Pharma Face-Off: Ozempic vs. Metformin

Even for the savviest patients, managing one’s health while living with diabetes can be a complicated endeavor. While the plethora of available treatment options and anti-diabetic medications can be seen as a blessing, the “analysis paralysis” that such an abundance of choice brings can make a double-edged sword out of the whole situation. Unfortunately, guidance is unlikely to be found by turning to the news or social media, as influencers and advertisements pushing the newest, fanciest drug only add to the confusion.

Speaking of fancy new drugs, Ozempic has entered the market with a splash in recent years, drumming up waves of media attention from news outlets and social media stars alike. Such fervor around an anti-diabetic medication is unusual; staple medications like metformin, which has played a critical role in diabetes treatment for decades, get no airtime whatsoever next to their celebrity successors like Ozempic. To the layperson, such asymmetrical treatment can create the impression that the popular choice (Ozempic) is the better choice – whether for treating one’s diabetes or even for other purposes, like helping to lose some stubborn body fat. But how do Ozempic and metformin stack up?

Comparison

Intended usages

Metformin and Ozempic are alike in that they can both be used for treating type 2 diabetes. In fact, metformin has been a staple first-line choice for patients diagnosed with this condition since as early as the 1960s. Ozempic has only been FDA-approved for use in type 2 diabetics since 2017.

While both drugs are only FDA-approved for type 2 diabetes treatment, they are both often given “off-label” to treat a variety of other conditions. Perhaps the most notorious off-label use case for Ozempic is as a weight loss aid. In fact, semaglutide (the active ingredient in Ozempic) has been explicitly approved in a different formulation (called Wegovy) for that very purpose. You may be surprised to learn, then, that metformin also has a history as a weight loss aid, though it has never received FDA approval for that specific indication. Later on, we will compare the efficacy of these two drugs both as an anti-diabetic and as a weight loss supplement.

Mechanisms of action

Ozempic is simply the brand name for a medication called semaglutide. Semaglutide belongs to a category of medications known as the GLP-1 receptor agonists, all of which rely on a groundbreaking mechanism that capitalizes on the body’s natural endocrine receptors to produce positive results. GLP-1 is a naturally occurring hormone that plays a pivotal role in controlling metabolism, digestion, and blood sugar regulation. By stimulating the receptors that normally respond to GLP-1’s presence, GLP-1 receptor agonist medications like Ozempic promote greater insulin sensitivity, slower digestion, and greater satiety. Ideally, this mechanism produces a range of positive effects in patients, including a reduced appetite, less powerful carbohydrate cravings, greater insulin secretion from the pancreas, and lower and more stable blood sugar levels.

Metformin achieves its outcomes through slightly different means. Classified as a biguanide, metformin primarily affects the liver’s release of glucose and improves the uptake of blood sugar by muscle cells, effectively lowering blood sugar levels. Metformin owes its results in part to its effects on the AMP-activated protein kinase (or AMPK) system – a bodily system that controls the body’s energy balance. By activating AMPK, metformin induces reduced glucose production and increased glucose uptake that provide therapeutic benefits to diabetic patients.

Through their separate means, both of these powerful medications can achieve a range of outcomes for patients that help manage symptoms of diabetes. These primarily include blood sugar regulation, but both drugs have, to varying extents, also been noted for their potential to cause other secondary benefits to those who take them. Weight loss is a prime example of a secondary benefit that has been ascribed to both medications (so much so for semaglutide that it has been FDA-approved in other formulations for this precise use case),  though to varying extents, as we will soon examine.

Dosage

At the outset, it is important to note that the dosage schedule of any medication can vary from patient to patient depending on their particular needs and their doctors’ discretion. Always defer to a doctor or pharmacist’s instructions for any prescribed medication, or consult the literature included with a prescription for dosage instructions.

Metformin is taken orally, typically in the form of an instant-release (IR) or extended-release (XR) tablet. These tablets are intended to be swallowed whole without crushing them or breaking their protective coating. A liquid oral suspension may also be available for metformin.

