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Should you take metformin to slow aging? Longevity Supplements.

Oliver Zolman MD

· Longevity

Medical Disclaimer: Services and guides do not provide medical advice. Do not make any changes to your health behaviours based on this article without consulting your licensed clinicians first. See our medical disclaimer.

In summary: it is unclear that in healthy people, with no "pre-diabetes" (where your blood sugar is not optimal, but not so high it is classed as "full diabetes"), and who already lead a very healthy lifestyle and are not overweight, that metformin could have any additional benefit.

However for people that are unable to lead a healthy lifestyle, such as due to other medical conditions, or simply finding developing such habits too challenging, metformin could have a role in select areas such as:

  • preventing certain types of cancer (such as bowel cancer for people at high risk), even if they do not have prediabetes or diabetes
  • preventing type 2 diabetes if you have type 2 pre-diabetes
  • preventing the risk of infections in those with lung failure (chronic obstructive pulmonary disease - COPD) even if they do not have prediabetes or diabetes
  • reducing advanced-glycation-end-products (AGEs - clumps of proteins and sugars that accumulate in the body with age) in those that have high risk of accumulating AGEs

Metformin has a considerable number of side effects and risks that need to be managed too, for example

  • A 50% risk of ongoing diarrheoa, flatulence, anal leakage or nausea; this may be helped through taking slow release form of metformin - which may be around 2 - 4 times more expensive, slowly building up the dose, using certain types of probiotics, timing to only take metformin shortly after a large meal, and stopping and starting 
  • A 10% risk of vitamin B12 deficiency, or a much higher risk of B12 deficiency if your blood levels of total B12 are already near the bottom of the normal range; this can likely be prevented by taking a correct dose and form of vitamin B12 orally 
  • A risk of life threatening "lactic acidosis" if your kidneys are damaged and metformin is unable to be excreted from the body; this risk is likely increased if you don't tell your doctors that you are taking metformin, or if you do not do, typically, annual blood tests to measure kidney function

Whilst UK clinical guidelines do permit prescriptions of metformin for preventing diabetes if you have pre-diabetes and lifestyle interventions are not working for you

It is important to note that metformin may not have as good an effect on type 1 pre-diabetes or late-onset autoimmune diabetes of adults (LADA) pre-diabetes. The high blood sugars in these conditions are due to autoimmune processes that destroy pancreas cells meaning you can't produce enough of a hormone called insulin which moves blood sugar into the cells, and metformin does not help one produce more insulin.
What exactly do we mean by aging?

Aging occurs when any of 9 categories of molecular damage occur and are not repaired. The details about these 9 categories of damage can be found here. Scientifically minded readers may also be interested in the original scientific paper in PubMed regards these 9 'Hallmarks of Aging' found here. These 9 categories have many different subcategories.

These 9 categories of damage then have consequences and can present themselves as many hundreds of "age-related diseases", especially after age 70 when this damage starts building up at a faster rate than at earlier ages.

These age-related diseases include things like osteoarthritis, cancer, dementias like Alzheimer's, and blood vessels getting damaged like in strokes (such as blood vessels bursting), plaques in the arteries, or aneurysms (swelling up and ballooning out of arteries).

How does metformin relate to aging?

Metformin is a diabetes drugs that has been used for over 50 years around the world. Diabetes is a condition where your body cannot control its level of blood sugar properly. High quality clinical trials have proven that metformin can lower blood sugar in people with diabetes.

Other experiments are starting to show that metformin may tackle certain other aspects of the 9 categories of aging damage and in people without diabetes. This is why we created this guide to see which people without diabetes might benefit from taking metformin.

How does diabetes relate to aging?

When your blood sugar level is high this causes aging damage. For example, the sugar molecules can stick to other molecules that make them not work properly (for example, collagen, elastin, immune cells and cancer cells).

As a result, having diabetes or prediabetes (discussed below) can accelerate the accumulation of aging damage and can make you experience aging diseases like those mentioned above sooner and to a worse extent.

What is diabetes exactly?

