@DrFraser I agree. I only take it to combine with rapamycin. For blood sugar control and other benefits I rely on berberine and Akkermansia.
Metformin taken regularly make HIIT exercise much harder. It is probably interfering with mitochondria function and forcing my type 2 muscle fibers to burn glucose without oxygen resulting in higher lactate and hydrogen.
For a person that does not have diabetes, I’ll agree.
For me who is teetering on the very edge of diabetes I was waiting until I start w/ rapamycin to combine with Metformin.
“Rapamycin and metformin combination treatment in a mouse model of type 2 diabetes, NONcNZO10/LtJ males, prevents hyperinsulinemia, normalizes insulin sensitivity, and reduces pathological complications of diabetes. When combined, each compound prevents the negative side effects of the other. These results are relevant for the treatment of diabetes, the optimization of current rapamycin‐based treatments, and the development of treatments for healthy aging.”
Thoughts or suggestions for someone who is clearly moving towards diabetes and doesn’t want to go there?
Depends on other risks/conditions/contraindications - but Acarbose is one option. If you have no contraindication, an SGLT2-i is something to review with your physician (I know most people won’t get good feedback there) … but given the likelihood that these agents dually have neurocognitive decline benefit and other aging benefits … I’ve got a new appreciation for this class of medications. The more I read, the more I like what I see.
Working in the ER and having seen a couple of complications with the SGLT2-i’s (albeit only in diabetics with lots of other health issues)- I was initially not that eager to jump in - but looking at the actual numbers, and the risk/benefit … apart from cost if you are not sourcing them outside of a U.S. pharmacy - it is worthy of a review.
Again, no medical advice, just my general thoughts on things to consider.
I am also questioning my use of metformin. After taking metformin for decades my body seems to be growing intolerant of it. I have cycled on and off of metformin in the last couple of years to see what the effects of metformin are. Now I have found that metformin consistently causes me to have a sour stomach. I have had to cut down my dose to once a day with my largest meal.
When I have cycled off I found that I could just as effectively control fasting glucose levels with a variety of other supplements such as berberine. I also take acarbose.
I have continued to take metformin because of its supposed synergistic effect when used for life extension. The evidence is weak, especially for older people.
I am a huge fan of Akkermansia. It is the only thing that has gotten my HbA1c to normal levels (5.0). I was 5.5-5.8 for 20 years. Low carb, no sugar, berberine, metformin…nothing moved it my more than a couple tenths. Akkermansia does something amazing for my body.
Have you tried the extended release vs the immediate release? Same acid stomach symptoms?
I’ve only perused acarbose a bit but it does seem impressive. Though, I can’t get the image of the side effects of Orlistat out of my mind.
On most days I keep below a net 20 grams carb. Since Acarbose works on carbs how effective will it be for a person on strict keto?
For a SAD eater ingesting 100-200 grams of carbs, when those carbs cannot get used, they become fodder for the bugs, which may be a good thing but I’m imagining +2 degrees to CO2 worldwide due to expressed gas… 
How are the side effects of Acarbose?
Certainly most of the effect of acarbose is simply as an agent that inhibits alpha-amylase and intestinal alpha-glucosidase. So the biggest effect is slowing carbohydrate absorption. So if you have very few, then the drug would be unlikely to generate much results or side effects. Even in high carb eaters - most start low dose and wean up and have tolerability - depending on diet/gut flora, etc.
You might want to take a look at the SGLT2-inhibitors and review some literature on those - as this can be a consideration if wanting to avoid metformin.
Again, have a chat with your doctor on this - but that would be one area to look into - but I suspect the acarbose would not have the same efficacy in you with a low carb diet.
No, I haven’t tried it. Next time I see my doctor I will ask him about it.
Check out figure 4 in this:
I could “take a look,” at the SGLT2 inhibitors but not much more at $400+/month.
It was pulling teeth to get my Practitioner (a PA) to prescribe extended-release metformin.
Just yesterday, I pulled a 12-hour overnight fasting BG of 149. Yet my last A1C was “in the green,” at 5.6, albeit at the upper end. I look at that as just awful, but he seems to look only at the A1C. I don’t want to do so many days of water fasting to keep that A1c down.
