Over the past few years, "weight-loss injections" have become one of the most intriguing topics in both the medical community and daily conversations. The leading medications in this category, Ozempic (active ingredient semaglutide) and Mounjaro (active ingredient tirzepatide), were originally developed for the treatment of Type 2 diabetes; however, they are molecules that have garnered massive global attention because they suppress appetite and induce significant weight loss while regulating blood glucose.
So, what exactly do these drugs alter within the body? In this article, we look beyond marketing rhetoric to explain the underlying physiology of these medications—namely, the glucagon hormone, hepatic glucose production, and the GLP-1 mechanism of action—from an expert perspective.
First, a minor but crucial correction: These medications are sometimes referred to colloquially as "GLP-1 blockers." However, the exact opposite is true. Ozempic and Mounjaro do not block the GLP-1 receptor; they activate it. Therefore, their correct medical classification is GLP-1 receptor agonists (GLP-1 RAs for short). Mounjaro takes this a step further by activating both the GLP-1 and GIP receptors, making it a dual agonist. This distinction is key to understanding why these medications are so effective.
What is Glucagon? The Body's "Release Sugar" Command
When people think of blood sugar, most only know of insulin. Yet, blood glucose homeostasis is a delicate dance between two antagonistically operating hormones: insulin and glucagon. Glucagon is a hormone secreted by the alpha cells of the Islets of Langerhans in the pancreas. Its primary function is roughly the inverse of insulin. While insulin dictates "lower blood sugar, store it," glucagon issues the command to "raise blood sugar, release it from storage.”
The classic scenario in which glucagon comes into play is fasting. When you do not eat for an extended period, your blood glucose begins to decline. Alpha cells detect this decline and secrete glucagon, which enters the bloodstream to reach its primary target: the liver. In a healthy body, this system operates flawlessly: insulin dominates following a meal, while glucagon takes over during fasting, thereby maintaining blood glucose within a narrow physiological range.
Where and How Does Glucagon Act in the Liver?
The primary stage where glucagon plays its leading role is the liver. The liver acts as the body's central glucose reservoir and manufacturing plant. Glucagon binds to glucagon receptors on the surface of liver cells (hepatocytes). This receptor is a G-protein-coupled receptor; upon binding, an intracellular signaling cascade is initiated: the enzyme adenylate cyclase is activated, cAMP levels rise, and this, in turn, activates a key enzyme called Protein Kinase A (PKA).
What follows can be thought of as a series of metabolic switches flipped on and off by PKA. Fundamentally, three processes occur in the liver:
- Glycogenolysis: The liver stores glucose as a reserve fuel in the form of glycogen. Glucagon breaks down (lyses) this stored glycogen back into glucose and releases it into the bloodstream, serving as the short-term mechanism that rapidly elevates blood sugar.
- Gluconeogenesis: When glycogen stores are depleted (e.g., during prolonged fasting), the liver produces new glucose from non-carbohydrate sources—such as amino acids, lactate, and glycerol. Meaning "the creation of new sugar," gluconeogenesis is a longer-term process stimulated by glucagon.
- Inhibition of Glycolysis: The third and complementary effect is glucagon's inhibition of the liver's own glucose consumption. This is a logical regulation: while the liver is laboriously producing and releasing glucose into the blood, it should not simultaneously burn that same glucose internally. The manufactured glucose is intended to exit the cell and join the systemic circulation.
Through these three processes, the liver maintains blood glucose at survival-sustaining levels, even while we sleep. Thus, glucagon is intrinsically a vital and beneficial hormone. The problem arises when this system dysfunctions.
How Do Things Go Wrong in Type 2 Diabetes and Insulin Resistance?
In a healthy individual, glucagon is suppressed after eating; because there is no longer a need for the liver to produce additional sugar. In individuals with Type 2 diabetes and advanced insulin resistance, this balance is disrupted on two fronts simultaneously:
First, cells become resistant to insulin; meaning insulin knocks on the door, but the cells do not adequately take the glucose inside.
Second—and often overlooked—the alpha cells continue to inappropriately secrete excess glucagon.
The glucagon, which should be silenced after a meal, remains active and continuously sends the liver the command to "produce sugar, release sugar." The result is a two-sided catastrophe: On one hand, blood glucose cannot enter the cells; on the other hand, the liver continuously pumps out new sugar via gluconeogenesis. This is precisely why fasting blood glucose, in particular, remains high in Type 2 diabetes; the liver has relentlessly produced sugar throughout the night. Therefore, diabetes is not merely a disease of "insulin deficiency," but equally a disease of "glucagon excess.”
The revolutionary aspect of modern medications is their ability to precisely target this second point, glucagon. To understand these drugs, one must familiarize themselves with a final concept: The Incretin Effect.
The Incretin Effect: The Intestine's Smart Hormones
Scientists noticed something fascinating years ago: The amount of insulin secreted when a specific amount of glucose is ingested orally is significantly greater than the insulin secreted when the identical amount of glucose is administered intravenously. This indicated that the intestine, upon receiving nutrients, sends an anticipatory signal to the pancreas declaring, "get ready, sugar is coming." These signaling hormones were named Incretins.