Diabetes is diagnosed when your blood sugar level is above a certain level on 2 occasions. Doctors and scientists decided this level by looking tracking the health and symptoms and other medical information of people with different blood sugar levels for many years, and seeing which people get sick.

There are 3 types of diabetes that are related to blood sugar: Type 1 diabetes mellitus, type 2 diabetes mellitus and "LADA" (known as late onset autoimmune diabetes in adults). LADA can be thought of as "type 1.5 diabetes" as it contains elements of both type 1 diabetes (autoimmunity damaging your pancreas) and type 2 diabetes (lack of responding to the hormone that controls blood sugar level.

What is pre-diabetes?

Pre-diabetes is when your blood sugar levels are not ideal, but they are not so abnormal that would be classified as full diabetes. It is an "intermediate zone" between optimal glucose (sugar) levels, and dangerously high glucose levels as with diabetes.

People with prediabetes are at high risk of their blood sugars getting worse, and becoming classified as full diabetes, according to studies tracking people with prediabetes.

Prediabetes can apply to type 1, LADA and type 2 diabetes alike (the prediabetes may be caused by the unique biological processes that cause the full versions of these three types of diabetes).

How is diabetes diagnosed?

After age 30, of all diabetes diagnoses about 85% is type 2 diabetes, about 5% type 1 diabetes and about 10% LADA.

For all of these types of diabetes blood sugar tests are used to diagnose them. Then if the blood sugar is high, more tests may be done to see whether it is type 1, 1.5 or 2 diabetes if it is not clear.

2 measurements, on separate days, of the following means you have one of these diabetes conditions:

A) Fasting blood glucose above 7 mmol/L (no food or drink other than water for 8 hours) (reference)

B) Blood glucose levels above 11 mmol/L 2 hours after drinking 75g of dextrose sugar and nothing else (reference)

C) Blood glucose levels ever above 11 mmol/L at any time after eating any combination of foods, or any time of day (reference)

D) Your red blood cells have more than 48 glucose molecules on them for each haemogloblin molecule, i.e. more than 48 mmol/mol. (reference)

E) Your red blood cells glucose molecules can also be measured the old way by counting percentage of red blood cell haemoglobin molecules that have sugar on them, if it is above 6.5% this is classed as diabetes - but it is better to use method C. (reference)

For Options D & E, this is known as a HbA1c test (Hb stands for haemoglobin).

HbA1c tests (methods D & E) provide an estimate of your average blood sugar levels over the past 3 months, as this is how long red blood cells last for in the body before being replaced). Methods A, B and C are thought to provide a measure of your average blood sugar levels over a shorter time than 3 months.

"mol" is a chemistry term and refers to "1 mole" (wikipedia page) which means 600 septillion (a very large number). Its just a way of simplifying large numbers to easy ones.

New ways of diagnosing diabetes?

Novel ways of checking for diabetes include using a new method called "interstitial glucose", however this method is still being developed as a diagnostic. This method typically measures the glucose levels every 15 minutes in the space around your lower skin cells and fat cells, not in your blood stream. This is done by wearing a patch with a small plastic rod that sticks into the skin. The patch is worn for 2 weeks normally before stopping or being replaced.

There are a few ways diabetes can be measured with interstitial glucose tests. Diabetes can be considered if on 2 separate days:

F) Average 24 hour interstitial glucose is above 7 mmol/L (125 mg/dL for USA units) (95% of a healthy population will have levels below this).

G) Interstitial glucose ever goes above 11 mmol/L (200 mg/dL for USA units)

The device used to measure the patch is called "Freestyle Libre", and costs around £50 for 2 patches and £100 for the scanner that scans the patch to gather the information, however if you have a newer phone you can download an app that acts as the scanner, meaning you don't have to buy the scanner and can save that £100.

If you are considering using a freestyle libre (interstitial glucose monitor) it is best to discuss with a doctor familiar with these devices, or one that is willing to learn about how to advise patients using such a device.

We're going to cover the following questions now in more detail

1. Is the study where metformin users with diabetes survived longer than non-metformin users without diabetes legit?

2. Is there any good evidence of metformin providing age-related disease benefits for those without prediabetes or diabetes?