Being on Medicare, I suspect there would be no way that insurance would pay for it, and no way that my PA would prescribe it.
On the other hand, Jardiance through Indiamart comes in at about $0.60/tablet in either 10 or 25mg.
What a sick world America is, the same med, in America at $13-/tablet from India at $0.60 only a 22x difference!
With my A1C “in the green,” but morning FBGs of 130-160 I look at this is being horrid, and something to fix. My PA simply says: “Lose weight, work out…” My response: “I’ve lost 54lbs over the past year and do 150-200 mins/wk cardio + ~5 hours lifting and my BG has not changed a bit—nor has my BP, to my chagrin. My lack of improvement mystifies me.
Luckily, with a A1c of 5.6 I don’t feel too pressed for time. I’ll keep off the Metformin for the time being since I’m so happy building back after my “second chance,” due to successful surgery.
One step at a time, I think, start low, go slow. And I do not want to stay strict keto forever…
Metformin extended release appears to have significantly fewer side effects and greater efficacy.
Maybe one of the doctors on the forum could answer why the extended-release is not more commonly prescribed than the immediate release.
Justin - you are expressing the frustration of people who are proactive - but the system needs to see disease before they understand the need to treat.
A brief piece of advice - get a fasting insulin done paired with a fasting glucose. That is what will help you sort out what is going on. If your insulin is (normal) e.g. <20 and your fasting sugar is >100 mg/dL - basically, you are doing what I see is common place in older individuals. Your pancreas set point is such that it is not responding appropriately by secreting insulin until your blood sugar is higher than it should be. What we know in that situation is exercise and weight loss won’t help the situation much. Meds will be required.
If however you have a high fasting insulin - appropriate for the blood sugar being elevated - then the issue is insulin resistance and a different strategy is undertaken. Then your PA’s advice would be valid. Without a paired insulin and glucose … we have no idea.
This calculator will calculate the HOMA-IR and give you some interpretation:
https://www.mdcalc.com/calc/3120/homa-ir-homeostatic-model-assessment-insulin-resistance
Hopefully this makes sense.
Even if your PA doesn’t agree to Rx you an SGLT2-i … you can certainly ask them if they think there is a reason with your medical history that it would be unsafe to take one? If not - even if they won’t Rx it - you seem to know how to get these … and depending on insulin-glucose = Homa-IR results there may be a better option (usually not).
Next thing - the keto diet isn’t a good choice - it is short term chasing a number, but long term likely to worsen every health outcome …. Take a look at Neal Barnard of the Physician’s Committee on his lectures on diet and diabetes. Page - Watch the Video.
Even if you don’t implement that fully - it will give you a very good basis to understand how a healthy, high complex carb diet is actually best for most patients with T2DM - and actually reverses disease in many. In the short term it may make your glucose go a bit higher - but that will settle and be better than on a keto.
On 1/30, after my PCP told me that, “no, he would not prescribe a HOMA-IR because it “did not predict anything, reliably,” So, I went to my local lab and did the Quest Cardia-IQ for $50. My fasting insulin was 3. My C-Peptide was 1.26, my fasting BG was 135. The Cardio-IQ gave me an insulin resistance score of 6 on a scale of 1-100 with less than 33 as optimal.
Therefore, I’m very insulin sensitive. I was quite shocked and had hoped to see even a score of 50. Over the five months preceding that test I had done 40 days of water fasting, in mostly one and two-day water fasting with some 3-day and one 4-day water fasts. The other days less than 10-15 net carbs.
As you stated: “Your pancreas set point is such that it is not responding appropriately by secreting insulin until your blood sugar is higher than it should be. What we know in that situation is exercise and weight loss won’t help the situation much. Meds will be required.”
Interestingly, playing with a CGM and realizing that I seem to have a very (improperly) robust “dawn phenomenon,” I’ve found that eating when I get up (rather than skipping breakfast, which I normally do) pushes my BG up a small amount, and then it drops to below 125 an hour or so later. But to have a low of 120 is not a good thing. I had hoped/expected that after losing 50+ lbs I’d see a fasting BG of 85. Ouch.
