Latest Update on Metformin

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madhacker

Member
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...




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

Member
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

Founder, ExcelMale.com
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

Member


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!
 

madhacker

Member
@Nelson Vergel

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

Founder, ExcelMale.com
Thanks for sharing!

Let's see what this study shows:


 

madhacker

Member
Thanks for sharing!

Let's see what this study shows:


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

Well-Known Member
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!
 

madhacker

Member
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.
 

nodoctor

Active Member
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

Well-Known Member
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

Founder, ExcelMale.com
 

Nelson Vergel

Founder, ExcelMale.com
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.
 

BigTex

Well-Known Member
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​

 
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