3. What about vitamin B12 side effects from metformin?

4. Should I take metformin if I don't have prediabetes?

5. Should I take metformin if I have diabetes or prediabetes?

6. How do I make a decision and which clinicians should I discuss it with?

7. References and systematic review search strategy

1. Is the study where metformin users with diabetes survived longer than non-metformin users without diabetes legit?

A meta analysis (MA) of observational studies claimed that metformin users may have greater survival than non metformin users; however it was not clear that they adjusted for all confounding factors so the study results can be considered to be invalid or majorly flawed (source).

2. Is there any good evidence of metformin providing age-related disease benefits for those without prediabetes or diabetes?

Colon Cancer and pre-cancer

  • "The authors conducted a multicenter, double-blind, placebo-controlled randomized study (RCT) on 151 patients (79 in the metformin group, 72 in the placebo group) who had colorectal adenoma resected. Followup colonoscopy was performed after a year of treatment with low dose metformin (250mg/day). A significantly lower prevalence of polyps as well as adenomas was observed in the metformin group (total polyp prevalence 38%, 95% CI 26.7-49.3, in the metformin group vs. 56.5%, 95% CI 44.1-68.8, in the placebo group, p=0.034; adenoma prevalence 30.6%, 95% CI 19.9-41.2, in the metformin group vs. 51.6%, 95% CI 39.2-64.1, in the placebo group, p=0.016). The safety of low dose metformin treatment was confirmed, with 11% of patients having mild adverse effects, most commonly constipation (4.5%) and diarrhea (3.8%) [85]." (Source)
  • Mouse and cell evidence shows promising results for metformin in addition to normal chemo for colon cancer (source)

Advanced glycation end products (AGEs)

"Metformin may have an effect independent of blood sugar control at protecting against advanced glycation end product formation"

  • “Independent of its anti‐hyperglycaemic and insulin sensitizing actions, metformin moderates AGE accumulation by directly sequestering dicarbonyl compounds.” (source)
  • It is unclear if this is only in significant in diabetics or of clinical significance 
  • One proposed mechanism of action: “Apart from the effects on the glycaemic profile, metformin appears to improve scar formation by targeting skin fibroblasts.84 It has an inhibitory effect on AGEs-induced apoptosis in human dermal fibroblasts by regulating the expressions of caspase-3, Bax and Bcl-2." (source)

Gum aging

Topical ~1% metformin may reduce gum probing depth and gum clinical attachment loss

Topical 10 mg /kg metformin gel may improve scaling and planing outcomes and periodontitis treatment

Inflammation

Metformin may reduce CRP by 0.2 mg/L (but this is likely clinically insignificant) according to a MA (source)

Vaccine response in non-diabetics non-prediabetics - ongoing clinical trial

Metformin is being tested in clinical trials to see whether it can enhance the vaccine response (flu vaccine) in non-prediabetics and non-diabetics; with a dose of 1.5 g a day XR metformin for 12 weeks prior to flu vaccine (source). Similarly in pneumococcal 13 type vaccine (source).

COPD in non-diabetics - ongoing clinical trial

Metformin to lower airway secretion glucose in non-diabetics with COPD to prevent unwanted bacterial and other microbial growth that leads to infections (source)

Cancer in non-diabetics - ongoing clinical trials

Metformin is being used to treat LKB-1 inactive lung adenocarcinoma in non-type1/2 diabetics and with BMI under 20 (source)

Metformin is being used to treat potentially malignant oral lesions diagnosed via histology in non-type1/2 diabetics (source)

Metformin is being tested to see if it can reduce tumour ki-67 expression after hysterectomy in endometrial cancer (source)

Metformin is being used in preventing head and neck cancer progression (source)

3. What about vitamin B12 side effects from metformin?

Metformin may lower B12 levels by 80 pmol/L within 6 weeks (1.5 months), those within 100 pmol/L of the lower limit of normal total B12 should supplement B12 to prevent moving to the deficiency range (source); however metformin was not associated with an increase in total homocysteine, a surrogate marker of various B vitamin function (source).