The calculator gives a “1,” where 2+ indicates insulin resistance, so there, also, I’m insulin sensitive.
It seems a rather odd physical setup, almost irrational.
Looking back to ““Your pancreas set point is such that it is not responding appropriately by secreting insulin until your blood sugar is higher than it should be. What we know in that situation is exercise and weight loss won’t help the situation much. Meds will be required.”
Have you any ideas or directions that I can read up on just what’s going on here? It’s not tired beta cells, it’s not insulin resistance, so what is going on? It seems that for most, it’s insulin resistance.
I will look into the SGLT2-inhibitors. I had tried to book an appointment w/ a endocrinologist, but there appears to be a shortage and no appointment for many months. And even there, I wonder—not all Practitioners care to deal with folk that are curious and who read.
I watched Neil Barnard’s talk and under it there were two comments that rang “true.”
—"I just watched two TED talks on diabetes, one after the other. The first said “cut-out carbs, eat fats”. The second said “cut-out fats, eat carbs”.
—This is AMAZING. There are 20 people on the internet, all with drastically different approaches and they ALL cure diabetes.
Being on keto felt good, but perhaps more critical in my case, being on keto made water fasting very, very easy and that was how I lost the 54lbs.
Again, thank you for the excellent feedback.
Cost? Extended release is about double the cost but that’s 60 cents a day versus 21 cents a day, so yours’ is a good question, I think.
I specifically asked my Practitioner for extended because if you look at the pharmacodynamic curve, I could take it (extended does not need a meal) at a time such that my blood level would be at a low when I worked out at the gym.
I had hypothesized that doing so might mitigate the blunting of muscle hypertrophy.
Admittedly it likely would not bring my A1C down as much as taking one every 12 hours.
Note: I’ve added this a few hours after the above post. I was taking a 3-hour nursing CEU course on diabetes meds and came across this:
“Metformin XR is slowly absorbed, it produces a therapeutic level of the drug over a 12 to 24-hour period, and this means that metformin XR needs only to be taken once per day (Akram, 2021).”
Now I wonder if there is rapid acting extended release which has an effect over 12 hours versus what is implied above, that it would last 24 hours…
For you, I think this would not matter, but for my issue of Metformin and muscle hypertrophy well, yes.
So your PCP is incorrect. You cannot give someone advice on what to do without knowing insulin sensitivity. You can presume that someone who is a typical T2DM who is obese and sedentary is insulin resistant. You’ll be right almost all the time.
The issue is, that a lot of patients who then truly put effort in, and improve themselves (e.g. weight loss, exercise), but at the end still have blood sugars that aren’t coming in properly - end up doing exactly as you’ve had happen. This is part of aging.
It is important as a PCP to understand this, as the advice you then give to the patient is different. Even the drugs you might use would be different - for example, prescribing a drug that primarily improves insulin sensitivity - when you are already sensitive will do little! If they continue to give you advice assuming your issue is insulin resistance - you’ll never get anywhere - and you’ll try all types of stupid diets and other things, which will never do anything effective to your blood sugar, and will worsen your health outcomes.
Patients who are insulin sensitive and running high fasting sugars and have made lifestyle changes seem to mostly be older individuals - and the answer is to stop doing silly things - optimize your health realizing the options for your blood sugar at this point are medication - or let the numbers run untreated.
Just my experience … and ignore the morons on social media with stuff to sell you, which can be as simple as selling you themselves. The researchers are the experts, and the medical evidence is pretty solid for Neil’s approach. Plus, your diet isn’t going to be a major influence on your numbers - as your pancreas is happy standing by and not responding to a blood sugar of 130. I find that individuals like yourself just have a different setpoint - put you up to a glucose of 180 and your pancreas has no problem pouring out plenty of insulin.
