#47

Just published: Risk of dementia and Alzheimer’s disease associated with antidiabetics: A Bayesian network meta-analysis

A total of 1,565,245 patients from 16 studies were included. Dementia and AD risks were significantly lower with metformin and sodium glucose co-transporter-2 inhibitors (SGLT2i). Metformin displayed the lowest risk of dementia across diverse antidiabetics, whereas α-glucosidase inhibitors demonstrated the highest risk. SGLT2i exhibited the lowest dementia risk across second-line antidiabetics. Dementia risk was significantly higher with dipeptidyl peptidase-4 inhibitor (DPP4i), metformin, sulfonylureas and thiazolidinediones (TZD) compared to SGLT2i in the elderly (≥ 75 years). Dementia risk associated with metformin was substantially lower, regardless of diabetic complication status or baseline A1C.

(α-glucosidase inhibitors = acarbose, miglitol, voglibose, etc.)

It doesn’t mean that acarbose causes dementia, it could be a reverse causality: maybe large glucose spikes and excursions cause dementia and people with such glycemic profile are prescribed acarbose more (especially in the West) compared to people with a high average glucose but a low variability.

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Predicting Alzheimers & Dementia (and minimizing risk)
#48

So Acarbose may not be superior to Metformin when it comes to dementia. Good to know.

I’ll stick with my Metformin and SGLT2I, then.

I don’t want to be a long lived vegetable.

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#49

I feel that I should add to this thread that anyone into recreational flatulence would really enjoy acarbose. It is in a class by itself.

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#50

Yes, teenage boys would probably love the side effects :grin:

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#51

I realise the point here is humor but I’d like to add that I experienced no increased flatulence on acarbose after about a week. I think it must be down to diet and I don’t eat any wheat.

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#52

I frequently take Acarbose with slices of bread and don’t experience any side effects :person_shrugging:

My diet is plant based for years so I have a different gut than most people, though.

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#53

Perhaps your baseline of flatulence is already at the maximum?

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#54

Bummer. You are missing out.

#55

Same here. Never had issues with gas from taking ACA. I take 100 before a meal that has carbs (pasta, pizza, sweets etc) and never noticed any bloating.

#56

I think your gut biome adjusts over time. When I first started taking acarbose the side effects didn’t seem worth it. At first, I adjusted my diet, avoiding wheat products because that seemed to exacerbate the problems. After a few months, the side effects went away.

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#57

I used to get a large amount of flatulence with Acarbose, and then I had a colonoscopy. The bowel preparation wipes out most of the micro biome from what I could tell ( hopefully all the bad stuff whilst some good bacteria cling on). Since then, no flatulence at all.
(State of passing stools also normalised from previously rock hard pebbles no matter how much fibre I consumed).
Makes me think those with a poor micro biome might be better off taking the bowel prep medication even if they don’t have a colonoscopy.

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#58

This almost killed me. I took it one tablet before meals for couple days and I was bed ridden with kidney, liver and heart pain for over 24 hours. Initially thought the culprit must have been RAPA since It coincided that I started taking these pills same time I started RAPA after i did 3 months clean up time. At some point I thought I might have had small heart attack because I have so severe chest pain that i had to breath very slowly. I should have read on one-star reviews where people were reporting same exact issue. Disgusting that these things are put in the market without a safety evaluation.

no offense but for anyone that suggest such dangerous product (even though not much of your fault since maybe for you it worked), I have to put you in ignore and will NEVER read your posts again. In my way thinking I have come to realize in here and in life dealing with some people you will have ONLY negative outcomes. Anyway, guys ALWAYS read one-star reviews as those are the only ones that matter.

#59

I take 3 or 4 before a meal with carbs… nothing. Sometimes in the morning, if I had it for the evening meal the night before, I have a gut ache until I eat something. Food fixes it. Otherwise I get nothing.

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#60

Do you or someone else have access to the full paper? I wonder if they controlled for A1C. Mechanistically, it’s hard to explain greater risk from acarbose. The risk of hypoglycemia should be lower compared to other agents.

Reverse causation as you described is possible. As are selection effects due to acarbose being an older and cheaper drug. Also, acarbose may just be less effective in terms of its antidiabetic effect than other agents, especially with a Western diet.

Separately, it would be interesting to see the effect sizes and how many years of data they used / what kind of delay was used between start of treatment and incident AD. Notably, GLP-1s and SGLT2is have not been widely used for that long.

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#61

No sorry. On acarbose & AD risk/prevention, see also:

#62

How do you interpret: “SGLT2i exhibited the lowest dementia risk across second-line antidiabetics. Dementia risk was significantly higher with … metformin … compared to SGLT2i in the elderly (≥ 75 years).”
So metformin is the best, but still worse than SGLT2i? Or only in over 75 year olds? Perhaps I don’t understand “second-line antidiabetics”?

#63

Metformin is a very old medication… so I think its considered “first generation”, or “first line” as it was probably the first major medication for diabetes, and the most commonly used medication for diabetes.

The SGLT2 inhibitors are newer, coming on the market a decade ago or so, so they are considered second-line medications in the treatment of diabetes.

It sounds like the SGLT2 inhibitors are the best option, with better performance than metformin (in the elderly). There may be a study of these medicines in people over the age of 60 to 75 (a younger cohort) that I’m not aware of, but I haven’t looked.

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#64

So “Metformin displayed the lowest risk of dementia across diverse antidiabetics,” refers to first line ones only?

I thought first line “of defense” is given first to a patient, like telmisartan before amlopidine, or metformin before SGLT2i still is today.

#65

I’m not sure where you’re getting that quote from - can you link to the paper you’re quoting?

#66

It is just one sentence above the first quote. That is why I am confused.
" Metformin displayed the lowest risk of dementia across diverse antidiabetics, whereas α-glucosidase inhibitors demonstrated the highest risk . SGLT2i exhibited the lowest dementia risk across second-line antidiabetics. Dementia risk was significantly higher with dipeptidyl peptidase-4 inhibitor (DPP4i), metformin,…"