In this week’s issue of The Savvy Diabetic:
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GLP-1s & T1D: How they work, dosing & pharmacokinetics
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Medtronic Recall for Reduced Battery Life
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Breakthrough T1D & TCOYD: Research Highlights
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Sotagliflozin (for CKD) & FDA Advocacy NOW!
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How PBMs Work (30 sec video)
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CVS Breaking Up?
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Non-Diabetics Spend 12% Above Tight Time In Range
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How Tidepool Loop Works
GLP1-RAs in Type 1 Diabetes: more than meets the eye? by Tim Street for Diabettech.com, 8 October 2024.
Some people will be aware, and some not, that there is a reasonable minority of people with Type 1 Diabetes using GLP-1 Receptor Agonists (GLP1-RAs) such as WeGovy and Mounjaro (which is a dual incretin also containing Gastro Inhibitory Polypeptide, GIP), especially in the USA. They are used for a couple of reasons. Often as an antidote to dealing with double diabetes and to aid weight loss, which is often harder for those with type 1 given the demands of exogenous insulin, but also as a mechanism for inhibiting post prandial glucose rises.This article will dig into the latter part of that discussion, and in order to do so, let’s look at the “double bubble” of type 1 diabetes. The missing hormones and extra enzymes that make homeostasis and living a normal life with type 1 that much harder.
Roger Unger, a renowned physician who focused on the role of unopposed glucagon in type 1. His key postulation was that Type 1 Diabetes is as much a condition of excess glucagon as it is of lack of insulin, indeed, if the excess glucagon can be controlled, then insulin requirements become much lower. He successfully demonstrated this with mice (lucky mice), but I don’t believe there were ever human trials of his theories.
Subsequently, Levicure, an Israeli start-up looking to reverse type 1 using readily available therapies has built an amazing model of the mechanism of action of their solution. It’s a little complicated, but it focuses on three points: Inhibiting the immune attack on beta cells without aggressively suppressing the entire immune system; Stopping the metabolic self-damage of beta cells and promoting their regeneration; Increasing insulin secretion while decreasing glucagon secretion. It uses three readily available compounds to do this. DPP-4 inhibitors (Sitagliptin), Proton Pump Inhibitors, and GABA (Gamma-Aminobutyric Acid). The upshot is that by either increasing the availability of GLP1 or increasing the reaction to GLP1, glucagon production is inhibited.
Other Hormones:
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- Amylin: One of the key issues in Type 1 is the lack of various hormones, including Amylin, which reduces the speed at which food passes through the gut. One of the key benefits of GLP1-RAs (indeed, one of the concerns with GLP1-RAs), is that they reduce that rate. In the absence of Amylin, this slowing down of food passage will reduce the rate of absorption of nutrients as the food passes through the intestines, and effectively reduce post prandial highs as a function of this activity.
- Ghrelin: Another malfunctioning hormone in T1D is what’s normally known as the “Hunger” hormone. Ghrelin regulates appetite. More Ghrelin = greater hunger. Within type 1 we have unregulated Ghrelin production. Ghrelin is especially good at encouraging the consumption of sweetened foods, and may play a part in “Hypo Hunger”. One of the key actions of GLP-1RAs is to block Ghrelin receptors in the brain, reducing the feeling of needing to eat.
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Read more: GLP1-RAs in Type 1 Diabetes: more than meets the eye?
GLP1-RAs in Type 1 Diabetes: Dosing and Pharmacokinetics by Tim Street for Diabettech.com, 11 October 2024.
Here we’re going to take a look at the pharmacokinetics (PK) of the two big boys (WeGovy and Mounjaro) and think about the impact those may have on the expected effects with type 1, and potentially the corollary effects when used for other conditions.
Incretin dosing for type 1 management – suggestions: If the variation about the mean with the 7-day dosing period is likely to be problematic for hormone control, then perhaps a reduced dosing period at a smaller dose would make more sense.
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- The way that the different drug concentration varies over time seems to play a part, for some people at least, in the short-term effectiveness of it. Whether this carries over into use in type 1 isn’t clear. It certainly appears from this data that titration may be an important consideration in incretin use.
