Insulin therapy is a lifesaving necessity for people with
type 1 diabetes, and it’s essentially the only medication approved for managing the condition. But a variety of additional blood-sugar-lowering medications are approved for
type 2 diabetes, and some doctors are eager to use these drugs to help improve the results for people with type 1 diabetes.
When a clinician prescribes a medication for a purpose for which it’s not indicated by the U.S. Food and Drug Administration (FDA), it’s referred to as off-label treatment.
Doctors may recommend off-label treatments to people with type 1 diabetes to help them reach their
A1C goals, lower their insulin requirements, or lose weight.
Though the off-label use of type 2 diabetes drugs may have potential benefits for people with type 1 diabetes, the practice also comes with enhanced risks of
hypoglycemia and
diabetic ketoacidosis (DKA).
None of these drugs should ever be used without very close clinician supervision.
GLP-1 Receptor Agonists
Though the drugs are not approved for the treatment of type 1 diabetes, doctors are increasingly
prescribing GLP-1 drugs off-label to help with both weight and blood sugar management.
“More and more clinicians are using GLP-1s off-label in people with type 1 diabetes, particularly in those who also have obesity or high insulin requirements,” says Mihail Zilbermint, MD, an associate professor of medicine at Johns Hopkins University School of Medicine and the chief of the division of endocrinology, diabetes, and metabolism at Suburban Hospital in Maryland.
The Benefits
Dr. Zilbermint says that GLP-1s can help lead to fairly meaningful weight loss, improve blood sugar modestly, and reduce an individual’s daily insulin needs:
- Weight Loss Improved insulin and blood sugar management techniques have allowed people with type 1 diabetes to live increasingly normal lifestyles, so the incidence of obesity has risen within the community. GLP-1 drugs help people with type 1 diabetes lose weight, which can make diabetes management easier.
- Decreased Insulin Needs GLP-1s help the body become more sensitive to insulin, which can lead to significantly lower insulin doses.
GLP-1 drugs also have a wide variety of positive long-term health effects, from lower blood pressure and cholesterol to improved kidney health, which may help guard against some of the most prominent and dangerous complications of type 1 diabetes.
The Risks
Gastrointestinal side effects like nausea, vomiting, and diarrhea are common among people with type 1 diabetes who take GLP-1 medications.
Another challenge with GLP-1 use in someone with type 1 diabetes is the potential risk of hypoglycemia, or low blood sugar. It’s the reason the FDA has been hesitant to approve GLP-1 use for people with type 1 diabetes, says Dace Trence, MD, the president of American Association of Clinical Endocrinology and a professor emeritus at the University of Washington in Seattle.
The risk may be especially elevated when you use GLP-1 drugs for the first time. If they supercharge your insulin sensitivity, and you don’t quickly adjust your doses to compensate, you could end up with a dangerously low blood sugar level. However, with the right adjustments and the close collaboration of your endocrinologist, your risk of hypoglycemia may not rise much at all.
GLP-1 drugs also have the potential to trigger the development of DKA. Preliminary research suggests that this side effect is not common, but DKA nevertheless remains a potential consequence of the dehydrating side effects like vomiting and diarrhea that GLP-1 drugs are known to cause.
Dr. Trence says that people with type 1 diabetes face similar
gastrointestinal side effects with GLP-1 use as people who use the drugs for type 2 diabetes or weight loss.
DKA, which is ultimately caused by a lack of insulin, is frequently triggered by dehydrating illnesses.
Because of these risks, doctors may choose to prescribe very small doses of GLP-1s to people with type 1 diabetes, especially if they do not have a lot of weight to lose.
Metformin
Metformin has been used for decades as a therapy for type 2 diabetes.
This pill helps decrease blood sugar by boosting insulin sensitivity and minimizing the liver’s production of glucose.
For people with type 1 diabetes, metformin may aid weight loss, lower blood sugar, and decrease how much insulin that people need to take daily.
“The main goal in type 1 diabetes management is to try and minimize the amount of insulin that might be required,” says Trence. She says that metformin can often serve as an easy add-on treatment because it’s relatively affordable and has been around for a long time.
