Latest Update on Metformin

[mcs]

Observations being on ER-Metformin for last 4.5 mos.
(started July 1, 2022)​

1. 15lbs weight loss - no change in diet or training
2. No GI problems up to 2g/day
3. No change in fasting glucose levels or a1c (not diabetic to begin with)
4. *Substantial decrease in total and free T (not on TRT):
   
   • June, 2022 (pre-Metformin): TT: 553; FT: 76.9
   • August, 2022 (1 month Metformin): TT: 415; FT: 70.2
   • November, 2022 (4 months Metformin): TT: 318; FT: 61.7
5. No difference in aerobic or resistance training
6. Slight decrease in IGF-1 (which I don't mind because mine was already high normal @ 250)
7. B12 is still over range (because I supplement with 1-2mg/day!)

*I was always on the fence about TRT but now since the Metformin has tanked my levels, maybe this is the push I need? The only problem is I have hypertension and had clotting issues in the past, both of which I'm managing with meds (telmisartan, nebivolol, rivaroxaban), but the hypertension is on the top of my list of TRT side effects and BP is still not where I'd like to see it (120/80 or less). 62 y/o male.

Thoughts?

 

[Vince]

Observations being on ER-Metformin for last 4.5 mos.
(started July 1, 2022)​

1. 15lbs weight loss - no change in diet or training
2. No GI problems up to 2g/day
3. No change in fasting glucose levels or a1c (not diabetic to begin with)
4. *Substantial decrease in total and free T (not on TRT):
   
   • June, 2022 (pre-Metformin): TT: 553; FT: 76.9
   • August, 2022 (1 month Metformin): TT: 415; FT: 70.2
   • November, 2022 (4 months Metformin): TT: 318; FT: 61.7
5. No difference in aerobic or resistance training
6. Slight decrease in IGF-1 (which I don't mind because mine was already high normal @ 250)
7. B12 is still over range (because I supplement with 1-2mg/day!)

*I was always on the fence about TRT but now since the Metformin has tanked my levels, maybe this is the push I need? The only problem is I have hypertension and had clotting issues in the past, both of which I'm managing with meds (telmisartan, nebivolol, rivaroxaban), but the hypertension is on the top of my list of TRT side effects and BP is still not where I'd like to see it (120/80 or less). 62 y/o male.

Thoughts?

What is your fasting? Glucose and your A1C.

 

[Nelson Vergel]

Thanks for the detailed encouraging report. If you have BP issues, TRT may be a problem.

How much do you weigh now and how tall are you ?

Have you had genetic testing for the clotting issue ?

 

[mcs]

What is your fasting? Glucose and your A1C.

low 100s if I don't fast for at least 12h, in the mid to high 90s if I do. If I eat even complex carbs for dinner, FBG will go into the 110-115. A1C 4.9-5.2. Metformin doesn't seem to influence those numbers either way. I take 1g with last meal and 500mg before sleep.

 

[mcs]

Thanks for the detailed encouraging report. If you have BP issues, TRT may be a problem.

How much do you weigh now and how tall are you ?

Have you had genetic testing for the clotting issue ?

5-7 180lbs - but even when I weighed 20lbs less, my BP did not lessen.
Have tested my DNA extensively for hereditary clotting issues and nothing came up except MTHFR. I feel I need be on TRT at this point and think I should d/c the Metformin for now until my T levels are optimized. Maybe start with low-dose of T like 30mg EOD (112.5mg/week)?

 

[Vince]

low 100s if I don't fast for at least 12h, in the mid to high 90s if I do. If I eat even complex carbs for dinner, FBG will go into the 110-115. A1C 4.9-5.2. Metformin doesn't seem to influence those numbers either way. I take 1g with last meal and 500mg before sleep.

Does your labs tell your average glucose reading?

 

[mcs]

Does your labs tell your average glucose reading?

