GLP 1 agonist with DM Type 1

[John Tang]

Does anybody have any experience using it like Ozempic with a patient who has DM Type 1 or DM Type 1 who is still producing a small amount of insulin?  Is this contraindicated?  I have started to use in DM Type  2 with good success but don’t know about this in Type 1.

[Kristelle Reyes]

Hello @cpaigepaigemd-com and @leonard-pastranagmail-com, would love to have your insights here. Thank you 🙂

[Madison Lepore]

Type 1 DM:

• Autoimmune disease that leads to destruction of insulin-producing pancreatic beta cells
• Believe to be have a strong link with HLA (DR & DQ) alleles
• Circulating pancreatic autoantibodies (islet cell cytoplasmic antibodies (ICA), antibodies to insulin (IAA), glutamic acid decarboxylase (GAD65), protein tyrosine phosphatase antibodies (IA-1) and zinc transporter8 (ZnT8)) indicate a risk of developing T1DM or already developed
• Potential cause for developing T1DM in patients at risk is a viral or environmental factor triggers autoimmune beta-cell destruction
• Occurs in 3 stages
• Requires Insulin Therapy

Type 2 DM:

• Metabolic Disorder
• Two primary leading causes:
  • Defective insulin secretion by pancreatic B-cells
    • Insulin secretion is reduced so the body’s ability to maintain physiological glucose levels is reduced
  • Inability of insulin-sensitive tissues to respond appropriately to insulin
    • Leads to high blood glucose levels
  • Modifiable risk factors:
    • Obesity
    • Low physical activity
    • Unhealthy diet
  • Non-modifiable risk factors:
    • Ethnicity
    • Family history
  • Does not necessarily require Insulin treatment

Insulins Job in the Body:

• Allows glucose to enter muscle and adipose cells
• Stimulates liver to store glucose as glycogen and synthesize fatty acids
• Stimulates uptake of amino acids
• Inhibits breakdown of fat in adipose tissue
• Stimulates uptake of potassium into cells

Signaling Pathway for Insulin secretion:

• Release is triggered by response to high glucose concentration and glucose internalized through GLUT2 transporter in the beta cell of the pancreas
• Glucose catabolism increases ATP/ADP ratio
• ATP-dependent potassium channels are closed therefore membrane depolarization and opening of calcium channels
• Calcium influx triggers insulin exocytosis
• P2x, P2Y, SERCA and RYR (additional calcium channels) that are involved in calcium mobilization and insulin secretion

Glucagon Like Peptide-1 Receptor Agonists  

• Stimulate insulin secretion after oral glucose via incretin effect
• When used to treat T2DM benefits are:
  • Delayed gastric emptying
  • Inhibiting production of glucagon from pancreatic alpha cells if blood sugar levels elevated
  • Decrease pancreatic beta-cell apoptosis
  • Promotes proliferation of beta-cells
  • Weight loss
  • Lowered HGB-A1C
• Other Benefits:
  • Blood pressure was decreased
  • Total cholesterol levels were decreased
  • Risk of a cardiovascular event is decreased
  • Increased glucose uptake in muscles
  • Decreased glucose production in the liver
  • Neuroprotective
  • Increased satiety

Management of T1DM:

• Current “approved” management of T1DM is inulin & pramlintide
• Insulin does not target alpha cell dysfunction
• When a GLP-1RA is used in T1DM it addresses the alpha cell dysfunction which results in suppression of glucagon secretion. Patients who have T1DM cannot suppress glucagon during meals which results in postprandial hyperglycemia
• Studies have been done using Exenatide and Liraglutide for patients with T1DM and the results were decreases in total daily insulin requirements, weight loss and improvements in glycemic control
• Studies have shown positive results using a GLP-1RA in the management of T1DM

In our practice we are currently using Semaglutide as our GLP-1RA instead of Liraglutide(which we were using previous to semaglutide with success) and we have been implementing this therapy with T1DM. So far, we have had positive results where patients have been able to decrease the amount their insulin dose.

 

References:

 

Harris, Kira B., and Cassie L. Boland. “Adjunctive Role of Glucagon-Like Peptide-1 Receptor Agonists in the Management of Type 1 Diabetes Mellitus.” Pharmacotherapy 36, no. 9 (September 2016): 1011–20. https://doi.org/10.1002/phar.1804.

 

Zhao, Xin, Minghe Wang, Zhitong Wen, Zhihong Lu, Lijuan Cui, Chao Fu, Huan Xue, Yunfeng Liu, and Yi Zhang. “GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects.” Frontiers in Endocrinology 12 (2021): 1040. https://doi.org/10.3389/fendo.2021.721135.

 

Lucier, Jessica, and Ruth S. Weinstock. “Diabetes Mellitus Type 1.” In StatPearls. Treasure Island (FL): StatPearls Publishing, 2021. http://www.ncbi.nlm.nih.gov/books/NBK507713/.

 

Galicia-Garcia, Unai, Asier Benito-Vicente, Shifa Jebari, Asier Larrea-Sebal, Haziq Siddiqi, Kepa B. Uribe, Helena Ostolaza, and César Martín. “Pathophysiology of Type 2 Diabetes Mellitus.” International Journal of Molecular Sciences 21, no. 17 (August 30, 2020): 6275. https://doi.org/10.3390/ijms21176275.

