And folks with much less weight to lose have even much less want of huge doses.
The necessity for smaller doses is most crucial when kids use these medicine. Garg insists that many docs and endocrinologists are already prescribing GLP-1s to kids who’re chubby and have sort 1 diabetes, regardless of an entire lack of research or official steering on the difficulty. Kids have smaller our bodies, in fact, however adolescence may also be a very difficult time for blood sugar administration. Hormonal modifications are likely to introduce dramatic shifts in insulin sensitivity, per Diabetes Day by day, making it much more vital to proactively handle threat. (Semaglutide is permitted for weight reduction in adolescents ages 12 and up, although there may be some controversy over how steadily it needs to be prescribed. Tirzepatide isn’t permitted for folks beneath 18.)[6]
New Tips Are Wanted
Garg states that the usage of GLP-1s to deal with sort 1 diabetes is already fairly frequent. However there’s no telling in the event that they’re being prescribed and used safely in the true world: “The suppliers actually don’t know easy methods to use these medicine correctly. The entire pointers should be written.”
In a current editorial, Garg and his colleagues shared their finest practices for the protected and efficient use of GLP-1s in folks with sort 1 diabetes. Listed here are among the most important takeaways for clinicians:
- Scale back insulin dose by 20 to 30 % when initiating GLP-1 remedy.
- Alter insulin doses when sufferers step as much as bigger GLP-1 doses.
- Titrate GLP-1 doses extra slowly than the producers suggest, stepping up each two or three months quite than month-to-month.
- Sufferers can “depend clicks” to make use of smaller doses of semaglutide.
- Sufferers can use tirzepatide much less steadily than each seven days.
- Make it possible for sufferers have glucagon rescue medicine at residence.
- Instruct sufferers to check ketone ranges frequently.[7]
Although these suggestions are primarily based on stable scientific expertise, Garg and his colleagues are nonetheless simply making educated guesses a few largely unstudied phenomenon. There have been loads of research on older, much less highly effective medicine within the GLP-1 class, corresponding to liraglutide, however semaglutide and tirzepatide symbolize new territory.
“The correct research should be executed to study one of the simplest ways to make use of these medicine, that are undoubtedly wanted in folks with sort 1 diabetes.”
Inquiries to Ask Your Physician
- Am I an excellent candidate for a GLP-1 drug?
- Do you assume that these medicine could be protected for me?
- Would weight reduction assist ease my diabetes administration?
- Has insulin made me acquire weight?
- Do I’ve a excessive long-term threat of heart problems?
- How can we collaborate if I want to vary my insulin dosing?
- When ought to I name your workplace, or go to the ER, in case of extreme unwanted side effects?
- Is my prescription for emergency glucagon rescue medicine present?
- Are you involved concerning the long-term results of GLP-1 medicine in folks with sort 1 diabetes?
- Are there any safer or cheaper alternate options to GLP-1s for weight reduction and glucose-lowering?
- How can I discover out whether or not my insurance coverage plan covers these remedies?
Do You Have to Take GLP-1s Endlessly?
It’s extensively believed that GLP-1s should be used indefinitely or the advantages will go away.
On the Barbara Davis Heart, many sufferers with sort 1 have used a GLP-1 medicine and misplaced weight. Of the a whole lot who’ve ceased to make use of the drug, solely three have been capable of hold the burden off. In all probability, semaglutide and tirzepatide are lifelong medicine.
However, Garg is making very conservative suggestions and has repeatedly suggested that sufferers attempt to taper off and discontinue their GLP-1 after reaching their weight reduction purpose. “We don’t know the long-term results of those medicine. No one has executed research in sort 1.”
Sufferers, in fact, could have completely different concepts. Multiple has advised him flatly, “Dr. Garg, you’re by no means taking me off of this drug.”
I’ve little question in my thoughts: Going ahead, this class of medicine goes for use by the overwhelming majority of individuals with sort 1 diabetes.
— Satish Garg, MD
Based on Diabetes Day by day, a current survey by Thrivable, a diabetes market analysis agency, demonstrated that individuals with sort 1 diabetes who use GLP-1 medicine are much more more likely to assume positively about the way forward for diabetes remedy: 41.2 % of GLP-1 customers reported feeling optimistic, in contrast with a mere 5.6 % of non-users. The consequence means that new medicine are so efficient that some folks with sort 1 diabetes will utterly change their outlook on life with this power situation. “This medicine modified every little thing for me,” mentioned one respondent.
Utilizing GLP-1s in Folks With out Extra Weight
What concerning the two-thirds of individuals with sort 1 diabetes who shouldn’t have weight problems?
Well being specialists have repeatedly warned that individuals who shouldn’t have a demonstrated medical want to make use of anti-obesity medicine mustn’t use them. Using GLP-1s in lean sufferers has not been studied, and there are some indications that it might pose particular dangers, together with extreme muscle loss.
Lean adults with sort 1 diabetes, nonetheless, arguably have a number of particular causes to take GLP-1 medicine:
- Enhanced blood sugar management. GLP-1s might meaningfully enhance glycemic outcomes.