So you might as well have a diet that maximizes health benefits, but realize that Neil’s approach also is unlikely to make any difference to your diabetes - apart from the health benefits of a healthy diet on cognition, heart disease, cancer risk. It will decrease intramyocyte fat - which will help peripheral insulin uptake which can help - but your primary issue is your pancreas is chilled out and happy watching a blood sugar that it should be reacting to.
Important point - if you choose to change your diet - you need to do it gradually - track by current dietary fiber, and increase by no more than 5 g/day fiber on a weekly basis - goaling for at least 40 grams/day … but do it slow as your gut bacteria need time to gradually respond.
Again, just my general perspective and not medical advice. Discuss with your PCP … but sadly they are going to advise T2DM incorrectly and not manage them optimally if, in your situation they don’t know your insulin resistance.
One last thing - a good PCP learns from patients - and it influences and benefits all their patients henceforth. There is too much to know - being humble and learning is the sign of a great mind. So my question I’d put forth to a physician in this situation is:
Given that insulin resistance isn’t my issue, and sarcopenia clearly is a risk for poor health outcomes. Can you advise on your strategy in thinking about pharmacotherapy in an insulin sensitive patient who has ongoing elevated blood sugars - who also is probably not a Type IIIC diabetic, but simply has a pancreas not willing to respond until glucose levels are higher than optimal.
Also, naturally, let them know that you don’t expect an immediate answer, and you’d love for them to investigate, and get back with you.
The good news with you - is that you don’t have high insulin levels - as this is independently toxic to blood vessels - which is why strategies such as sulfonylureas and insulin don’t look good for longevity. But the modest hyperglycemia, will be a vascular and cognitive risk. But everything is relative. I have several patients in exactly this situation. It’s easy for me to optimize them - but I have a couple who are still seriously trying to fix this with lifestyle. I’ve told them that this won’t work - they still persist … and it won’t work. They are already at good BMI, lots of physical activity - great things to continue with — but the thought that this will help their blood sugar of 140 mg/dL when their fasting insulin is 5 … just isn’t going to happen. Anyway, I can only advise.
Thank you DrFraser
So, I have the dreaded CPS (chilled pancreas syndrome). Oh my.
There’s much that I am thankful for. A borderline, but acceptable A1c with high BG for parts of the day, well, a lot of folks would give a lot to see FBG of 155 with an A1C that equates to an overall 3-month BG average of about 123.
My being sensitive to insulin is a real +. I wish that I had the numbers from a year ago to see if/what changed.
In an ideal world my PCP might be a resource, but here, alas, it won’t happen. The whole system I’m in is overworked and understaffed—they do their best, I’m sure.
I’ll schedule a consult with an endocrinologist who, at least, should be more familiar with what’s going on and how to fix it.
So, I’m back, full circle to Metformin. In my case it won’t help by increasing insulin sensitivity but it will decrease intestinal absorption of glucose and decrease hepatic glucose production and I sense that every bit helps. Perhaps I’ll aggressively increase my cardio and weight-lifting for some months and then start Metformin.
I’ll also work on both fiber, diet and as Joseph_Lave suggested look into gut biota, especially Akkermansia.
I’m off to read this
I’ve had luck with metformin/acarbose in patients with this - even though neither should really work. Theoretically something that either gets rid of a bit of glucose - primarily an SGLT2-inhibitor or something that causes your pancreas to increase secretion of insulin would be the logical approach - at least with my understanding (such as a DPP-4). The concern I’d have with something like a sulfonylurea - which is cheap and causes increased insulin secretion - is the propensity to cause weight gain, and also an increased risk - especially in someone with a pretty good HbA1C to cause hypoglcymia.
Looking at dual treatment - e.g. glycemic risk and cognitive decline risk - I’d think one might favor an SGLT2-inhibitor - but certainly a discussion with the endocrinologist seems a wise move. They however are unlikely to look at dual use and focus on only the endocrine issue.
Hopefully my input allows you to frame the discussion with the endocrinologist and ask the questions that will help guide best treatment.
Never heard of that. What is it?
I suspect this was in reference to the statement that his pancreas was chilled out and totally happy watching a blood glucose of 130 mg/dL and not doing anything about it. I do however like his label of it.