My glucometer app does:

 

[mcs]

My joint pains have worsened to which I attribute both low T and E2 symptoms. I think it's obvious I should d/c the Metformin until I get my hormones optimized.

 

[Deleted member 43589]

Observations being on ER-Metformin for last 4.5 mos.
(started July 1, 2022)​

1. 15lbs weight loss - no change in diet or training
2. No GI problems up to 2g/day
3. No change in fasting glucose levels or a1c (not diabetic to begin with)
4. *Substantial decrease in total and free T (not on TRT):
   
   • June, 2022 (pre-Metformin): TT: 553; FT: 76.9
   • August, 2022 (1 month Metformin): TT: 415; FT: 70.2
   • November, 2022 (4 months Metformin): TT: 318; FT: 61.7
5. No difference in aerobic or resistance training
6. Slight decrease in IGF-1 (which I don't mind because mine was already high normal @ 250)
7. B12 is still over range (because I supplement with 1-2mg/day!)

*I was always on the fence about TRT but now since the Metformin has tanked my levels, maybe this is the push I need? The only problem is I have hypertension and had clotting issues in the past, both of which I'm managing with meds (telmisartan, nebivolol, rivaroxaban), but the hypertension is on the top of my list of TRT side effects and BP is still not where I'd like to see it (120/80 or less). 62 y/o male.

Thoughts?

Here is some material to read over

Metformin Lowers Testosterone?

I have been taking Metformin for just the benefits. For the past year, I am not diabetic. I was not under the impression that it lowers your testosterone. I was informed by my doctor that it lowers your testosterone. And I also jumped online and looked apparently it does. I don’t know if this is...

www.excelmale.com

 

[Biobro]

Metformin, besides exhibiting strong in vivo anti-inflammatory properties, increases mptp-induced damage to the nigrostriatal dopaminergic system​

Metformin, besides exhibiting strong in vivo anti-inflammatory properties, increases mptp-induced damage to the nigrostriatal dopaminergic system - PubMed

Metformin is a widely used oral antidiabetic drug with known anti-inflammatory properties due to its action on AMPK protein. This drug has shown a protective effect on various tissues, including cortical neurons. The aim of this study was to determine the effect of metformin on the dopaminergic...

pubmed.ncbi.nlm.nih.gov

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Metformin Repurposing for Parkinson Disease Therapy: Opportunities and Challenges​

Conclusions​

Several works recently suggested that metformin may be used as a promising therapeutic strategy to counteract the progression of neurodegenerative disorders, including PD. However, despite intensive research, the precise mechanisms by which metformin exerts its activity are not completely understood. Therefore, to determine the potential therapeutic use of metformin as a disease modifier for PD, it is crucial to evaluate its main pharmacological properties, such as the bioavailability in the brain, the molecular pathways it affects, and the concentrations necessary to observe the beneficial effects. Unfortunately, the data available in the literature are often controversial and vary significantly among experimental models, prompting the necessity to outline a consensus in pre-clinical data interpretation.

At the same time, the prolonged consumption of metformin at a relatively high dosage might induce serious side effects that could worsen the risk of developing PD over time. In this frame, the epidemiological studies that investigated the association between metformin therapy and PD only assessed the effect of the drug in T2DM patients [65,66,67,68,69].

Metformin Repurposing for Parkinson Disease Therapy: Opportunities and Challenges - PMC

Parkinson disease (PD) is a severe neurodegenerative disorder that affects around 2% of the population over 65 years old. It is characterized by the progressive loss of nigrostriatal dopaminergic neurons, resulting in motor disabilities of the ...

www.ncbi.nlm.nih.gov

Hypothesis: Metformin is a potential reproductive toxicant​

Hypothesis: Metformin is a potential reproductive toxicant - PubMed

Metformin is the first-line oral treatment for type 2 diabetes mellitus and is prescribed to more than 150 million people worldwide. Metformin's effect as a glucose-lowering drug is well documented but the precise mechanism of action is unknown. A recent finding of an association between...

pubmed.ncbi.nlm.nih.gov

Metformin Linked to More Severe Neuropathy Pain​

Metformin Linked to More Severe Neuropathy Pain - DSM

In a new study, taking metformin for a long period was linked to lower vitamin B12 and, perhaps as a result, more severe pain from diabetic neuropathy.

www.diabetesselfmanagement.com

 

[Biobro]

Just curious are you guys still using metformin nowadays?

