Bibliographic record
Abstract
We write to reflect upon the unusual ‘journey’ of the antidiabetic drug metformin, an agent with a story that is somewhat different from the other drugs. It is sometimes the case that a new drug will be introduced with great promises, but over the course of time may eventually be withdrawn from markets because of safety concerns. In the case of metformin, the drug was regarded with suspicion during the initial years of its availability, and was even banned in many countries including the USA.1, 2 Time has changed the fate of the drug, and it is now one of the most prescribed oral hypoglycaemic drugs in the world, either alone or in combination products. The interesting tale of metformin begins with its synthesis by Werner and Bell in 1922 in Dublin. In 1929, Slotta and Tschesche demonstrated its glycaemic effects in rabbits. After this many years elapsed before attention was once again focused upon metformin (the discovery of insulin was also unfolding during this period). The French physician, Sterne was the first to test metformin on humans for the therapy of diabetes, coining the name ‘Glucophage’ (glucose eater) for metformin. Metformin found a place in British National Formulary in 1958, and was approved in Canada in 1972, but another two decades elapsed before it gained approval from the US Food and Drug Administration. Glucophage was first branded formulation of metformin marketed in the USA in 1995. In more recent times, it is of interest to note the latest World Health Organization Model List of Essential Medicines (18th edition from April 2013) references only two oral antidiabetics (metformin and glibenclamide). Despite beneficial effects of metformin (less hypoglycaemia and lost weight) reported in well-regarded journals, the wider acceptance of metformin took a very long time, mostly because of apprehension regarding lactic acidosis (as was observed with phenformin). The UK Prospective Diabetes Study (UKPDS), one of the benchmark studies, has explored the benefits of metformin, revealing that its use confers reduced risk of myocardial infarction and overall mortality.1 This finding lends support for selection of metformin as a first choice drug for type 2 diabetes in obese and overweight patients. Finally, in 2012, diabetes experts from the USA and Europe declared metformin should be the first drug choice for all patients with type 2 diabetes, completing a rather long journey to this endpoint.2 Now the role of metformin has progressed further in disease management. Recent data shows survival benefits and anti-aging effects of the drug,3 adding evidence for considering metformin as the mainstay in treatment for type 2 diabetes. There is now evidence to support a role for metformin for prevention of obesity and metabolic syndrome,3 with the pattern of metformin-related weight reduction being different from that associated with caloric restriction and more closely resembling that associated with the effects of exercise. Moreover, long-term therapy with metformin appears to be safe for preventing or delaying type 2 diabetes.1 Already metformin therapy has been considered as the most cost effective alternative to life style modification for prevention and control of diabetes. Epidemiological studies have shown that certain malignancies such as those affecting the pancreas, liver, colorectum, breast and endometrium occur more commonly in patients with type 2 diabetes than the general population. Among cancer patients, pre-existing diabetes is associated with an increased risk of all-cause mortality. It is unclear whether the increased mortality is a consequence of obesity or of the other impaired health conditions associated with diabetes, such as hyperglyceamia, hyperinsulinaemia and inflammatory processes. A recent meta-analysis and large cohort studies have concluded that the use of metformin for those with diabetes appears to be associated with a lower risk of cancer incidence and cancer-related mortality, again providing additional evidence for choosing this drug as first line therapy in type 2 diabetes.4-6 Type 2 diabetes and even insulin treatment may be associated with an increased risk of dementia. Recent evidence from a large observational study suggests that treatment with metformin may significantly lower dementia risk in the diabetes.7 After a long and at times difficult journey, metformin has now clearly established a place in the management of diabetes, and is also used to treat conditions like gestational diabetes and polycystic ovary syndrome, and is showing early promise for other indications such as cancer prevention and modulation of dementia risk. Sonal Sekhar, MPharm Girish Thunga, MPharm A Suhaj, MPharm Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences Manipal University Manipal, India E-mail: sonalsekhar@gmail.com
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.008 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".