Taking 125 micrograms methylcobalamin a day or 1000 micrograms a week (which can be part of a b complex pill) should prevent B12 deficiency from metformin, and in general. Methylcobalamin is better used by the body than cyanocobalamin for most people. Pills are just as effective as B12 injections so there is no need to undergo logistically more burdonesome and painful and riskier injections every month (unless as medically indicated such as unable to absorb by the gut or in severe B12 deficiency cases etc.)

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Should I take metformin even if I don't have prediabetes?

Metformin may be useful if you have pre-type 2 diabetes to prevent conversion to full type 2 diabetes. However, it may not add any benefit regards optimal diet and exercise. It could be hypothesised that if someone is facing difficulty in adopting diet and exercise changes (especially if they are ill or illness makes diet and exercise changes difficult for some reason), then metformin might be useful. Likewise it is unclear metformin provides any added benefit for weight loss above diet and exercise, and is likely worse than other pharmaceutical interventions for weight loss (see next bullet points, analysing data for this source)

  • From this 2018 systematic review on metformin for weight loss I first skipped through all the child studies and focused on adult population only. I then skipped through all the shorter term trials, going to the category of adult trials with the longest follow up (as this is the best data) - this is the 18+ month follow up minimum adult trial category at the bottom of page 15
  • Reference 21 analysis: In those with any type of pre-diabetes, age over 25 and BMI over 24, LIFESTYLE INTERVENTIONS alone lost 5.6 kg at 2.8 years average follow up compared to only 2.1 kg with metformin and 0.1 kg with no intervention (p = 0.01... which is a good p value.). There was ALSO over a 95% chance that lifestyle interventions alone outperform metformin for preventing diabetes in this population with unspecified pre-diabetes. This is consistent with other meta analyses. 
  • Reference 22 analysis: Even after 10 years follow up of this first double blind RCT (reference 21) the weight loss in lifestyle interventions alone was still greater than in metformin alone
  • Reference 26 shows no statistically significant difference between lifestyle and metformin
  • Reference 24's slight outperformance of metformin over lifestyle alone can be argued to be insignfiicant due to p of 0.04 being too high a threshold due to many p values reported in the paper (statistical multiplicity)
  • Reference 47 is not relevant as there was no active comparison group
  • In terms of other drugs or interventions for weight loss, from my knowledge orlistat or extra virgin olive oil have better evidence for adding additional benefit to lifestyle, and likely with fewer side effects. However, it is clear that lifestyle interventions alone can resolve the majority of obesity or high body fat % in most cases in theory, unlike metformin, orlistat or extra virgin olive oil.

Its also unclear if metformin will work for pre-type 1 diabetes or pre-late onset diabetes of adults (pre-LADA). But, if you don't have prediabetes the benefits may be limited to those discussed above regards preventing colon cancer and (not including its use in polycystic ovarian disease (PCOD) and gum conditions).

Metformin could be considered a "hedge" against times when your diet and exercise regimen is not optimal, such as undertaking behaviours that increase the risk of polyps or advanced-glycation end products. If you are on metformin whilst undertaking these behaviours then you may be protected against some of the damage they cause.

The following strategies can be taken to reduce the side effects of metformin that make it easier to justify its use in prediabetes, preventing advanced glycation end product accumulation and colon cancer prevention

  • Skipping straight to slow release metformin rather than trying instant release metformin
  • Starting at a very low dose of e.g. 250 mg straight after a meal and building up the dose very slowly, e.g. 125 mg per 2 weeks 
  • Peppermint tea may reduce nausea and vomiting side effect severity in first few months (according to patient reports)

  • If have severe gastro intestinal side effects that cause you to stop it, you can stop it and restart it from the lowest dose, slowly building up and you may be more tolerant the second time round (source of ongoing clinical trial for this)

  • Psyllium husk powder to reduce diarrheoa with metformin in T2DM patients (source of ongoing clinical trial for this)

  • Probiotics to prevent and treat gastrointestinal side effects of metformin: A multi-strain probiotic is being tested for this, containing: Sanprobi Barrier (Bifidobacterium lactis W52, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus lactis W19, Lactobacillus lactis W58, Lactobacillus acidophilus W37, Bifidobacterium bifidum W23, Lactobacillus salivarius W24) (source of ongoing clinical trial for this)