 

[Deleted member 43589]

Thanks for posting this @Bibro. Very interesting stuff. By the way, I use it off and on. I have to eat a huge amount of calories to keep my weight but when I take metformin the weight comes off quickly. So I have to be careful how long I am on it.

 

[Vince]

Just curious are you guys still using metformin nowadays?

Yes, I'm a long term metformin user. I believe I've been using it now for over 10 years. I use it for longevity benefits. It does keep my A1C at 5.1. I'm hoping to get it lower than 5.

 

[Biobro]

Thanks for posting this @Bibro. Very interesting stuff. By the way, I use it off and on. I have to eat a huge amount of calories to keep my weight but when I take metformin the weight comes off quickly. So I have to be careful how long I am on it.

Gotcha! Does it give you any side effects?
I’ve been playing around 500mg ER dosages once daily lately. Makes me too relaxed, lazy and gives me constipation.
And because of the studies i dont think im gonna continue that experiment anymore.
Far better alternatives out there, example semaglutide.

 

[Biobro]

Yes, I'm a long term metformin user. I believe I've been using it now for over 10 years. I use it for longevity benefits. It does keep my A1C at 5.1. I'm hoping to get it lower than 5.

Wow 10 years. How you feel on it? Any side effects?

 

[Vince]

Wow 10 years. How you feel on it? Any side effects?

The only side effect was it did lower my B12. So I just increased my dose of B12. I do get all my b vitamins levels checked and now they are all in a good range.

 

[Biobro]

I use it for longevity benefits.

And you probably know that those longevity benefits has been repealed on high risk type 2 diabetes patients and placebo in latest studies. But of course it preventing you becoming type 2 diabetic.

Effect of Metformin and Lifestyle Interventions on Mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study​

Christine G Lee et al. Diabetes Care. 2021 Dec.

Abstract​

Objective: To determine whether metformin or lifestyle modification can lower rates of all-cause and cause-specific mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study.
Research design and methods: From 1996 to 1999, 3,234 adults at high risk for type 2 diabetes were randomized to an intensive lifestyle intervention, masked metformin, or placebo. Placebo and lifestyle interventions stopped in 2001, and a modified lifestyle program was offered to everyone, but unmasked study metformin continued in those originally randomized. Causes of deaths through 31 December 2018 were adjudicated by blinded reviews. All-cause and cause-specific mortality hazard ratios (HRs) were estimated from Cox proportional hazards regression models and Fine-Gray models, respectively.
Results: Over a median of 21 years (interquartile range 20-21), 453 participants died. Cancer was the leading cause of death (n = 170), followed by cardiovascular disease (n = 131). Compared with placebo, metformin did not influence mortality from all causes (HR 0.99 [95% CI 0.79, 1.25]), cancer (HR 1.04 [95% CI 0.72, 1.52]), or cardiovascular disease (HR 1.08 [95% CI 0.70, 1.66]). Similarly, lifestyle modification did not impact all-cause (HR 1.02 [95% CI 0.81, 1.28]), cancer (HR 1.07 [95% CI 0.74, 1.55]), or cardiovascular disease (HR 1.18 [95% CI 0.77, 1.81]) mortality. Analyses adjusted for diabetes status and duration, BMI, cumulative glycemic exposure, and cardiovascular risks yielded results similar to those for all-cause mortality.
Conclusions: Cancer was the leading cause of mortality among adults at high risk for type 2 diabetes. Although metformin and lifestyle modification prevented diabetes, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates.

