Latest Update on Metformin


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Maybe metformin dropped B12 which is what caused the rise in homocysteine. Metformin is known to cause a drop in B vitamins.
That was certainly my experience. After a couple of years on Metformin I noticed that a consistent decline in my serum B-12 levels had taken me well below the bottom of the reference range, which I attributed to the Metformin. Started on a 500 mcg/day oral B-12 supplement, and after a few months my B-12 level has risen back into the reference range.
Guys, taking 500mg/x2/day of Metformin, is it possible to have any issues if you drop carbs pretty low in your diet?
I'm on 500mgx2 (3 months) and also eat ZeroCarb Carnivore (8 months). No issues for me. I wake up with 90-105 blood sugar and it drops to 75-90 late at night. A1C before Metformin was 5.0.
I've heard of 250 twice per day all the way up to 1000 twice per day.
From what I've seen depends on the prescriber.
Nelson has posted a ton of good info on Metformin here on this site though.
And I believe he did an entire podcast with Jay Campbell on the subject.

Nelson Vergel

Oh oh

Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults

Metformin and exercise independently improve insulin sensitivity and decrease the risk of diabetes. Metformin was also recently proposed as a potential therapy to slow aging. However, recent evidence indicates that adding metformin to exercise antagonizes the exercise‐induced improvement in insulin sensitivity and cardiorespiratory fitness. The purpose of this study was to test the hypothesis that metformin diminishes the improvement in insulin sensitivity and cardiorespiratory fitness after aerobic exercise training (AET) by inhibiting skeletal muscle mitochondrial respiration and protein synthesis in older adults (62 ± 1 years). In a double‐blinded fashion, participants were randomized to placebo (n = 26) or metformin (n = 27) treatment during 12 weeks of AET. Independent of treatment, AET decreased fat mass, HbA1c, fasting plasma insulin, 24‐hr ambulant mean glucose, and glycemic variability. However, metformin attenuated the increase in whole‐body insulin sensitivity and VO2max after AET. In the metformin group, there was no overall change in whole‐body insulin sensitivity after AET due to positive and negative responders. Metformin also abrogated the exercise‐mediated increase in skeletal muscle mitochondrial respiration. The change in whole‐body insulin sensitivity was correlated to the change in mitochondrial respiration. Mitochondrial protein synthesis rates assessed during AET were not different between treatments. The influence of metformin on AET‐induced improvements in physiological function was highly variable and associated with the effect of metformin on the mitochondria. These data suggest that prior to prescribing metformin to slow aging, additional studies are needed to understand the mechanisms that elicit positive and negative responses to metformin with and without exercise.

low dose (1.1 g leucine/0.5 g metformin/0.5 mg sildenafil), or high dose (1.1 g leucine/0.5 g metformin/1.0 mg sildenafil) twice daily.
To measure this you need a scale measuring mg. How can one cut 1 mg of sildenafil?

Nelson Vergel

Metformin Decreased the Risk of Dementia

Black individuals who develop type 2 diabetes are more likely than their white counterparts to develop dementia. Now, findings from a new study point to a possible preventive strategy: Putting older patients on metformin when they are diagnosed could reduce their risk for dementia by as much as 40%, whereas sulfonylureas do not seem to have such an effect.

The researchers did not examine cause and effect, so their findings are not conclusive, and very few women were included in the study. Still, the authors said that their data showing a 29% lower risk of dementia associated with metformin use in black patients aged 65-74 years, and a 40% lower risk in those aged 50-64 years, suggested that “this inexpensive, widely available treatment could be broadly prescribed to substantially reduce the risk of dementia in younger [black] patients with [type 2 diabetes]” (Ann Fam Med. 2019;17:352-62).

Nelson Vergel

Weight Loss With Metformin Maintained at 15 Years

Although the benefits of metformin on blood glucose and insulin sensitivity are known, the benefits of metformin on weight loss are not quite as well understood, Gadde's group explained.

"Metformin is not known to significantly alter energy expenditure," they wrote, adding that some studies have shown decreases in appetite and food intake with metformin. "It is well recognized that the human body adapts to weight loss with compensatory neuronal, hormonal, and metabolic changes that promote weight regain. Whether metformin counters some of these compensatory changes must be further investigated."

Nelson Vergel

Clin Pharmacol. 2019 Aug 6. doi: 10.1002/jcph.1507. [Epub ahead of print]

The Impact of Testosterone on Metformin Action on Hypothalamic-Pituitary-Thyroid Axis Activity in Men: A Pilot Study.
Krysiak R1, Szkróbka W1, Okopień B1.


The effect of metformin on thyrotrope function seems to be sex dependent. The aim of this study was to determine the role of endogenous testosterone in the impact of metformin on hypothalamic-pituitary-thyroid axis activity. The study population consisted of 2 groups of men with nonautoimmune hypothyroidism matched for age, weight, insulin sensitivity, and thyrotropin levels. The first group (n = 11) included subjects with low serum testosterone levels, while the second (n = 12) men with testosterone levels within the reference range. Because of concomitant type 2 diabetes, all men were treated with metformin (2550-3000 mg daily). Circulating levels of glucose, prolactin, testosterone, gonadotropins, thyrotropin, and free thyroid hormones were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at baseline and 16 weeks later. In both study groups, metformin decreased plasma glucose levels and improved insulin sensitivity. However, only in men with low testosterone levels, the drug decreased thyrotropin levels, reduced Jostel's thyrotropin index, and increased SPINA-GT. Metformin-induced changes in thyrotropin and Jostel's index correlated with their baseline values, baseline levels of testosterone, and with the effect of treatment on insulin sensitivity. In men with neither low or normal testosterone levels, metformin affected free thyroid hormones, prolactin, testosterone, gonadotropins, and SPINA-GD. The obtained results suggest that the impact of metformin on thyrotrope function depends on the androgen status of a patient.