The most toxic thing we tell people with type 1 diabetes:
“You can do whatever you want! Just take the right amount of insulin for it.”
Many people with type 1 diabetes take this to heart not realizing that they too can experience insulin resistance and other hormonal imbalances our type 2 friends typically deal with. We soon realize that it’s never as simple as just “taking the insulin.” Diabetes management then becomes more difficult and leads to some serious burnout. We wonder “what the heck am I doing wrong? Why isn’t the insulin just working?”
I was diagnosed with type 1 diabetes at the itty bitty age of 5 years old and have never known a life without it. As I’ve gotten older, I’ve noticed my body changing, and the ease of my diabetes management along with it. Type 2 diabetes runs on my father’s side of the family (dad, uncle, aunt, grandma, and great grandpa). I’m pretty convinced that I have been gifted those very genes. The autoimmune complete beta cell destruction of type 1 diabetes with the insulin resistance of someone with type 2 diabetes is my magical unicorn of double diabetes.
The extreme stress and the circadian destruction that is night shift when I started my career as an RN really set things off. My insulin needs increased significantly, I gained thirty pounds very quickly, and was really struggling to get my insulin to do ANYTHING.
Enter off-label metformin. My doctor and I decided to try it in order to help bring me back to where I was previous to my night-shift-new-grad-nurse-roller-coaster-experience.
And it worked. Within a few months, my insulin needs were cut in half from where they were and my insulin worked much more effectively. Don’t get me wrong, I’ll never be where I was 25 years ago. But it’s improved.
Wondering if you and your type 1 diabetes could benefit from metformin? Let’s talk first about metabolic syndrome and it’s prevalence in the T1D population.
What is metabolic syndrome?
Metabolic syndrome is a cluster of conditions that occur together, increasing a person’s risk of heart disease, stroke, and type 2 diabetes. These conditions include increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels (“Metabolic syndrome — Symptoms and causes”, 2021).
Risk of metabolic syndrome increases with age, genetics, gestational diabetes, and a family history of type 2 diabetes. Risk also increases if you’ve ever been diagnosed with nonalcoholic fatty liver disease, polycystic ovary syndrome, or sleep apnea (“Metabolic syndrome — Symptoms and causes”, 2021).
Metabolic syndrome and type 1 diabetes
Metabolic syndrome with type 1 diabetes can present an especially challenging problem. People with type 1 diabetes do not produce any insulin and when paired with metabolic syndrome, they are insulin resistant. This means that injected insulin doses will need to be increased significantly, which can put a person more at risk for hypoglycemia and more variable blood sugars.
Recent research has found overall prevalence of metabolic syndrome in people with type 1 diabetes was 38% in men and 40% in women. Prevalence increased as glycemic control and creatinine clearance decreased from target range (Ghosh et al., 2010, p. 38).
Not only does metabolic syndrome make day to day management more difficult (like does this insulin even works?!?!), but it is associated with a higher incidence of diabetes-related complications (Ghosh et al., 2010, p. 41).
With metabolic syndrome’s significant prevalence in people with type 1 diabetes, more research is needed using “type 2 medications” in type 1 diabetes. Insulin therapy just isn’t enough.
A great off-label place to start though is with my absolute fave…
Metformin
I love it. It’s cheap, it’s effective, and safe for long term use.
How metformin works
Did I just read through a history of metformin for you? You bet I did. Check this out:
“[Metformin’s] history is linked to Galega officinalis (also known as goat’s rue), a traditional herbal medicine in Europe, found to be rich in guanidine, which, in 1918, was shown to lower blood glucose.” (Bailey, 2017, p. 1566)
So all of the pro herbal medicine people can rest assured that metformin is derived from a botanical (as most drugs are). French physician Jean Sterne first reported the use of metformin to treat diabetes in 1957.” (Bailey, 2017, p. 1566)
It did not gain popularity, however, until the late 90’s, but it is now the most prescribed glucose-lowering medicine worldwide.(Bailey, 2017, p. 1566). And for good reason. Metformin works a few different ways to lower blood sugar levels in people with diabetes:
It sensitizes the body’s response to insulin
It decreases the amount of sugar the intestines and stomach absorb
It tells your liver to quit dumping sugar at inappropriate times (Nasri and Rafieian-Kopaei, 2014, p. 1)
Cool, right? Now, I’m sure you’ve heard lots of rumors and anecdotes about metformin, so let’s talk a little bit about those.
Side Effects
Remember how metformin acts on your intestines and stomach? This is partially why most people tend to experience the dreaded metformin poops (AKA some serious diarrhea and gastrointestinal distress).
“But Rachel. Why on earth would metformin be your favorite drug if it gives people the uncontrollable poops?”
Enter extended release metformin. This formulation was developed a bit later on and it is released in the body over 24 hours unlike it’s immediate release counterpart. This minimizes (or even gets rid of) gastrointestinal side effects and allows the person with diabetes to take it on a more compressed schedule.
Some other ways you can avoid the metformin poops is by
Asking your doctor if you can split the dose up through out the day
Taking it with a good quality, enteric coated probiotic
Taking it with meals
Some other things you should know about metformin:
It is important to have your kidney labs monitored while taking this medication as it is processed in the kidneys. If someone has decreased kidney function, the dose will need to be adjusted or stopped.
(THIS DOES NOT MEAN METFORMIN CAUSES KIDNEY DAMAGE. In fact, it’s arguable that it helps prevent kidney damage by keeping blood sugars in range.)
Long term use of metformin is safe but sometimes results in low B12 levels. Your doctor will monitor these as well and let you know if supplementation is needed.