Effect of Metformin and Lifestyle Interventions on Mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study - PubMed

Cancer was the leading cause of mortality among adults at high risk for type 2 diabetes. Although metformin and lifestyle modification prevented diabetes, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates.

pubmed.ncbi.nlm.nih.gov

Effects of Long-term Metformin and Lifestyle Interventions on Cardiovascular Events in the Diabetes Prevention Program and Its Outcome Study​

Originally published 23 May 2022

Background:​

Lifestyle intervention and metformin have been shown to prevent diabetes; however, their efficacy in preventing cardiovascular disease associated with the development of diabetes is unclear. We examined whether these interventions reduced the incidence of major cardiovascular events over a 21-year median follow-up of participants in the DPP trial (Diabetes Prevention Program) and DPPOS (Diabetes Prevention Program Outcomes Study).

Methods:​

During DPP, 3234 participants with impaired glucose tolerance were randomly assigned to metformin 850 mg twice daily, intensive lifestyle or placebo, and followed for 3 years. During the next 18-year average follow-up in DPPOS, all participants were offered a less intensive group lifestyle intervention, and unmasked metformin was continued in the metformin group. The primary outcome was the first occurrence of nonfatal myocardial infarction, stroke, or cardiovascular death adjudicated by standard criteria. An extended cardiovascular outcome included the primary outcome or hospitalization for heart failure or unstable angina, coronary or peripheral revascularization, coronary heart disease diagnosed by angiography, or silent myocardial infarction by ECG. ECGs and cardiovascular risk factors were measured annually.

Results:​

Neither metformin nor lifestyle intervention reduced the primary outcome: metformin versus placebo hazard ratio 1.03 (95% CI, 0.78–1.37; P= 0.81) and lifestyle versus placebo hazard ratio 1.14 (95% CI, 0.87–1.50; P = 0.34). Risk factor adjustment did not change these results. No effect of either intervention was seen on the extended cardiovascular outcome.

Conclusions:​

Neither metformin nor lifestyle reduced major cardiovascular events in DPPOS over 21 years despite long-term prevention of diabetes. Provision of group lifestyle intervention to all, extensive out-of-study use of statin and antihypertensive agents, and reduction in the use of study metformin together with out-of-study metformin use over time may have diluted the effects of the interventions.

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.056756

 

[Vince]

And you probably know that those longevity benefits has been repealed on high risk type 2 diabetes patients and placebo in latest studies. But of course it preventing you becoming type 2 diabetic.

Effect of Metformin and Lifestyle Interventions on Mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study​

Christine G Lee et al. Diabetes Care. 2021 Dec.

Abstract​

Objective: To determine whether metformin or lifestyle modification can lower rates of all-cause and cause-specific mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study.
Research design and methods: From 1996 to 1999, 3,234 adults at high risk for type 2 diabetes were randomized to an intensive lifestyle intervention, masked metformin, or placebo. Placebo and lifestyle interventions stopped in 2001, and a modified lifestyle program was offered to everyone, but unmasked study metformin continued in those originally randomized. Causes of deaths through 31 December 2018 were adjudicated by blinded reviews. All-cause and cause-specific mortality hazard ratios (HRs) were estimated from Cox proportional hazards regression models and Fine-Gray models, respectively.
Results: Over a median of 21 years (interquartile range 20-21), 453 participants died. Cancer was the leading cause of death (n = 170), followed by cardiovascular disease (n = 131). Compared with placebo, metformin did not influence mortality from all causes (HR 0.99 [95% CI 0.79, 1.25]), cancer (HR 1.04 [95% CI 0.72, 1.52]), or cardiovascular disease (HR 1.08 [95% CI 0.70, 1.66]). Similarly, lifestyle modification did not impact all-cause (HR 1.02 [95% CI 0.81, 1.28]), cancer (HR 1.07 [95% CI 0.74, 1.55]), or cardiovascular disease (HR 1.18 [95% CI 0.77, 1.81]) mortality. Analyses adjusted for diabetes status and duration, BMI, cumulative glycemic exposure, and cardiovascular risks yielded results similar to those for all-cause mortality.
Conclusions: Cancer was the leading cause of mortality among adults at high risk for type 2 diabetes. Although metformin and lifestyle modification prevented diabetes, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates.

