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Improving diabetes prevention with benefit based tailored treatment: risk based reanalysis of Diabetes Prevention Program

BMJ 2015; 350 doi: (Published 19 February 2015) Cite this as: BMJ 2015;350:h454

Metformin Journey: Past, Present and Future.

We read this research paper with interest, a thought provoking article. The benefit of metformin, however, was seen almost entirely in patients in the top quarter of risk of diabetes. No benefit was seen in the lowest risk quarter [1]. A well known fact is “prevention is better than cure”; epidemiological studies reveal that being physical active improves longevity [2], also there is report from metaepidemiological study that therapeutic life style changes may be potentially as effective as many drug interventions in the secondary prevention of coronary heart disease, stroke, heart failure, and prediabetes [3].

Metformin was introduced in Europe in the 1970s and approved in the United States in 1995and it has an excellent therapeutic index for diabetes [4]. It is a biguanide developed from galegine, found in Galega officinalis (French lilac) [5]. Clinical trials showed that metformin has advantages over other agents used in the management of type II diabetes [6], and has documented effectiveness in diabetes prevention for subjects at a high risk [7]. In the United Kingdom Prospective Diabetes Study, metformin was associated with less weight gain and fewer hypoglycaemic attacks than are insulin and sulphonylureas, and it also proved to be effective in decreasing diabetes-related death, myocardial infarction, and stroke [8]. Currently because of proven benifits, metformin is one of the most frequently prescribed drugs in patients with type 2 diabetes all over the world.

Regarding future aspects:

Metformin has received increased attention due to the identification of anticancer effects; the risks of cancer among metformin users were significantly lower than those among non-metformin users. Also the use of metformin in diabetic patients was associated with significantly lower risks of cancer mortality and incidence [9]. Metformin could become a more attractive chemoprevention agent in future than its present role in management of type 2 diabetes mellitus.

1. Sussman JB, Kent DM, Nelson JP, Hayward RA. Improving diabetes prevention with benefit based tailored treatment: risk based reanalysis of Diabetes Prevention Program. BMJ 2015;350:h454.
2. Lee I-M, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet 2012;380:219-229.
3. Naci H, Ioannidis JPA. Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study. BMJ 2013;347:f5577
4. Bailey CJ, et al. Metformin. N Engl J Med 1996;334:574–9.
5. Cusi K, Defronzo RA. Metformin: a review of its metabolic effects. Diabetes Reviews. 1998;6:89–131.
6. Bolen S, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med 2007;147:386–99.
7. Knowler WC, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393–403.
8. UKPDS Group, Turner RC, et al. Effects of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854–865.
9. Noto H, Goto A, Tsujimoto T, Noda M. Cancer Risk in Diabetic Patients Treated with Metformin: A Systematic Review and Meta-analysis. PLoS ONE. 2012; 7(3): e33411. doi:10.1371/journal.pone.0033411

Competing interests: No competing interests

24 February 2015
Dr.Rajiv Kumar
Associate Professor, Deptt. of Pharmacology
Dr.Jagjit Singh, Assistant Professor & co author.
Government Medical College & Hospital, Chandigarh 160030. INDIA