Latest Update on Metformin

[Auggie68]

Will metformin cause muscle soreness?

 

[madhacker]

No wonder my IBS got better when I was on Metformin. I may try to start "Metformin Synergy" from Empower Pharmacy with Leucine and low dose sildenafil (yes, Viagra) to see if I do not lose muscle pump or get tired like I did with Metformin monotherapy 500 mg twice per day. I could use losing a few of my quarantine pounds also. These are not human studies but...

Anti-inflammatory mechanism of metformin and its effects in intestinal inflammation and colitis-associated colon cancer - PubMed

These results indicate that metformin suppresses NF-κB activation in intestinal epithelial cells and ameliorates murine colitis and colitis-associated tumorigenesis in mice, suggesting that metformin could be a potential therapeutic agent for the treatment of inflammatory bowel disease.

pubmed.ncbi.nlm.nih.gov

Metformin Ameliorates Inflammatory Bowel Disease by Suppression of the STAT3 Signaling Pathway and Regulation of the between Th17/Treg Balance

Objective Metformin is used to treat type 2 diabetes. We sought to determine whether metformin reduces inflammation, by regulating p-signal transducer and activator of transcription 3 (STAT3) expression and T-helper 17 (Th17) cell proliferation, in a mouse model of inflammatory bowel disease...

journals.plos.org

Hi Nelson,

I have tried this combination and found that I gained muscle and I believe your suspicions are correct, you will not lose your muscle pump or mass, as I did not. The muscle sensitizing effect on muscle seems to be profound in my case, subjectively speaking.

My pre-existing concerns of it's negative effects on attenuating the beneficial effects of exercise is still of concern.

Have you tried the combination of these three agents?

 

[madhacker]

Love Affair With Metformin: Still Strong, or Time to Move On?
.... "at $4 a month," it's hard to argue with the economics, she noted.

Newer drugs that have shown benefit in cardiovascular outcomes trials include the SGLT-2 inhibitors empagliflozin (Jardiance, Boehringer Ingelheim) in EMPA-REG OUTCOME and canagliflozin (Invokana, Johnson & Johnson) in CANVAS, and the GLP-1 agonists liraglutide (Victoza, Novo Nordisk) in LEADER and semaglutide (Ozempic, Novo Nordisk) in SUSTAIN-6.

But these studies were mainly conducted in patients with high-risk type 2 diabetes who had a long duration of disease and already had cardiovascular disease (CVD) or a number of risk factors for it.

"So these data do not directly translate to 87% of our population," requiring first-line therapy for type 2 diabetes, Aroda argued.

She also pointed to safety, acknowledging, "We all know the potential for gastrointestinal disturbances with metformin and B12 deficiency," but this pales in comparison to the numerous safety warnings issued for newer drugs over the past few years, she said."

..."metformin does not address many of the core pathophysiologies of type 2 diabetes, she argued, and secondly, "you do not improve metabolic parameters as well as other [drugs] can." Although metformin lowers HbA1c, it is fairly neutral when it comes to any benefits on weight, blood pressure, and lipids, for example."

Source

I'm a big fan of the evidence for semaglutide and have recently started taking it for personal researching. I may consider combining with canagliflozin once I get a feel for long-acting GLP-1. I will report back.

 

[Nelson Vergel]

Metformin and Its Benefits in Improving Gut Microbiota

I was wondering if anyone had any thoughts on research (animal studies mostly) demonstrating that metformin treatment could increase A. muciniphila gut population.... Lee H, Ko G. Effect of metformin on metabolic improvement and gut microbiota. Appl Environ Microbiol. 2014 Oct;80(19):5935-43...

www.excelmale.com

 

[Nelson Vergel]

Interesting new data on Metformin and immune function in HIV+ men with normal glucose and undetectable viral load at baseline. They may include Metformin in combination with cure-related therapies as we get more data.

AIDS Research and Human Retroviruses- Ahead of PrintFull Access
Effects of Brief Adjunctive Metformin Therapy in Virologically Suppressed HIV-Infected Adults on Polyfunctional HIV-Specific CD8 T Cell Responses to PD-L1 Blockade
Glen M. Chew,
Ana Joy P. Padua,
Dominic C. Chow,
Scott A. Souza,
Danielle M. Clements,
Michael J. Corley,
Alina P.S. Pang,
Marissa M. Alejandria,
Mariana Gerschenson,
Cecilia M. Shikuma, and
Lishomwa C. Ndhlovu
Published Online:5 Nov 2020my.access — University of Toronto Libraries Portal



