Table of Content

• What is metformin?

• How does metformin work?

• Relation between metformin and weight loss

• Weight loss effect of metformin in diabetics

• Weight loss effect in non-diabetic

• Why increase the metformin dose?

• Side effects of metformin

• Contraindication to metformin

• Take-Home Points

• FAQ on Metformin and Weight Loss

Introduction

 Metformin is a promising drug for the management of type 2 diabetes. Both the American Diabetes Association  (ADA) and the American Association of Clinical Endocrinologists (AACE) recommend it as 1st line treatment.

If you are a diabetic patient you are familiar with the name (Glucophage) metformin or you may have heard about it. Then you might have come across a dilemma of metformin; does metformin cause weight loss? If yes then how and why metformin causes weight loss? Let's understand this grey area.

What is metformin?

A most effective drug for type 2 diabetes management. Back in the 20 century, a compound was extracted from French lilac, which was used for anti-diabetic, anti-hypertension, and anti-ageing actions in medieval times.

This was first observed by Emil Werner in 1922. Its antidiabetic action was 1 discovered by Slotta and Tschesche.

Metformin is the 1 line drug prescribed for the management of type 2 diabetes. It not only decreases blood glucose production in the liver but also improves insulin sensitivity for better management.

It is generally given as monotherapy or in combination with insulin therapy, sulfonylureas, liraglutide, nateglinide, gliptins, dapagliflozin, etc.

Here is the structure of metformin:

Metformin is one of the drugs with complex actions with simpler structures.

How does metformin work?

Metformin is a highly potent drug with a complex mechanism of action. It is an FDA-approved drug for the management of hyperglycemia specifically in type 2 diabetes mellitus.

Metformin reduces serum glucose levels by the following mechanism:

1. Act as an insulin sensitizer.

2. Suppresses gluconeogenesis (glucose production from the non-carbohydrate substrate).

3. Stimulate glucose transport in muscles.

4. Stimulate glucose utilization by the gut.

5. Activated AMPK (AMP-activated protein kinase)- reduces the energy expenditure at the cellular level. 

AMPK is important for the metabolism of glucose and fatty acids. 

There is no cure for diabetes mellitus yet but the right combination of a healthy lifestyle and medication will improve your condition a lot.

If you follow the right routine your health will be improved with decreased future health risks like kidney damage, vision problems, increased weight, and nerve damage.  It also helps to manage diabetic-linked PCOD and fatty liver conditions. 

Relation between metformin and weight loss

Here comes the grey area, whether metformin causes weight loss or not. This relation is due to the decreased calorie intake and increased energy expenditure. 

Weight loss due to metformin is independent of age and sex.

Metformin is directly and indirectly linked with weight loss. It promotes modest weight loss via cardiometabolic effects through various alterations in neuronal appetite center, liver glucose metabolism, muscle glucose utilization, and lactate production.

It shows the following actions:

• Increases the weight loss promoting chemical incretin, anorectic hormone peptide YY.

• Induces cerebral metabolic changes.

• Decreases the function of ghrelin. (commonly known as hunger hormone).

CNS effect:

• Decreases hypothalamic neurons by suppressing AMPK.

• Increases leptin sensitivity.

• Increases GLP-1(glucagon-like peptide)

• Suppresses appetite.

Gastrointestinal effects:

• Nausea.

• Alter the bile absorption.

• Diarrhea and bloating.

Hepatic (liver) effects

• Decreases hepatic glucose utilization.

• Decreases insulin requirement.

Ageing effect

• Reduction in obesity.

Weight loss effect of metformin in diabetics

Metformin is a preferred drug specifically for obese diabetic patients for a particular reason which is weight loss. Comparatively other antidiabetic drugs show weight gain as their potential side effect. Hence metformin becomes the preferred drug with better outcomes. 

One study showed the metformin-treated group showed 3.8kg of weight loss compared to sulfonylurea-treated group in 6 months. Another study states 2.7 kg weight loss over 4 years duration while another group showed 5 kg weight gain with rosiglitazone. 

The largest study was conducted, by the Diabetes Prevention Programme (DPP).  They conclude-

• Metformin initiation reduces diabetes incidence by 31% in 3 years.

• Patients randomized to metformin experience an average weight reduction of 2.1kg.

• Weight change is associated with adherence.

• Weight loss persisted in the extended 10-year examination. 

It shows mild to moderate git side effects.  It is recommended by the AACE guidelines on Obesity management that metformin is used for patients with insulin intolerance or prediabetic only. 

Bottom line- it shows a significant reduction in weight with obese diabetes. 

Weight loss effect in non-diabetic

Metformin has been in the market for over 60 years with promising effects for diabetic patients. You must be wondering if it is effective on nondiabetics for weight loss too. 

Primarily metformin is not a weight-reducing agent. One study concludes metformin shows significant weight reduction in potential insulin-resistant patients. 

European society of endocrinology, conducted a study for a 2-month duration, which supports the statement, that metformin is effective for weight loss in non-diabetic obese people.  

Weight reduction in non-diabetics is still uncertain with insulin sensitivity, because of a lack of strong data, and extended-duration studies. 

Therefore, metformin is effective for weight loss in non-diabetics obese people as per the short-duration studies. To confirm the long-term benefits and seamless results more studies are required. 

Why increase the metformin dose?

Metformin has a dose-dependent hypoglycemic effect. This indirectly implies a weight loss effect. It was studied on Japanese patients with a dose of 1500mg which gradually increased up to 2250mg and results were positive. 

Hence increasing the metformin is directly linked with hypoglycemic actions. 

Side effects of metformin

The most common side effects seen with metformin are:

• Nausea

• Vomiting

• Vitamin B12 deficiency 

• Loss of appetite

• Metallic taste in my mouth 

• Diarrhea  

Contraindication to metformin

• If you have any of the following conditions, you should not take metformin-

• Renal dysfunctioning

• Heart disease

• Hypersensitivity to metformin

• Acute or chronic metabolic acidosis

• Impaired hepatic function

You need to take precautions if-

• Your age>80 years 

• You have acute myocardial infarction

• You undergo any radiological surgery

• You are alcoholic

Take-Home Points

• Metformin is the choice of drug in the management of type 2 diabetes. 

• Metformin induces weight loss independent of age and sex.

• Weight loss and diabetes management are complemented by combining a healthy lifestyle and medication. 

• All the effects of metformin are associated with strong adherence to medication for long-term benefits.