- Does the difference between the dual incretin make-up of Tirzepatide produce a different set of results to Semaglutide with type 1 users seeking to manage hormones?
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Neither of these is easy to answer, and there’s little data available right now. Both are likely to require either significant real world observation in off-label use, or some form of RCT with careful observation.
Read more: GLP1-RAs in Type 1 Diabetes: Dosing and Pharmacokinetics
Phyiologic Devices is now Portal Diabetes … Fully Automatic Implantable Insulin Delivery!
A dear friend sent me a news release about a company called Portal Diabetes, which just moved from southern CA to Indiana … Portal Diabetes Inc., previously known as PhysioLogic Devices Inc., recently announced its intention to relocate headquarters to Westfield from Southern California.” Portal plans a name change of its signature technology from ThinPump to the Portal Pump. Read about their move: Med-tech company to relocate to Westfield
Founded in 2013, Portal is developing a fully automatic, implantable insulin pump to control glucose levels. The technology will be the first fully automated insulin delivery system that can store up to 12 weeks of insulin through an artificial pancreas. Normal insulin and glucose physiology is restored because the insulin is delivered deep in the abdomen for uptake by the liver. Their approach – fully automatic and implantable – gives people true freedom from the heavy burden of insulin therapy.
For more information, I tracked down The Implantable Insulin Pump Foundation, whose mission is to encourage and support the development of an improved and technologically modern implantable insulin pump that is available in the United States (and throughout the world) and to ensure that this remarkable diabetes management solution is affordable and readily available for any T1D who wants to have it.
Executive Director, Greg Peterson, has lived with T1D for 59 years (hey, same as me!) … and has been using the first implantable insulin pump since January 1992. His story is compelling!
Back in 1992, I was actually scheduled to be patient #11 in the US to receive the implantable insulin pump, by Dr. Jean-Louis Selam, at the University of California, Irvine. But I opted out, as the pump, at that time, was large and lumpy … and I was scared. Well, darn, I wish I had been braver!
Read more:
Medtronic recalls Minimed insulin pumps for reduced battery life by Susan Kelly for MedTechDive.com, 7 October 2024.
Medtronic first alerted customers to a problem with the pumps’ battery status display in July. It found some pumps that were dropped or bumped may have damage to internal electrical components that could reduce battery life. The company initiated a recall on July 31 for more than 785,000 devices. The Food and Drug Administration labeled the recall a Class I event, the severest classification. Medtronic said in its July notice that no serious injuries were confirmed due to the issue.
The October update includes information on reports received by Medtronic and encourages customers to contact the company to determine if a replacement pump is needed. Medtronic emphasized that users should always carry extra batteries and backup insulin therapy and noted that dropping the pump even once could result in reduced battery life, either immediately or over time. The problem could continue after replacing the battery. Escalating alerts and sirens may activate after the “low battery pump” alert. When the “replace battery now” alarm appears, insulin delivery stops. “Do not wait for the later battery alerts as these may occur when less battery life remains than the User Guide states,” the company said.
The notice affects pump models including the Minimed 630G, 670G, 770G and 780G systems. Medtronic said it received 170 reports of hyperglycemia and 11 reports of diabetic ketoacidosis in the U.S., from January 2023 to September 2024, potentially related to the issue.
Read more: Medtronic recalls Minimed insulin pumps for reduced battery life
If you or a loved one are living with type 1 diabetes then you know the literal blood, sweat, and tears that go into managing this 24-hour 365-days-a-year condition. Did you know there is an upcoming FDA hearing to approve the first oral medication for type 1s living with chronic kidney disease to improve glucose control.
Sotagliflozin is a once-daily oral medication that is currently approved by the FDA only in people with type 2 diabetes to improve glycemic control and reduce the risk of a stroke, heart attack, hospitalization, or death from congestive heart failure. Importantly, it is used in people with type 2 diabetes to reduce the progression of chronic kidney disease.
On October 31, Lexicon, the makers of sotagliflozin, will be requesting approval from the FDA for people with type 1 diabetes who have not achieved ideal glucose control and who also have chronic kidney disease—a very common and serious condition that leads to a poor quality of life, increased sickness and premature death. It is personal to me as I have T1D and CKD and want to live a long and healthy life, like all of you.