Abstract
Targeting inhibitory immune checkpoint receptor pathways has shown remarkable success in improving anticancer T cell responses for the elimination of tumors. Such immunotherapeutic strategies are being pursued for HIV remission. Metformin has shown favorable clinical outcomes in enhancing the efficacy of programmed cell death-1 (PD-1) blockade and restoring antitumor T cell immunity. Furthermore, monocytes are known to be a strong predictor of progression-free survival in response to anti-PD-1 immunotherapy. In a single-arm clinical trial, we evaluated the immunological effects over an 8-week course of metformin therapy in seven euglycemic, virally suppressed HIV-infected participants on combination antiretroviral therapy (cART). We assessed changes in peripheral HIV-Gag-specific T cell responses to immune checkpoint blockade (ICB) with anti-PD-L1 and anti-T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) monoclonal antibodies (mAbs) and changes in CD8 T cell and monocyte subsets using flow cytometry. Study participants were all male, 71% (5/7) Caucasian, with a median age of 61 years, CD4 count of 739 cells/μL, and plasma HIV RNA of <50 copies/mL on stable cART for >1 year. Ex vivo polyfunctional HIV-Gag-specific CD8 T cell responses to anti-PD-L1 mAb significantly improved (p < .05) over the 8-week course of metformin therapy. Moreover, frequencies of both intermediate (CD14+CD16+; r = 0.89, p = .01) and nonclassical (CD14lowCD16+; r = 0.92, p = .01) monocytes at entry were predictive of the magnitude of the anti-HIV CD8 T cell responses to PD-L1 blockade. Collectively, these findings highlight that 8-week course of metformin increases the polyfunctionality of CD8 T cells and that baseline monocyte subset frequencies may be a potential determinant of PD-L1 blockade efficacy. These data provide valuable information for HIV remission trials that utilize ICB strategies to enhance anti-HIV CD8 T cell immunity.

More on Metformin and HIV:

Repurposing Metformin in Nondiabetic People With HIV: Influence on Weight and Gut Microbiota
Repurposing Metformin in Nondiabetic People With HIV: Influence on Weight and Gut Microbiota

 

[madhacker]

Metformin Synergy Capsules

Choose Empower Pharmacy for compounded Metformin Synergy Capsules. The leading accredited 503A and FDA-registered 503B compounding pharmacy.

www.empowerpharmacy.com

Metformin Weight Loss Combo: Effect of Leucine plus Metformin and Sildenafil Combination

Objective: Leucine was previously demonstrated to allosterically activate mammalian sirtuin 1 and synergize with other sirtuin 1/AMP-activated protein kinase/nitric oxide pathway activators to modulate energy metabolism. The objective of this study was to evaluate the effects of a triple...

www.excelmale.com

Hi Nelson,

Have you tried this combination yet? If so, did you experience a decrease in muscle pumps or experience any fatigue? Generally, what was your experience?

thanks for your response in advance!

 

[Nelson Vergel]

Effect of Metformin on Testosterone Levels in Male Patients With Type 2 Diabetes Mellitus Treated With Insulin - PMC

To explore the chronic effects of metformin on testosterone levels in men with type 2 diabetes mellitus (T2DM). This is a secondary analysis of a real-world study evaluating the efficacy and safety of premixed insulin treatment in patients with T2DM ...

www.ncbi.nlm.nih.gov

 

[madhacker]

@Nelson Vergel

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

OBJECTIVE. To determine whether metformin or lifestyle modification can lower rates of all-cause and cause-specific mortality in the Diabetes Prevention Pr

diabetesjournals.org

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

​

"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."​

 

[Nelson Vergel]

Thanks for sharing!

Let's see what this study shows:

TAME - Targeting Aging with Metformin - American Federation for Aging Research

The Targeting Aging with Metformin (TAME) Trial is a series of nationwide clinical trials to uncover what metformin means for older populations living longer and healthier lives.

www.afar.org

A new study explores anti-aging properties of metformin

Research has found that metformin targets the chemicals produced by age-related senescent cells—normal cells that stop dividing and produce toxic substances damaging to the cells around them, said James Kirkland, director of the Robert and Arlene Kogod Center on Aging at the Mayo Clinic in...

www.excelmale.com

 

[madhacker]

Thanks for sharing!

Let's see what this study shows:

TAME - Targeting Aging with Metformin - American Federation for Aging Research

The Targeting Aging with Metformin (TAME) Trial is a series of nationwide clinical trials to uncover what metformin means for older populations living longer and healthier lives.

www.afar.org

A new study explores anti-aging properties of metformin

Research has found that metformin targets the chemicals produced by age-related senescent cells—normal cells that stop dividing and produce toxic substances damaging to the cells around them, said James Kirkland, director of the Robert and Arlene Kogod Center on Aging at the Mayo Clinic in...

www.excelmale.com

I thought you would find that interesting.

In terms of awaiting further data and outcomes with TAME, I agree. I'm looking forward to reviewing data beyond what's easily measurable.

 

[Fernando Almaguer]

I thought you would find that interesting.