The Benefits
Metformin may hold a number of possible benefits for people with type 1 diabetes:
- Decreased Daily Insulin Needs One systematic review and meta-analysis found that in adolescents with type 1 diabetes, metformin lowered total daily insulin needs by an average of 0.61 units per kg. In adults, it lowered total daily insulin needs by 0.44 units per kg.
- Lower Blood Sugar Levels Metformin may modestly reduce A1C in people with type 1 diabetes by an average of about 0.3 percentage points.
- Weight Loss Metformin may help lower body mass index in both adolescents and adults with type 1 diabetes.
However, it’s possible that these effects may be temporary.
Zilbermint says metformin may help reduce
insulin resistance, too, although evidence is mixed.
Some data also suggests that people with type 1 diabetes who take metformin may experience possible cardiovascular benefits.
The Risks
People with type 1 diabetes who take metformin may have an increased risk of experiencing low blood sugar.
However, Trence says that such incidences tend to be very mild. In addition to knowing how to recognize
symptoms of hypoglycemia, she recommends wearing a
continuous glucose monitor to keep track of blood sugar more easily.
It’s also possible to experience gastrointestinal issues with metformin.
In general, there’s a rare but possible risk of experiencing metformin-associated lactic acidosis. In this condition, the body’s normal process of metabolizing lactate and hydrogen changes in a way that can be life-threatening.
Zilbermint says that for people with type 1 diabetes who have kidney problems like
diabetic nephropathy, it’s critical to see whether their kidney function can support the planned dose of metformin because of this risk.
With that said, this caution doesn’t automatically restrict them from taking metformin entirely.
SGLT-2 Inhibitors
SGLT-2 inhibitors help control blood sugar by blocking a protein in the kidneys called SGLT-2 that’s responsible for reabsorbing glucose back into the bloodstream.
Simplistically, SGLT-2 inhibitors “just make you pee out sugar,” says Trence. “People with very high-dose needs of insulin are typically very insulin resistant. They have to use high doses to try and get their blood sugar under control. If you can drive down blood sugar, then you don't need as much insulin to control it.”
The Benefits
In individuals with type 1 diabetes, use of SGLT-2 inhibitors may help lower A1C, weight, and insulin needs.
- Improved Blood Sugar SGLT-2 inhibitors can improve A1C by 0.20 to 0.45 percentage points while also improving time in range.
- Weight Loss One study found that after one year, participants with type 1 diabetes who took an SGLT-2 inhibitor had an average weight loss of 4.4 percent. Some trials in overweight individuals with type 1 diabetes report up to a 13.3 percent reduction in body weight when taking the SGLT-2 inhibitor empagliflozin.
- Lower Insulin Doses SGLT-2 inhibitor use may help significantly lower basal insulin doses.
These drugs may also lower a person’s risk for
heart failure and
chronic kidney disease,
though more research is needed to understand their precise long-term benefits in people with type 1 diabetes.
The Risks
Most concerningly, SGLT-2 inhibitors can increase the risk of DKA.
Zilbermint says that this is because SGLT-2 inhibitors can lead to dangerous metabolic imbalances. And while DKA is usually accompanied by very high blood sugar levels, this isn’t always the case when it is precipitated by the use of SGLT-2 drugs.
The risk is even higher for people with diabetes who choose a low-carbohydrate diet.
“In the use of the SGLT-2s, the sugar doesn't need to be necessarily high,” says Trence. “It can actually be on the relatively high end of normal or midnormal. It can be a confusing picture.”
Because SGLT-2 inhibitors increase the amount of sugar in urine, they can also increase your risk for urinary tract infections and vaginal infections, says Trence. “If the person is very prone to such infections already, you don’t want to add an SGLT-2 to their medication regimen,” she says.
As with other glucose-lowering medications, there’s a risk of experiencing low blood sugar as well.
Discussing Your Options
It’s critical to discuss any off-label use of medications with your healthcare provider. “Talk with your endocrinologist to really understand the benefits and the risks that you’re undertaking,” says Trence.
“People with type 1 diabetes also need to understand that this is a process,” she says. “We need to go slow and make sure that you don't have any problems such as low blood sugar.”