- Beta cell safety. One very small trial has prompt {that a} small dose of semaglutide might dramatically cut back the necessity for insulin in new sort 1 diabetes sufferers. The drug could someway gradual the development of sort 1 diabetes after prognosis.
- GLP-1s could uniquely profit folks with sort 1 diabetes by correcting alpha cell dysfunction, a secondary function of the situation that leads the liver to launch extreme quantities of glucose into the bloodstream.[8][9]
- Cardiovascular safety. Wegovy was just lately permitted by the FDA for coronary heart assault and stroke prevention in adults with established heart problems and both weight problems or chubby. Each of those extreme outcomes are extra frequent in folks with sort 1 diabetes.
- Kidney safety. Although the FDA hasn’t but endorsed GLP-1s for the prevention of kidney illness, Diabetes Day by day notes the early proof is extraordinarily encouraging. Kidney illness can be extraordinarily frequent in folks with sort 1 diabetes.
For now, Garg doesn’t suggest GLP-1s to sufferers who will not be chubby. The dangers are far too unknown. However a few of his extra adventurous and decided sufferers have persuaded him to allow them to strive:
“I’ve just a few sufferers who’re lean-bodied who’re on these medicine. Do I would like them to make use of them? No. However it retains their blood sugar profile so flat, even I like it. Their A1C is down into the sixes. However in the back of my thoughts, I all the time have a hesitation that these people may go into [DKA].”
Garg hopes that the long-rumored growth of a steady ketone monitor — Abbott, the maker of the FreeStyle Libre steady glucose monitor, has one within the works — might assist lean sufferers utilizing a GLP-1 extra successfully guard in opposition to DKA. “That can change the best way we use these medicine.”[10]
“A handful of those individuals are utilizing [GLP-1s], and we’re seeing superb outcomes. There isn’t any doubt in my thoughts that these medicine are going to have their use, even in normal-BMI folks, for the general glycemic impact.”
Will Insurance coverage Cowl Ozempic for Sort 1 Diabetes?
For the time being, it’s unlikely that insurers will cowl Ozempic and different GLP-1s particularly for the remedy of sort 1 diabetes. Insurance coverage corporations have a tendency to stick to FDA pointers, and no medicine within the household have been permitted to be used within the situation.
Nonetheless, some folks with sort 1 diabetes could also be eligible for protection in the event that they meet different well being standards. Wegovy is now FDA-indicated for cardiovascular threat discount; insurers could cowl the price for adults who’re chubby and have the next threat of coronary heart assault or stroke. Zepbound is indicated for chubby adults who’ve a minimum of one weight-related well being situation, together with hypertension, excessive ldl cholesterol, or sleep apnea.
Essential Trials Might By no means Take Place
Garg’s expertise affords helpful insights into the dangers and advantages of GLP-1s for folks with sort 1 diabetes, however to essentially perceive the affect of those medicine, there’s a want for large, lengthy, and rigorous randomized managed trials. The identical trials may also be important to persuade insurers that they need to cowl GLP-1s for many individuals with sort 1.
Such trials can value a whole lot of thousands and thousands of {dollars} to run. And so far, the producers of semaglutide and tirzepatide, Novo Nordisk and Eli Lilly, “haven’t indicated any need” to prepare main trials for sort 1 remedy, in accordance with Garg.
There are fewer than 10 million folks with sort 1 diabetes worldwide, hardly something in contrast with the 500 million with sort 2 diabetes and two billion who’re chubby or have weight problems.[11][12][13] Contrasted with the broader potential marketplace for Ozempic-Wegovy and Mounjaro-Zepbound, the kind 1 diabetes inhabitants is almost immaterial.
The sort 1 diabetes analysis and advocacy group JDRF and different diabetes nonprofits might assist advance the science by funding educational analysis research. At present, nonetheless, solely pharmaceutical corporations have the monetary heft to pay for the trials the FDA needs to see.
There’s a probability the FDA might power pharmaceutical corporations to behave. If the off-label use of GLP-1s for sort 1 diabetes turns into so prevalent as to be not possible to disregard, the FDA “may mandate the businesses to go and do these research,” says Garg. However that day, if it ever comes, is probably going a few years away.
“I don’t know what the long run shall be, however I can inform you, these medicine are right here to remain,” says Garg.
The Takeaway
The blockbuster GLP-1 drugs semaglutide and tirzepatide have unbelievable potential to assist folks with sort 1 diabetes and chubby or weight problems, providing weight reduction, blood sugar reductions, and presumably long-term coronary heart and kidney safety. Ultimately, GLP-1s could grow to be vital for the remedy of virtually everybody with sort 1 diabetes — even those that don’t have to shed pounds.
Nonetheless, there may be nonetheless a lot we don’t learn about the usage of GLP-1s to deal with sort 1 diabetes, and it might be a few years earlier than rigorous trials result in official pointers for clinicians. Sufferers and docs alike needs to be extraordinarily cautious with this highly effective class of medicines, as a result of these medicine pose dangers which might be distinctive to folks with sort 1 diabetes.