  • Separate doses by at least 6 hours to reduce gastrointestinal side effects

  • Ensuring your kidney function is over 30 mL/min glomerular filtration rate, or as advised by your doctor 
  • Taking 125 micrograms methylcobalamin a day or 1000 micrograms a week (which can be part of a b complex pill) should prevent B12 deficiency from metformin, and in general. Methylcobalamin is better used by the body than cyanocobalamin for most people. Pills are just as effective as B12 injections so there is no need to undergo logistically more burdonesome and painful and riskier injections every month (unless as medically indicated such as unable to absorb by the gut or in severe B12 deficiency cases etc.)

  • Metformin may prevent exercise induced mitogenesis which could be bad, so may be best to take metformin on days when not doing main exercise of the week.

  • Adjusting for age-related reductions in metformin metabolism independent of kidney function, e.g. halving the dose if over age 80.

  • Ensuring you tell your doctors that you are taking metformin, especially if you are ordering it off the internet without  a prescription, or privately and your public insurance doctors don't know about it
  • Stopping metformin in emergency medical situations and at least 2 days before having contrast imaging 
  • Considering not taking metformin if you have chronic or acute lactic acidosis or diabetic ketoacidosis
  • Discontinuing metformin when experiencing diarrheoa or vomiting resulting in further diarrehoa, vomiting and dehydration
  • Building it into your daily pill routine so it does not impact on quality of life of having to remember another pill (although this can be hard as it may provide the least side effects when taken after meals which is a different time to most other pills being taken)
  • Need annual monitoring of creatinine (£5 typically + cost of taking blood)

  • Annual monitoring of full blood count to look for anaemia (£5 typically + cost of taking blood)

  • 4 to 12 monthly monitoring total B12 test if history of low B12 or history of near low B12 (under 400 pmol/L) or if have not tested B12 in past year, or if vegetarian or vegan (£10 + cost of taking blood)

  • May have increased risk of side effects if have not taken a dose for 24 hours, so regular dosing may help

  • Occasionally, the inactive ingredients of metformin hydrochloride extended-release tablets may be eliminated as a soft mass in your stool that may look like the original tablet; this is not harmful and will not affect the way metformin hydrochloride extended-release tablets work to control your diabetes

  • Not drinking alcohol in access when taking metformin e.g. over 10 units, as increases risk of lactic acidosis - especially in those with impaired kidney function already (e.g. any glomerular filtration rate under 60 ml/min)

  • Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use, but could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol. Elderly, debilitated, or malnourished patients, and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects. Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking beta-adrenergic blocking drugs.

  • Metformin instant release scored only 3.7/5 from 938 patient user reviews at iodine.com, mostly due to diarrheoa, nausea, flatulence and bloating side effects

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% chance of side effects with metformin instant release versus slow release:

Up to 42% chance of significant or ongoing diarrheoa with instant release

Up to 7% chance of diarrheoa with Metformin Slow Release

Up to 18% chance of nausea/vomiting with instant release

5% with metformin slow release

With instant release: 9% chance of asymptomatic subnormal B12 levels

7% chance of flatulence

4% muscle weakness

3% indigestion

3% loss of appetite

3% abdominal bloating

2.5% abdominal discomfort

  • Knowing the following symptoms that may be because of lactic acidosis (metformin overdose)

    • you feel dizzy or lightheaded

    • you have a slow or irregular heartbeat

    • you feel very weak or tired

    • you have unusual (not normal) muscle pain

    • you have trouble breathing

    • you feel sleepy or drowsy

    • you have stomach pains, nausea or vomiting • you feel cold in your hands or feet

5. Should I take metformin if I have prediabetes or diabetes?

First, it is relevant to know whether your diabetes is in fact type 1, type 2 or "LADA" diabetes (Bronze Diabetes can also occur in those with haemochromotosis). Rather than having the most common type of diabetes or prediabetes (type 2 diabetes), you may have pre-type 1 diabetes or full type 1 diabetes or pre-late onset diabetes of adults (LADA) or full-LADA. Your GP may have also misdiagnosed it as type 2. The exact diagnosis changes the relevance of metformin as it is most likely to be useful in type 2 diabetes and type 2 prediabetes; and if it is used in combination with insulin for type 1 diabetes or LADA, metformin side effects such as hypoglycaemia may be more likely so it may carry higher risk.