In terms of awaiting further data and outcomes with TAME, I agree. I'm looking forward to reviewing data beyond what's easily measurable.

There has been a study shown according to Dr. Stanfield (recent) that metformin does not decrease risk of heart disease or cancer. It does do a great job of preventing type 2 diabetes though!

 

[Fernando Almaguer]

 

[madhacker]

There has been a study shown according to Dr. Stanfield (recent) that metformin does not decrease risk of heart disease or cancer. It does do a great job of preventing type 2 diabetes though!

He's referring to the paper I posted above.

The authors of the paper state that their study was not fully controlled, we're still awaiting further research as Nelson mentioned.

 

[Fernando Almaguer]

He's referring to the paper I posted above.

The authors of the paper state that their study was not fully controlled, we're still awaiting further research as Nelson mentioned.

okay !

 

[nodoctor]

I'm off metformin mainly because my GI didn't tolerate it well. gas/shits. I also remember reading it reduces IGF considerably, and lastly I remember some problematic cancer stuff with long term. I actually do think it permanently improved my insulin sensitivity though--even after I stopped it.

 

[Fernando Almaguer]

I

I'm off metformin mainly because my GI didn't tolerate it well. gas/shits. I also remember reading it reduces IGF considerably, and lastly I remember some problematic cancer stuff with long term. I actually do think it permanently improved my insulin sensitivity though--even after I stopped it.

Sorry to hear you stopped. I actually welcome the GI disturbances as a sign the medication is working. If we eat clean it isn't so bad.

 

[Nelson Vergel]

Metformin and testosterone replacement therapy inversely associated with hormone-associated cancers (prostate, colorectal and male breast cancers) among older White and Black men - PubMed

Pre-diagnostic use of metformin and TTh were, independently and jointly, inversely associated with incident prostate and colorectal cancers. The risk of HRCs was also reduced among White, Black and Other Race men. Greatest reduced associations of prostate and colorectal cancers and HRCs were...

pubmed.ncbi.nlm.nih.gov

 

[Nelson Vergel]

Effects of short term metformin administration on androgens in normal men

Nadima S Shegem 1, Abeer M Nasir, Abdel-Kareem Jbour, Anwar M Batieha, Moh'd S El-Khateeb, Kamel M Ajlouni

Abstract
Objective: To study the effect of metformin on androgens in normal men.

Methods: A total of 12 healthy males volunteered to participate in the study. A blood sample was obtained from each of them and analyzed for the following: Testosterone (total and free), sex hormone binding globulin dehydroepiandrosterone sulphate, 17-hydroxyprogesterone, luteinizing hormone, and follicle stimulating hormone. In addition, each participant was subjected to a glucose tolerance test and his insulin level was measured. Metformin 850 mg twice daily for 2-weeks was given to each subject after which the above tests were repeated. A paired t-test was used to assess the statistical significance of any observed differences before and after metformin.

Results: After metformin administration, there was a significant reduction in serum level of total testosterone (p=0.0001), free testosterone (P=0.002), and 17 hydroxyprogesterone (p=0.0001). There was also a significant increase in serum level of sex hormone binding globulin (p=0.009) and dehydroepiandrosterone sulphate (P=0.0008). Serum levels of luteinizing hormone and follicle stimulating hormone showed no significant changes. Similarly, there were no changes in fasting plasma glucose, fasting serum insulin, weight, or blood pressure.

Conclusion: Metformin administration was associated with a reduction in total testosterone, free testosterone, and 17-hydroxyprogesterone and an increase in sex hormone binding globulin and dehydroepiandrosterone sulphate in normal males. The clinical significance of these findings needs further investigation.

Saudi Med J . 2002 Aug;23(8):934-7.

 

[Deleted member 43589]

Metformin gives my wife horrible stomach cramps and diarrhea.

Not sure what kind she is taking but Metformin oral tablet comes in two forms: immediate-release and extended-release. Guys I know who have had stomach cramps etc say the extended release did not cause this. It might be for some the short release is much worse because of the speed it releases. I don't believe science has determined why Metformin causes gastrointestinal distress but there are different hypothesis proposed, including stimulation of intestinal secretion of serotonin, alteration in incretin and metabolism of glucose, and malabsorption of bile salts.

Some studies have shown taking metformin tablets at mealtimes, or using careful dose adjustment to minimize poor compliance with immediate release form of metformin or switching to extended release form of metformin can reduce GI symptoms. Another study show switching to capsules helped.

Long-Term Metformin Use Linked with Vitamin B12 Deficiency​

https://www.endocrineweb.com/news/diabetes/20265-long-term-metformin-use-linked-vitamin-b12-deficiency

 

[captain]

Metformin identified as a potential atrial fibrillation treatment in collaborative research​

Metformin identified as a potential atrial fibrillation treatment in collaborative research