Hi Mr Khan,

I would like to write here that Metformin hydrochloride is a type of antidiabetic medicine called a biguanide. It works in a number of ways to lower blood sugar levels in people with type 2 diabetes. Firstly it increases the sensitivity of muscle cells to insulin. Secondly it reduces the amount of sugar produced by cells in the liver. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

Metformin (brand name Glucophage, Glucophage XR, Glumetza, Riomet) is a member of a class of drugs called biguanides that helps lower blood glucose levels by improving the way the body handles insulin namely by preventing the liver from making excess glucose and by making muscle and fat cells more sensitive.

Metformin may help people with diabetes to lose weight by lowering their appetites. Insulin makes people overweight by acting on the brain to cause hunger making the liver manufacture fat and fill fat cells in the stomach.

Metformin alone (Glucophage® XR) At first 500 mg once daily with the evening meal. Your doctor may increase your dose if needed until your blood sugar is controlled. However, the dose is usually not more than 2000 mg per day. Metformin alone (Glumetza®) At first 500 mg once a day taken with the evening meal.

Positive Effects of Metformin:

1) Metformin Treats and Prevents Type 2 Diabetes

2) Metformin Improves Insulin Resistance

3) Metformin Treats Symptoms of PCOS

4) Metformin May Help Prevent and Treat Cancer

5) Metformin Protects the Heart

6) Metformin Lowers Cholesterol

7) Metformin Causes Weight Loss

8) Metformin May Improve Erectile Dysfunction

9) Metformin Slows Aging

10) Metformin May Protect Against Gentamicin (Antibiotic) Damage

Already Metformin is being used outside of diabetes. Polycystic ovary syndrome (PCOS) is a hormonal disorder in women that is linked to insulin resistance and type 2 diabetes. While it is not explicitly approved, doctors sometimes prescribe metformin for PCOS off-label even for people who do not have type 2.

Reducing the dosage of Metformin or stopping it altogether is safe in some cases. However, this should only be done in collaboration with your doctor. Some people who change their lifestyle by increasing exercise and losing weight are able to stop taking the medication.

Non-diabetic Weight Loss with Metformin. While the Food and Drug Administration has not approved metformin for weight loss in the United States, some physicians are starting to utilize this medication in an off-label manner to decrease weight in overweight or obese patients.

Metformin is used with a proper diet and exercise program and possibly with other medications to control high blood sugar. It is used in patients with type 2 diabetes. Controlling high blood sugar helps prevent:

1. kidney damage,

2. blindness,

3. nerve problems,

4. loss of limbs, and

5. sexual function problems.

Metformin reduces blood sugar levels and is approved by the FDA for treatment of type 2 diabetes. In women with infertility due to polycystic ovarian syndrome (PCOS), trials found metformin plus Clomid to be more effective than Clomid alone in ovulation induction.

The more common side effects of metformin include: •heartburn. •stomach pain. •nausea or vomiting. •bloating. •gas. •diarrhea. •constipation. •weight loss.

Metformin is quiet safe for Patients and it doing Excellent than harm.

Regards,

Dr Ahsan

Response to therapy in diabetics related to many factors. key factors are duration of DM, base line glycemic control, presence of macro and micro-vascular complications, drug territoriality, BMI , physical activity. In addition beta cell mass, and severity of insulin resistance are key areas to be covered. Thus treatment is individualized. Studies have also proved that initially the drug that do pretty well doesn't do good after some time. like response to metformin might be very good initially but after some time (1-2 years) response is not that good thats why either we need to switch on to other drug, or add on therapy or titrate the dose of same drug.

All these factors may be contribute in your study. Dosage of metformin, type (standard or extended release) efficacy of co-administered drugs, drug-drug interactions, all affect glycemic control.

Please also see one of my answers discussing factors affecting HbA1c reliability.

Hope you got answer!

Regards!

Genetics do play role overall in pathophysiology of type 2 DM. looking at spectrum of metformin in particular is important. like its role in weight reduction, NAFLD, carcinoma breast, ovaries, portal hypertension and many many other areas under study. this may open various channels to get benefits of this drug much beyond our expectations in future. It might change genetic understanding of DM and many other diseases in future.