Diagnostic criteria for prediabetes

ADA Criteria 2010:

Prediabetes: HbA1c 5.7–6.4%, or FBG 5.6-6.9 mmol/L, or 2hPG 7.8-11.0 mmol/L.

Diabetes: HbA1c > 6.5% or FBG > 7.0 mmol/L, or 2hPG > 11.1 mmol/L

but most of the studies that showed benefit for metformin and lifestyle used ADA 2003 or WHO 1999 criteria which are less strict than ADA 2010 criteira:

normal: FBG <110 mg/dL and OGTT <140 mg/dL;

IGT: OGTT 140 mg/dL-200 mg/dL,

IFG: FBG 100-124 mg/dL.

Is it type 1, type 2 or LADA diabetes?

Of diabetes cases diagnosed after age 30, 3% (assuming 10% of all diabetes mellitus is type 1) is type 1 diabetes, 2% to 12% is LADA type 1.5 diabetes , and 85% or more is type 2. (source). It could be important to differentiate between which of these one has as different interventions and strategies may be more effective for each (source 1, source 2). These can exist as pre-diabetic forms and so may have differing strategies to prevent them to progressing to full diabetes.

Metformin may have a place in type 1 diabetes (and hence LADA) too, according to observational, and RCTs not looking at clinical outcomes, particularly for more insulin insensitive and overweight or obese individuals (SR of RCTs, 2010; Literature review, 2018, MA 2018). This is relevant for more people than one might think given that 50% of contemporary type 1 diabetes cohorts are either overweight or obese. (LR, 2013)

In the cases of LADA and T1DM different management strategies may be needed to optimally manage such conditions. In the case of pre-type 1 diabetes or pre-LADA, if one chooses to test for such conditions whilst in the prediabetic state, different prevent strategies may be ideal to prevent progression to full type 1 diabetes or full LADA. In either case, whilst a GP may be able to perform C-peptide and GAD antibodies, in the case of any abnormal results referral to an endocrinologist specialising in diabetes should be taken at this point to manage the next steps. (Source: Author’s opinion)

(Fig 2 source)

Can metformin prevent diabetes in people who at high risk of developing diabetes?

  • "We identified four RCTs of metformin (25, 30, 37, 53). During the active intervention period [mean (SD), 1.93 (0.95) years; range, 1.0 to 3.2 years], the risk of BcT2DM was reduced by an RR (95% CI) of 0.71 (0.63, 0.80), with an I 2 of 0%. Estimated NNT (95% CI) was 23 (18, 33) for low-risk patients, 14 (11, 20) for average risk patients, and 10 (8, 14) for high-risk patients" (source)
  • This finding was strengthened by positive trial sequential analysis results (source)

What is the chance of developing full diabetes for those with pre-diabetes?

  • "The medium risk category was based on observational data showing that the incidence of DM in patients with impaired fasting glucose or impaired fasting tolerance was 25% for 3 to 5 years (9). Two other categories (10% higher and 10% lower than the 25%) were also used" (source)

What are the links to the trials that showed metformin prevented those already at high risk of type 2 diabetes, progressing to type 2 diabetes (i.e. being classified as type 2 diabetes based on different types of blood sugar tests)?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033082/

Can lifestyle modifications alone replace the need for metformin for preventing type 2 diabetes in those that are high risk for it?

  • There was no statistically significant difference between lifestyle and metformin; however, there is around a 50% chance that lifestyle changes could prevent diabetes conversion more strongly than metformin.

Is taking metformin AND doing lifestyle interventions better than just lifestyle alone for preventing type 2 diabetes in those that are high risk for it?