Adult type 2 diabetic patients taking metformin will typically take their medication one or more times per day, up to 2,500 mg or greater in some cases. Since metformin is often sold in formulations that contain additional medications, such as an insulin-metformin combination tablet, or in various generic forms that may use a variety of coatings to achieve their extended-release effect, the exact timing and frequency for any given formulation may vary significantly.

Compared to metformin, Ozempic’s administration schedule requires far fewer applications than metformin’s daily dosage schedule. Ozempic is an injectable medication, and patients are only required to receive injections every week, typically. Ozempic users may have their dosages titrated upwards over several months, increasing the amount injected each week slightly at regular intervals. For example, a common schedule might see patients begin with 0.5 mg injected weekly for four weeks, then increase the dosage by 0.5 mg, and repeat that pattern every four weeks up to a maximum dosage of 4 mg weekly. This sustained activity of Ozempic makes it a very convenient choice in many regards, though patients with an aversion to needles and those without a convenient way to store or transport the vials and syringes needed may find an oral solution preferable.

Efficacy

A fair comparison of these two drugs’ efficacy should consider the multiple ways in which they are often used. Simply comparing their efficacy in controlling type 2 diabetes symptoms, for example, would neglect to take into account how the drugs compare in their potency as a weight loss aid.

Starting with their primary roles as anti-diabetic medications, both medications have been demonstrated to be effective options for treating type 2 diabetes and appear to perform similarly in terms of the outcomes they tend to produce. Both have been shown to reduce A1C levels by approximately 1% to 2%, which is often used as a measure of long-term patterns in blood glucose levels. Since diabetes management tends to focus on blood sugar maintenance, such a reduction in A1C or blood sugar generally equates to success as an anti-diabetic medication.

With respect to their roles as weight loss aids, however, the efficacy of these drugs begins to diverge. Perhaps unsurprisingly, Ozempic emerges as the clear winner in this regard. In one study, patients taking Ozempic for one year lost 10% more body weight than their counterparts who were given metformin instead.

Cost

When it comes to cost, these drugs may not be on equal footing depending on your insurance coverage. Without insurance, the brand-new Ozempic comes at a steep premium relative to the decades-old and generically sold metformin. The details will vary, but a typical Medicare co-pay for Ozempic could range from $25-$1000, versus $8 or less for metformin.

Whether either medication is covered under an insurance plan depends on the plan, but patients taking Ozempic for weight loss may also be unpleasantly surprised by the fact that insurers tend not to cover off-label prescriptions. The cost difference can make Ozempic difficult to access for many, often making metformin the more realistic choice despite other factors potentially weighing in favor of Ozempic. To add to the bad news, it is unlikely that a generic semaglutide will appear on the market for many years, owing to the patent protection laws that grant pharmaceutical manufacturers a monopoly over new releases for a fixed amount of time before allowing generic competitors to enter the ring.

Risks and side effects

Despite varying greatly in their mechanisms of action and routes of administration, metformin and Ozempic share a fairly similar profile of side effects and risks. Both drugs can lead to gastrointestinal distress, including nausea, diarrhea, vomiting, and abdominal cramping, though these tend to be more prominent in Ozempic users. Metformin, on the other hand, tends to cause a greater incidence of headache, fatigue, and muscle weakness than Ozempic. Since both medications are used to lower blood sugar, hypoglycemia is a somewhat common occurrence, particularly in non-diabetic patients taking these medications for weight loss.

Conclusion

Having compared Ozempic and metformin across multiple categories, the answer as to which option is superior is a resounding “It depends”. Ozempic seems to offer a clear advantage when it comes to weight loss, but both drugs perform competitively in the treatment of type 2 diabetes. Which drug one chooses might therefore come down to non-medical factors, like the affordable cost of metformin, or the preference to inject once weekly rather than take a pill every day. Ultimately, however, we must stress that a decision between these two medications should only be made by a doctor, as there are complex factors beyond the scope of this article that may tip the scales in either direction.

The data used in the table above was created on September 1, 2023.