If approved, sotagliflozin would be the first oral medication approved for those living with type 1 diabetes since the discovery of insulin over 100 years ago.
You have the power to make a difference! If type 1 diabetes and chronic kidney disease have affected your life, or someone you care about, please consider submitting a letter to the FDA using the instructions below. Please note the deadline to submit is October 17!
A Sit Down with Breakthrough T1D’s (Formerly JDRF) CEO Aaron Kowalski by TCOYD.org, 1 October 2024.
This special edition of the Taking Control of Your Diabetes podcast is an enlightening conversation between three diabetes experts all living with type 1 diabetes themselves: Dr. Steve Edelman, Dr. Jeremy Pettus, and Dr. Aaron Kowalski, CEO of Breakthrough T1D (formerly JDRF). They discuss recent research breakthroughs in type 1 diabetes, focusing on three main areas: improving lives through technology and medications, disease-modifying therapies to address the autoimmune nature of type 1 diabetes, and cellular replacement therapies. The conversation highlights advancements in hybrid closed-loop systems, emerging drugs for better glucose control, screening for early detection, and promising stem cell research that could lead to a cure. Dr. Kowalski expresses optimism about the future, suggesting that cell therapy products could be available within this decade, potentially allowing some people with type 1 diabetes to stop requiring insulin.
Listen to the Podcast: A Sit Down with Breakthrough T1D’s (Formerly JDRF) CEO Aaron Kowalski
How PBMs Work by @TheSigmaLife on YouTube.com, 7 October 2024. How they Take Advantage of the Elderly | Joe Rogan.
See the 30 sec video: How They Take Advantage of the Elderly
CVS is under pressure and considering a breakup by Annika Kim Constantino for CNBC.com, 4 October 2024.
Shares of CVS Health are down more than 20% this year as it grapples with higher-than-expected medical costs in its insurance unit and pharmacy reimbursement pressure, among other issues. The company is considering breaking itself up. CVS has engaged advisors in a strategic review of its business. One option being weighed is splitting up its retail pharmacy and insurance units. It would be a stunning reversal for the company, which has spent tens of billions of dollars on acquisitions over the last two decades to turn itself into a one-stop health destination for patients.
CVS risks losing customers and revenue if it splits up its vertically integrated business segments, which include health insurer Aetna and the major pharmacy benefits manager Caremark. That could translate to more lost profits for a healthcare giant that has slashed its full-year 2024 earnings guidance for three consecutive quarters.
Read more: CVS is under pressure and considering a breakup
Normoglycemic Individuals Spend 3 Hours a Day Above Tight Range by Jessica Nye, PhD for EndocrinologyAdvisor.com, 9 October 2024.
Individuals with normoglycemia spend approximately 1.2% of the day with glucose levels above 180 mg/dL and approximately 12.1% of the day with levels above 140 mg/dL, according to study findings published in the Journal of Clinical Endocrinology and Metabolism.
Continuous glucose monitors (CGMs) are available to individuals without diabetes; however, no large-scale studies have assessed glucose trends among the normoglycemic population.
How Tidepool Loop Works by Tidepool.org, 11 October 2024.
The Tidepool Loop app is an FDA-approved hybrid closed-loop system built directly for smartphones and smartwatches. When used together with compatible medical devices, Tidepool Loop works to automatically control the insulin pump to increase, decrease, and suspend delivery of basal insulin based on CGM readings and predicted glucose values, to keep the user’s glucose levels within a user-configurable Correction Range. In this webinar, we dig into what Tidepool Loop takes into account and how it works to keep users in their target correction range.
wow so much here,
The GLP1 information is incredible.
After watching the video, I am ready to sign up for the Portal Diabetes internal pump. Maybe I will knock on the door someday.
The Medtronic recall is unfortunate. However, I have received notice via email and mail. So they are being proactive.
Based on my response to the SGLT2 medication I would say sotagliflozin ought to be approved. My experience is it is really swell.
How do PBM’s work? Let me tell you the ways. I should produce a 30 minute discussion on it and post it to you-tube, i may not get any more medication, but I would feel better.
OOPS maybe i should sell CVS>