  • There was no difference to the reduction in risk of developing type 2 diabetes in those that added metformin to lifestyle interventions

It seems clear that metformin for full type 2 diabetes is beneficial

Taking into account alternative options to metformin for preventing type 2 diabetes in those that have pre-type 2 diabetes

Calorie restriction or reduction and mTOR boosting amino acid reduction (author's opinion)

Lifestyle changes

  • 50% chance were better at preventing conversion to type 2 diabetes from prediabetes based on RCTs than metformin alone (source)
  • This finding was strengthened by positive trial sequential analysis results (source)

Orlistat

  • Outperformed metformin for preventing conversion to type 2 diabetes from prediabetes in RCTs (source)
  • But this was in severely obese people BMI 39 only(source)

Reducing statins

  • A trial sequential analysis within a network meta-analysis of RCTs found a 20% increased relative risk of converting from prediabetes to type 2 diabetes from standard dose statin use

Acarbose

  • Not statistically significantly different from metformin for preventing conversion of pre diabetes to type 2 diabetes (source)

Thiazolidinedione

  • Outperformed metformin for preventing conversion to type 2 diabetes from prediabetes in RCTs (source)

GLP 1 receptor antagonists

  • Outperformed metformin for preventing conversion to type 2 diabetes from prediabetes in RCTs (source). But this was in severely obese people BMI 37 only (source)

6. How do I make a decision and which clinicians should I discuss it with?

1) Read through this article carefully

3) Download the Metformin London Health Manager off label prescribing informed consent form

Download by clicking here

3) Take this form to your doctor, either on your ipad, or emailing it to them, or printing it out

4) Ask your family doctor or an endocrinologist specialising in diabetes or a longevity focused medical doctor for their opinion on the risk-benefit in your situation

5) If you decide to go ahead with the prescription, keep a copy of this form, remember to tell all your clinicians that you take metformin and that it is in all your electronic health records, as the drug has to be stopped in certain situations or it can cause serious damage (via a condition known as lactic acidosis)

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7. References and systematic review strategy

Searches:

systematic[sb] AND (metformin NOT gestational NOT polycystic ovary syndrome NOT dialysis )

((((systematic review[ti] OR systematic literature review[ti] OR systematic scoping review[ti] OR systematic narrative review[ti] OR systematic qualitative review[ti] OR systematic evidence review[ti] OR systematic quantitative review[ti] OR systematic meta-review[ti] OR systematic critical review[ti] OR systematic mixed studies review[ti] OR systematic mapping review[ti] OR systematic cochrane review[ti] OR systematic search and review[ti] OR systematic integrative review[ti]) NOT comment[pt] NOT (protocol[ti] OR protocols[ti])) NOT MEDLINE [subset]) OR (Cochrane Database Syst Rev[ta] AND review[pt]) OR systematic review[pt])AND (("metformin"[MeSH Terms] OR "metformin"[All Fields]) NOT gestational[All Fields] NOT ("polycystic ovary syndrome"[MeSH Terms] OR ("polycystic"[All Fields] AND "ovary"[All Fields] AND "syndrome"[All Fields]) OR "polycystic ovary syndrome"[All Fields]) NOT ("renal dialysis"[MeSH Terms] OR ("renal"[All Fields] AND "dialysis"[All Fields]) OR "renal dialysis"[All Fields] OR "dialysis"[All Fields] OR "dialysis"[MeSH Terms]))

  • 328 articles identified, unrecorded subset retrieved for abstract, further subset retrieved for full text

Clinicaltrials.gov https://clinicaltrials.gov/ct2/results?cond=metformin&term=&type=&rslt=&age_v=&age=1&gndr=&intr=&titles=&outc=&spons=&lead=&id=&cntry=&state=&city=&dist=&locn=&strd_s=&strd_e=&prcd_s=&prcd_e=&sfpd_s=&sfpd_e=&lupd_s=&lupd_e=&sort=nwst

  • Search term: metformin
  • Filter: adults 18-64 AND adults 65+
  • Sort order: most recent first

https://www.iodine.com/drug/metformin/reviews/4

http://sideeffects.embl.de/drugs/4091/

https://www.iodine.com/drug/metformin/fda-package-insert

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