What Diabetes Medication Causes Weight Gain?

Diabetes medicines that cause weight gain are the least preferred nowadays by most physicians because of the increased prevalence of obesity and diabesity.

Diabesity is the co-occurrence of diabetes and obesity. Most of the new treatments are aiming to reduce the person’s body weight in addition to controlling diabetes. Controlling weight in obese diabetic patients might reverse diabetes and prediabetes.

However, as therapies emerge and new drugs are invented, the pandemic of diabesity (Diabetes and Obesity) is shifting toward developing countries. This is because of the cost involved with these new medications.

Commonly used diabetes medicines in developing countries belong to one of the following classes of diabetes medicines:

• Biguanides (Metformin)
• Sulfonylureas (Glimepiride, Glyburide, Gliclazide, and Glipizide)
• Thiozolidendedions (Piolgitazone)
• DPP IV inhibitors (Sitagliptin and Vildagliptin)
• SGLT-2 inhibitors (Dapagliflozin and empagliflozin)
• Insulin

Among these six groups of medicines, only the SGLT-2 inhibitors are associated with some degree of weight loss.

Metformin and DPP IV inhibitors are considered weight-neutral, while the rest of the diabetes medicines cause weight gain.

The majority of the patients are on either Insulin, Sulfonylureas, or metformin. Usually, metformin is given in combination with insulin and sulfonylureas.

GLP-1 class of medicines that cause marked weight loss and are the only approved diabetes medicines that have been approved for weight loss in diabetics and non-diabetics.

These medicines are costly and are rarely used in developing countries. A minority of the affluent class is on GLP-1 analogs.

Here is a cost comparison of oral diabetes medicines:

The Novel medicines that cause weight loss, Jardiance, Farxiga, and Rybelsus are too costly compared to the medicines that cause weight gain.

The bar chart above compares the cost of injectable diabetes medicines. It is very clear that the novel injectable medicines that cause weight loss are very costly compared to insulins that cause weight gain.

The above charts compare the prices of oral and injectable diabetes medications. It is obvious that medicines associated with weight loss are too costly compared to those causing weight gain.

This difference in the prices can shift the diabesity pandemic from western countries to developing countries, adding more burden to the already stressed populations.

Diabetes Medicines that cause Weight Gain:

A low-calorie diet and physical exercise are essential and considered the two pillars of diabetes control, the role of medication can not be ignored. Diabetes Medicines make the third pillar of diabetes control.

A low-calorie diet and exercise are good for weight loss too. However, diabetes medicines may sometimes cause weight gain.

It is important to choose the right medicine for an obese diabetic patient so as the vicious cycle of weight gain, immobility, and uncontrolled diabetes does not begin.

What Diabetes Medication Causes Weight Gain?

Diabetes medicines that cause weight gain are mentioned in the table below:

• Insulin:

Insulin is an anabolic hormone. It is one of the essential hormones the body requires for growth and development.

It causes the entry of nutrients, primarily glucose, into the cells and increases the body’s stores. It increases appetite and especially, if administered in high doses, it can cause the blood sugars to go down, resulting in the activation of the hunger center in the brain.

Insulin causes weight gain. It causes greater weight gain when compared to any of the other oral diabetes medications.

Different insulin formulations may have slightly different weight-inducing properties, however, Insulin detemir is considered to cause the least weight gain among all the insulins [Ref].

Insulin detemir is long-acting basal insulin administered once or twice daily. It is an insulin analog. The exact reason why it is associated with relatively less weight gain is not yet known.

Overall insulin causes a weight gain of about 4 kgs over several months. The weight-gaining effects of different insulins are summarized in the table below:

• Sulfonylureas:

Sulfonylureas are insulin secretagogues. They act by stimulating the Beta-cells of the pancreas to release more insulin. Thus, in essence, they are like insulin.

Different sulfonylureas have slightly different glucose-lowering effects and their half-lives are different too.

Thus, some stay in the blood for longer periods of time while others are relatively shorter acting. This could be one reason why different sulfonylureas have different effects on blood glucose levels and weight.

Gliclazide and Glimepiride are considered to cause less weight gain compared to glyburide and glipizide.

Glyburide was associated with more weight gain compared to combined glyburide and metformin [Ref]. The degree of weight gain also depends on the concomitant medications.

• Thiozolidenedions:

Thiozolidenedions include Rosiglitazone and Pioglitazone. Pioglitazone is commonly used in developing countries while rosiglitazone is now no longer available. The main reason rosiglitazone was banned was because of its association with heart failure.

Like Rosiglitazone, Pioglitazone also causes water retention as a result of reduced renal excretion of sodium and a change in intestinal ionic transport [Ref].

In one study, the weight gain associated with pioglitazone was mostly due to fluid retention. 75% of the weight gain was caused by water retention [Ref].

Pioglitazone is, therefore, specifically, avoided in fluid-overloaded conditions such as heart failure. It can also result in macular edema.

• Meglitinides:

Meglitinides include Repaglinide and Nateglinide. Both these drugs are short-acting insulin secretagogues and cause the release of insulin.

Except for their shorter duration of action, their effect on insulin secretion is the same as sulfonylureas. Repaglinide was observed to cause more weight gain compared to nateglinide [Ref].

Summary of Comparison of oral Diabetes medicines that cause weight gain:

Insulin, Thiazolidinediones, Meglitinides, and Sulfonylureas are diabetes medicines that cause weight gain.

Table: Oral Diabetes medicines that cause weight gain:

Some of these drugs are associated with more weight gain than others. However, the degree of weight gain depends on the concomitant medications and the intensity of the diabetic regimen.

Individuals on intensified regimens and those with frequent hypoglycemia are more likely to gain weight compared to those who are on a less intensified regimen.

Diabetes Medicines that cause Weight Loss:

Weight loss is usually one of the desired side effects of most novel diabetes medications. Diabetes drugs that are associated with the most weight loss are mentioned in the table below:

In Summary:

Most novel diabetes medicines are weight neutral. SGLT2 Inhibitors such as Dapagliflozin, Ertugliflozin, and Empagliflozin, as well as the GLP-1 analogs (Semaglutide, Liraglutide, Dulaglutide, and exenatide), cause weight loss.