 

Hou, June Chunqiu, Dumaine Williams, Jérôme Vicogne, and Jeffrey E. Pessin. “The Glucose Transporter 2 Undergoes Plasma Membrane Endocytosis and Lysosomal Degradation in a Secretagogue-Dependent Manner.” Endocrinology 150, no. 9 (September 2009): 4056–64. https://doi.org/10.1210/en.2008-1685.

 

@rejuve06gmail-com

[Aaron Hartman]

Madison,

Thanks for that data filled response.

My clinical research company, Virginia Research Center, did some of the initial studies with GLP-1’s almost 10 years ago and we’ve been involved with research on them since as a primary prevention for acute coronary syndromes as well as weight loss. I’ve used it in my Type I patients with great success. I use it primarily to decrease their insulin usage (due to how bad long term insulin usage can be) and in a few who followed a strict diet, I was able to get them back to physiologic insulin dosages (for example one patient was on 50 Units daily and got him down to 10).

Aaron

[Brian Martin]

I have been a Type 1 diabetic for 55 years currently on an insulin pump.  I began using Semaglutide 6 weeks ago without any issues related to the diabetes control.  I have found I eat less and therefore use less insulin. I am still at 0.25mg weekly.  The side effects although improving and still enough to prevent increasing the dose.

[Kristelle Reyes]

Claim your CME here: https://earnc.me/pfKHgV

[Traci Eliszewski]

I am just relistening to the SSRP world congress in Malibu and listened to Dr. Cynthia Keller’s Larazotide talk; I have a type 1 DM patient is who is pretty well controlled, she is RN and very well educated, she was dx with type I after a significant virus in her late 40s, she ended up in the ICU and now type 1 DM. Dr. Keller talked briefly about a young patient with new onset of type 1 DM and she was able to use larazotide, semaglutide, butyrate and a few others to help her cure her type 1 DM. Do you mind sharing the dosing you used with this patient? or in general for those of you using semaglutide in type 1 DM, what is a dose that you like to use? she is very well controlled in general. Not that I want to cure their diabetes, but if anyone has had success with this, I would love input. Thank you!

 

Traci

[Kristelle Reyes]

Hello @andkeller2gmail-com, we would love to have your insights here. Thank you! 🙂

[Traci Eliszewski]

and update on this? thanks! @kristelle

[Telle]

Hello @andkeller2gmail-com, we would love to have your insights here. Thank you! ?

[Traci Eliszewski]

would also love to know the dosing of butyrate supp. she uses as well! thank you!

[Cynthia Keller]

Sorry about the delayed (and now brief ) response… cold and flu season  and now Mastermind 10 have kept me busy (I just arrived home late last night actually)

I will reply more fully soon. But I felt like I couldn’t wait to remind you that it can be life threatening to add a GLP-1 agonist to someone with DM-1 on insulin. Since low glucose is much more dangerous than high glucose acutely.
And, of course, the addition of GLP-1 agonists could/will help reduce the need for the same amount of  insulin. Meaning that they could be thrown into life-threatening hypoglycemia.

So, unless you, and that patient are super savvy, I would not recommend starting this.  Although I do know that some people do so safely, and with good results( see above posts). I am simply wanting to make sure to recommend doing only what is within your scope/skill set.  You know, I always feel the need to be the one to mention… “please be careful”  (it is the pediatrician in me).

In my patient, she had already come off of insulin (which was just being started) before I personally started the semaglutide.

I will reply to the rest of the case/questions soon…

I just wanted to make sure that I was super clear about the above before that (for safety reasons).

again sorry for the delay,

Cynthia

[Traci Eliszewski]

Thank you for  your response! I appreciate it so much.

Do you mind sharing what dose of rectal butyrate you use and for how long? and anyone you wouldn’t necessarily use this in?

thanks!

[Cynthia Keller]

Traci –

 

Sorry again about my delay in response.

About rectal butyrate…..

If you heard me speak at PWC 2023, then you heard me say that there had been a very recent change where the board of pharmacy said that butyrate couldn’t be the “primary” ingredient.  As such…. we needed to have things added to it to get around this.

The pharmacy I use for this (Integrity Pharmacy) , worked me with to get some things added that would work.  See attached order form that Amy (the helpful pharmacist I worked with) got set up for us.

Here is the info she gave me about pricing (as of Aug 2023)

Pricing is below. It does not matter which API is selected or which strength is selected.

Enema

1800mL – $120

3600mL – $180

Suppositories

30 – $75

60 – $132

90 – $198

All prescriptions include free overnight shipping to 46 states (which they ship to).

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As for who to not use in (the second part of your question):

I guess before I would spend that much money I would see if they at least tolerated oral butyrate first.

Almost everyone I know tolerates it, with the exception that some people with significant dysbiosis or UC/Crohn’s often have a hard time tolerating treatments like this  (SCFA/prebiotics) initially until some of the “unwanted” microbiota is beat back a bit.

And of course, the best way to have butyrate there (in the colon) is to have a happy microbiome making the butyrate that you need.

And so, I feel like it is worth mentioning that this isn’t a “forever” treatment, but instead a nice way to help set up a more ideal microbiome.

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I hope this helps.

Cynthia

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