How to get a prescription
The best part about metformin the cost. It’s inexpensive and covered by most insurance plans in the United States. After processing tons of prescriptions for it as an endocrinology RN, I do have some tips for you:
Ask your doctor for the extended release version right off the bat (honestly, there’s no time for those side effects, so save yourself the trouble)
Make sure your doctor writes for the generic metformin
Majority of the time, if your insurance is denying the prescription, it’s because your provider wrote for the name brand OR your plan won’t cover the 1,000mg tablets (I have no clue why this happens so often but it’s very common)
The prescription should look like this:
Metformin Extended Release ER (generic for Glucophage XR) 500mg tablets Take 2 tablets twice a day with meals
I personally buy my extended release metformin out of pocket without my insurance at Mark Cuban’s Cost Plus Drug Company. A 90 day supply costs me about $20 (OptumRx was trying to charge me $32 because they’re corrupt idiots).
If you don’t mind doing some shopping around, pharmacies all have different costs on their medications. Don’t be afraid to look for better options.
Metformin use in type 1 diabetes
We know that type 2 diabetes benefits greatly from metformin. But what about type 1 diabetes or double diabetes? If someone with type 1 diabetes is experiencing significant insulin resistance, adding more insulin is not necessarily going to help and may put the person at further risk for hypoglycemia and potentially increase blood pressure and LDL-cholesterol levels. (Livingstone et al., 2017, p. 1595). This person is going to need help from an insulin sensitizer like metformin.
A small retrospective study looked at 29 adults with type 1 diabetes. It found that “metformin decreased glucose concentrations, reduced metabolic syndrome, as well as insulin dose requirement more than insulin therapy alone, 1 year after treatment. These results were independent of blood lipid improvement or weight loss, although on average weight remained decreased with metformin-insulin therapy, whereas the average weight increased with insulin therapy alone.” (Beysel et al., 2018, p. 1)
Adolescents are at particular risk for metabolic syndrome during puberty due to shifting hormones and changes in the body. A review of 10 articles found that the majority of studies demonstrated that metformin improved insulin resistance when used in adolescent type 1 diabetics (Sikorskaya et al., 2021, p. 5). Four studies even showed that metformin REPAIRED vascular damage in the participants. So not only can it be used as a preventative measure but also a treatment protocol (Sikorskaya et al., 2021, p. 5).
A systematic review and meta analysis (the creme de la creme of research) was done in 2010. Researchers found a significant reduction in insulin dose requirements (6.6 U/day, p < 0.001) in type 1 participants using metformin. The evidence was mixed and unclear as to whether metformin could help improve Hgb A1c (Livingstone et al., 2017, p. 1599).
I do think it’s important to note that even though there was not enough evidence to support improvement in glycemic control, the benefits of reducing overall insulin requirements are significant:
Less risk for hypoglycemia and better management of fear of hypoglycemia and diabetes self management overall
Reduce weight fluctuations which can decrease risk for or improve metabolic syndrome
Decrease the burden of insulin cost and potential for rationing
More research and more options are needed
Just as people with type 2 diabetes have various interventions for their diabetes, people with type 1 diabetes need the same. Especially when faced with decreased insulin sensitivity and other symptoms of metabolic syndrome. While metformin can be a cost-effective option, more research should be done on type 1 diabetes and use of GLP-1/GIP agonists and other insulin sensitizers. Drug companies should consider submitting for FDA approval in order to improve accessibility.
References
American Diabetes Association. (n.d.). Metabolic Syndrome in Type 1 Diabetes | Diabetes Care. Retrieved April 16, 2023, from https://diabetesjournals.org/care/article/28/8/2019/23775/Metabolic-Syndrome-in-Type-1-DiabetesAssociation Bailey, C. J. (2017). Metformin: Historical overview. Diabetologia, 60(9), 1566–1576. https://doi.org/10.1007/s00125-017-4318-z Beysel, S., Unsal, I. O., Kizilgul, M., Caliskan, M., Ucan, B., & Cakal, E. (2018). The effects of metformin in type 1 diabetes mellitus. BMC Endocrine Disorders, 18, 1. https://doi.org/10.1186/s12902-017-0228-9 Ford, E. S., Giles, W. H., & Dietz, W. H. (2002). Prevalence of the metabolic syndrome among US adults: Findings from the third National Health and Nutrition Examination Survey. JAMA, 287(3), 356–359. https://doi.org/10.1001/jama.287.3.356 Ghosh, S., Collier, A., Hair, M., Malik, I., & Elhadd, T. (2010). Metabolic syndrome in type 1 diabetes. International Journal of Diabetes Mellitus, 2(1), 38–42. https://doi.org/10.1016/j.ijdm.2009.10.005 Lee, A. S., Twigg, S. M., & Flack, J. R. (2021). Metabolic syndrome in type 1 diabetes and its association with diabetes complications. Diabetic Medicine, 38(2), e14376. https://doi.org/10.1111/dme.14376 Livingstone, R., Boyle, J. G., & Petrie, J. R. (2017). A new perspective on metformin therapy in type 1 diabetes. Diabetologia, 60(9), 1594–1600. https://doi.org/10.1007/s00125-017-4364-6 Metabolic syndrome — Symptoms and causes. (2021, May 6). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/metabolic-syndrome/symptoms-causes/syc-20351916 Nasri, H., & Rafieian-Kopaei, M. (2014). Metformin: Current knowledge. Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences, 19(7), 658–664. Sikorskaya, K., Zarzecka, I., Ejikeme, U., & Russell, J. (2021). The use of metformin as an add-on therapy to insulin in the treatment of poorly controlled type 1 diabetes mellitus in adolescents. Metabolism Open, 9, 100080. https://doi.org/10.1016/j.metop.2021.100080