Thanks Ahsan and Shafat

I am grateful indeed and i acknowledge that playgrounds for metformin are beyond diabetes and now even some research is recommending its use in cancer even.

i m not denying any of these roles. I just wanted to highlight and have opinion on these discovered mutations/polymorphisms where sometimes metformin is not that effective. In the practice we routinely have metformin stays with add ons as Dr Shafat has-mentioned but these genetic changes in few will definitely not help life or long-term therapy. It , to me seems important to understand the pharmacoogenomic part of metformin where it may not be useful.

I need to understand about the role of genes here. if you could specifically highlight the genetic aspects of metformin that will rather improve my understanding. A person may not show the desirable pharmacological response of he carries the genes which make him kind of less responsiveness or resistant to metformin.

Still grateful for your additions and explanations.

Regards.

I agree and recommend the comments given by Dr Shafer Khatoon. Well thought of comment.

Grateful to everybody for their time and effort

Look i understand the polygenic nature of T2DM and i understated the the general role of responders and non-responders to metformin.

my question specifically targets the role of SLC22A2rs316019 and SLC47A2 rs12943590 and were probably associated with good response in comparison to patients who carry the G‐allele type.

So if some diabetologist or molecular specialist on this forum elaborate how they can be linked with pre-treatment assessment of T2DM patients for these genetic changes?

The question targets the roles of these genetic changes? can molecular pharmaco-genomics help here in future?????

Regards

There are several studies regarding this. The researchers performed a three-stage genome-wide association study (GWAS) of 13,123 participants to identify genetic variants associated with differences in metformin response, and found a common variant of the gene SLC2A2 that was correlated with a strong response to the drug.

This finding is true, because the gene encodes GLUT2, a glucose transporter protein responsible for regulating the movement of glucose between the liver, the blood and the kidneys.

Gene expression data from 1,226 human liver samples confirmed that people with this variant had less GLUT2 in the liver and other metabolic tissues, which led to a reduced ability to manage blood glucose. Metformin, which slows the liver's production of glucose, appears to be able to reverse this deficit, which could explain its best efficacy in these patients.

Dear

Thanks Sarmistha Sarkar, this was spot and seriously helped me a lot in understanding the concept.

Tx a lot

You can benefit from the following links.

1. Singh S, Usman K, Banerjee M. Pharmacogenetic studies update in type 2 diabetes mellitus. World Journal of Diabetes. 2016;7(15):302-315. doi:10.4239/wjd.v7.i15.302.

2. Smushkin G, Vella A. Genetics of Type 2 Diabetes. Current opinion in clinical nutrition and metabolic care. 2010;13(4):471-477. doi:10.1097/MCO.0b013e32833a558d.

3. Mousavi S, Kohan L, Yavarian M, Habib A. Pharmacogenetic variation of SLC47A1 gene and metformin response in type2 diabetes patients. Molecular Biology Research Communications. 2017;6(2):91-94.

4. Elizabeta Topi.THE ROLE OF PHARMACOGENETICS IN THE TREATMENT OF DIABETES MELLITUS. J Med Biochem 2014; 33 (1).

https://www.dovepress.com/a-two-stage-study-identifies-two-novel-polymorphisms-in-prkag2-affecti-peer-reviewed-fulltext-article-PGPM,kindly check this link.

https://www.oatext.com/genetic-approach-in-personalized-medicine-in-type-2-diabetes.php,u can follow this link.

Dear Sikandar Hayat Khan . See the following useful RG links : Article Pharmacogenetics of Type 2 Diabetes-Progress and Prospects

https://www.dovepress.com/a-two-stage-study-identifies-two-novel-polymorphisms-in-prkag2-affecti-peer-reviewed-fulltext-article-PGPM

Article Pharmacogenetics in type 2 diabetes: Influence on response t...

Kindly see also the following useful RG links: https://www.sciencedirect.com/science/article/abs/pii/S0378111922002013

Article Glucose metabolism-related gene polymorphisms as the risk pr...

https://www.frontiersin.org/articles/10.3389/fphar.2018.00320/full

https://www.nature.com/articles/tpj201654

Role of Metformin in invasive disease-free survival in breast cancer confirmed in a placebo-controlled trial

For details, please gander through this article in JAMA:

Article Effect of Metformin vs Placebo on Invasive Disease-Free Surv...

Also check please the following useful RG links: Article Pharmacogenetics in type 2 diabetes: precision medicine or d...

https://www.intechopen.com/chapters/69844

https://www.pharmacytimes.com/view/genetics-impact-metformin-response-to-diabetes

Article SLC22A1 rs622342 Polymorphism Predicts Insulin Resistance Im...