Effect of Metformin and Lifestyle Interventions on Mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study - PubMed

Cancer was the leading cause of mortality among adults at high risk for type 2 diabetes. Although metformin and lifestyle modification prevented diabetes, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates.

pubmed.ncbi.nlm.nih.gov

Effects of Long-term Metformin and Lifestyle Interventions on Cardiovascular Events in the Diabetes Prevention Program and Its Outcome Study​

Originally published 23 May 2022

Background:​

Lifestyle intervention and metformin have been shown to prevent diabetes; however, their efficacy in preventing cardiovascular disease associated with the development of diabetes is unclear. We examined whether these interventions reduced the incidence of major cardiovascular events over a 21-year median follow-up of participants in the DPP trial (Diabetes Prevention Program) and DPPOS (Diabetes Prevention Program Outcomes Study).

Methods:​

During DPP, 3234 participants with impaired glucose tolerance were randomly assigned to metformin 850 mg twice daily, intensive lifestyle or placebo, and followed for 3 years. During the next 18-year average follow-up in DPPOS, all participants were offered a less intensive group lifestyle intervention, and unmasked metformin was continued in the metformin group. The primary outcome was the first occurrence of nonfatal myocardial infarction, stroke, or cardiovascular death adjudicated by standard criteria. An extended cardiovascular outcome included the primary outcome or hospitalization for heart failure or unstable angina, coronary or peripheral revascularization, coronary heart disease diagnosed by angiography, or silent myocardial infarction by ECG. ECGs and cardiovascular risk factors were measured annually.

Results:​

Neither metformin nor lifestyle intervention reduced the primary outcome: metformin versus placebo hazard ratio 1.03 (95% CI, 0.78–1.37; P= 0.81) and lifestyle versus placebo hazard ratio 1.14 (95% CI, 0.87–1.50; P = 0.34). Risk factor adjustment did not change these results. No effect of either intervention was seen on the extended cardiovascular outcome.

Conclusions:​

Neither metformin nor lifestyle reduced major cardiovascular events in DPPOS over 21 years despite long-term prevention of diabetes. Provision of group lifestyle intervention to all, extensive out-of-study use of statin and antihypertensive agents, and reduction in the use of study metformin together with out-of-study metformin use over time may have diluted the effects of the interventions.

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.056756

My understanding is if you have type 2 diabetes and use metformin you have better longitivity, then someone who is not type 2 diabetic and does not use metformin.

 

[Biobro]

My understanding is if you have type 2 diabetes and use metformin you have better longitivity, then someone who is not type 2 diabetic and does not use metformin.

You probably mean this study. Yes if you already have type 2 diabetes,
But if you are high risk patient or non risk patient you get no longevity benefits.

Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls​

Conclusions: Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non-diabetic controls.

Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls - PubMed

Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non-diabetic controls. Those treated with sulphonylurea had markedly reduced survival compared with both matched controls and those receiving metformin monotherapy. This supports the position...

pubmed.ncbi.nlm.nih.gov

 

[Vince]

You probably mean this study. Yes if you already have type 2 diabetes,
But if you are high risk patient or non diabetic you get no longevity benefits.

Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls​

Conclusions: Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non-diabetic controls.

Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls - PubMed

Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non-diabetic controls. Those treated with sulphonylurea had markedly reduced survival compared with both matched controls and those receiving metformin monotherapy. This supports the position...

pubmed.ncbi.nlm.nih.gov

I think the main benefit for everyone should be diets that do not spike your insulate levels. Which is of course low carb.

I almost forgot to mention, diet soda will turn you into a type 2 diabetic.