Behnoush Hajian/Science Photo Library/Getty Images
Metformin has been prescribed to people with type 2 diabetes to manage blood sugar for more than 60 years, but scientists haven’t been exactly sure how it works. A new study suggests it works directly in the brain, which could lead to new types of treatment. The study, carried out by researchers from the Baylor College of Medicine in the US, identifies a brain pathway that the drug seems to work through, in addition to the effects it has on biological processes in other areas of the body……..Continue reading…..
By David Nield
Source: ScienceAlert
.
Critics:
Treatment guidelines for major professional associations, including the European Association for the Study of Diabetes, the European Society for Cardiology, and the American Diabetes Association, describe evidence for the cardiovascular benefits of metformin as equivocal. A 2020 Cochrane systematic review did not find enough evidence of reduction of cardiovascular mortality, non-fatal myocardial infarction or non-fatal stroke when comparing metformin monotherapy to other glucose-lowering drugs, behavior change interventions, placebo or no intervention.
The use of metformin reduces body weight in people with type 2 diabetes in contrast to sulfonylureas, which are associated with weight gain. Some evidence shows that metformin is associated with weight loss in obesity in the absence of diabetes. Metformin has a lower risk of hypoglycemia than the sulfonylureas, although hypoglycemia has uncommonly occurred during intense exercise, calorie deficit, or when used with other agents to lower blood glucose.
Metformin modestly reduces low density lipoprotein and triglyceride levels. In individuals with prediabetes, a 2019 systematic review comparing the effects of metformin with other interventions in the reduction of risk of developing type 2 diabetes found moderate-quality evidence that metformin reduced the risk of developing type 2 diabetes when compared to diet and exercise or a placebo.
However, when comparing metformin to intensive diet or exercise, moderate-quality evidence was found that metformin did not reduce risk of developing type 2 diabetes and very low-quality evidence was found that adding metformin to intensive diet or exercise did not show any advantage or disadvantage in reducing risk of type 2 diabetes when compared to intensive exercise and diet alone.
The same review also found one suitable trial comparing the effects of metformin and sulfonylurea in reducing the risk of developing type 2 diabetes in prediabetic individuals, however, this trial did not report any patient-relevant outcomes. In those with polycystic ovary syndrome (PCOS), tentative evidence shows that metformin use increases the rate of live births. This includes those who have not been able to get pregnant with clomiphene.
Metformin does not appear to change the risk of miscarriage. A number of other benefits have also been found both during pregnancy and in nonpregnant women with PCOS. In an updated Cochrane review on metformin versus placebo/no treatment before or during IVF/ICSI in women with PCOS no conclusive evidence of improved live birth rates was found.
In long GnRH-agonist protocols there was uncertainty in the evidence of improved live birth rates but there could be increases in clinical pregnancy rate. In short GnRH-antagonist protocols metformin may reduce live birth rates with uncertainty on its effect on clinical pregnancy rate. Metformin may result in a reduction of OHSS but could come with a greater frequency of side effects. There was uncertainty as to metformin’s impact on miscarriage.
The evidence does not support general use during pregnancy for improving maternal and infant outcomes in obese women. The United Kingdom’s National Institute for Health and Clinical Excellence recommended in 2004 that women with PCOS and a body mass index above 25 be given metformin for anovulation and infertility when other therapies fail to produce results.
UK and international clinical practice guidelines do not recommend metformin as a first-line treatment or do not recommend it at all, except for women with glucose intolerance. The guidelines suggest clomiphene as the first medication option and emphasize lifestyle modification independently from medical treatment. Metformin treatment decreases the risk of developing type 2 diabetes in women with PCOS who exhibited impaired glucose tolerance at baseline.
A total review of metformin use during pregnancy compared to insulin alone found good short-term safety for both the mother and baby, but safety in the longer term is unclear. Several observational studies and randomized controlled trials found metformin to be as effective and safe as insulin for the management of gestational diabetes. Nonetheless, several concerns have been raised and evidence on the long-term safety of metformin for both mother and child is lacking.
Compared with insulin, women with gestational diabetes treated with metformin gain less weight and are less likely to develop pre-eclampsia during pregnancy. Babies born to women treated with metformin have less visceral fat, and this may make them less prone to insulin resistance in later life. The use of metformin for gestational diabetes resulted in smaller babies compared to treatment with insulin.
However, despite initially lower birth weight, children exposed to metformin during pregnancy had accelerated growth after birth, and were heavier by mid-childhood than those exposed to insulin during pregnancy. This pattern of initial low birth weight followed by catch-up growth that surpasses comparative children has been associated with long-term cardiometabolic disease.
A systematic review and meta-analysis of metformin, published in 2024, found that it is safe and effective in managing gestational diabetes or diabetes in pregnancy with no adverse impact on the mother or the child after eleven years of childbirth. Metformin use is typically associated with weight loss. It appears to be safe and effective in counteracting the weight gain caused by the antipsychotic medications olanzapine and clozapine.
Although modest reversal of clozapine-associated weight gain is found with metformin, primary prevention of weight gain is more valuable. Metformin may reduce the insulin requirement in type 1 diabetes, albeit with an increased risk of hypoglycemia. Metformin is contraindicated in people with:
- Severe renal impairment (estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2)
- Known hypersensitivity to metformin
- Acute or chronic metabolic acidosis, including diabetic ketoacidosis (from uncontrolled diabetes), with or without coma
The most common adverse effect of metformin is gastrointestinal irritation, including diarrhea, cramps, nausea, vomiting, and increased flatulence. Metformin is more commonly associated with gastrointestinal adverse effects than most other antidiabetic medications. The most serious potential adverse effect of metformin is lactic acidosis; this complication is rare, and seems to be related to impaired liver or kidney function.
Metformin is not approved for use in those with severe kidney disease, but may still be used at lower doses in those with kidney problems. Gastrointestinal upset can cause severe discomfort; it is most common when metformin is first administered, or when the dose is increased. The discomfort can often be avoided by beginning at a low dose (1.0 to 1.7 g/day) and increasing the dose gradually, but even with low doses, 5% of people may be unable to tolerate metformin.
Use of slow or extended-release preparations may improve tolerability. Long-term use of metformin has been associated with increased homocysteine levels and malabsorption of vitamin B12. Higher doses and prolonged use are associated with increased incidence of vitamin B12 deficiency, and some researchers recommend screening or prevention strategies.
Leave a Reply