There are two primary Incretin hormones:
GLP-1 (Glucagon-Like Peptide-1): Secreted by cells in the lower portion of the small intestine.
GIP (Glucose-Dependent Insulinotropic Polypeptide): Secreted from the upper portion of the small intestine.
The physiological effects of the GLP-1 hormone are exactly what one might dream of for a diabetes and obesity drug:
- It increases insulin secretion from the pancreas (but only when blood sugar is high; this is a critical safety feature).
- It suppresses glucagon secretion from the pancreas, thereby curbing the liver's excessive glucose production.
- It delays gastric emptying, thereby prolonging the feeling of fullness and smoothing out postprandial glucose spikes.
- It acts on the appetite centers in the brain, creating a sense of satiety and reducing appetite.
How Does Ozempic (Semaglutide) Provide Benefit?
Semaglutide, the active ingredient in Ozempic, is a molecule synthesized in the laboratory to mimic the natural GLP-1 hormone. However, it has been so ingeniously designed that the DPP-4 enzyme cannot easily degrade it. Thanks to this, while the natural hormone disappears in minutes, Semaglutide maintains its efficacy in the body for days. This prolonged duration of action makes once-weekly injection therapy possible.
By binding to the GLP-1 receptor, Semaglutide potently and continuously activates all the aforementioned GLP-1 effects:
- It lowers blood glucose by enhancing the postprandial insulin response.
- It suppresses glucagon, curbing unnecessary hepatic gluconeogenesis; thus, fasting blood glucose, in particular, is brought under control.
- By delaying gastric emptying and altering appetite signals in the brain, it ensures the individual eats less and feels full more quickly. This is the fundamental reason for the weight loss.
A key point regarding safety: Semaglutide's insulin-stimulating effect is glucose-dependent. Meaning, it only stimulates the pancreas when blood glucose is elevated, and it ceases the stimulation once glucose returns to normal. Therefore, when used as a monotherapy, the risk of severe hypoglycemia (low blood sugar) is significantly lower compared to some classic diabetes medications.
An important distinction must also be noted: A higher-dose version of the same active ingredient (semaglutide), approved specifically for obesity treatment, is known as Wegovy. Ozempic, on the other hand, officially holds a primary indication for Type 2 diabetes.
What is the Difference with Mounjaro (Tirzepatide)? A Dual-Action Revolution
Tirzepatide, the active ingredient in Mounjaro, is one of the most significant innovations in this field; because it is the world's first and currently best-known dual incretin agonist. While semaglutide exclusively activates the GLP-1 receptor, Tirzepatide simultaneously stimulates both the GLP-1 and GIP receptors.
Unlocking both incretin pathways simultaneously translates to a more potent effect in both glycemic control and weight loss—especially at higher doses—for most patients. The addition of the GIP axis is thought to complement the effects of GLP-1 by contributing to insulin sensitivity and adipose tissue metabolism. In practice, this means greater weight loss and more pronounced reductions in HbA1c (three-month average blood glucose) are observed with Tirzepatide compared to Semaglutide in many patients.
However, "more potent" does not always mean "better for everyone"; gastrointestinal side effects such as nausea, vomiting, and diarrhea during dose escalations are a reality that must be managed.
Are the Benefits of These Drugs Limited to Blood Sugar and Weight?
No, and this is the most exciting development of recent years. The impacts of these medications extend beyond metabolic boundaries. In a comprehensive real-world analysis encompassing nearly one million patients published in the journal Nature Medicine in 2025, both Tirzepatide and Semaglutide were shown to reduce the risk of heart attacks, stroke, and overall mortality.
A striking finding is that these protective effects emerge in the early stages of treatment; this suggests that the benefit is not solely dependent on weight loss, but that the drugs may have direct protective effects on the cardiovascular system. Furthermore, Semaglutide has also received an indication for reducing the risk of kidney disease progression in individuals with Type 2 diabetes and chronic kidney disease. Additionally, new administration methods, such as the oral tablet form of Semaglutide (Rybelsus), are expanding options for patients with a fear of needles.
The Situation in Turkey and Important Warnings:
In Turkey, these medications, whose active ingredients are Semaglutide (Ozempic) and Tirzepatide (Mounjaro), are approved by the Ministry of Health for the treatment of Type 2 diabetes and are available by prescription. Procuring and using them strictly for weight loss purposes without medical supervision and a proper indication is incorrect and risky.
These medications are not miracles, but rather serious medical treatments. Potential side effects and conditions requiring caution include:
- Frequently observed gastrointestinal complaints: nausea, vomiting, diarrhea, or constipation (especially during dose escalation periods).
- Rare but serious: risk of pancreatic inflammation (pancreatitis).
- They should not be used in individuals with a specific history of thyroid cancer (especially medullary thyroid carcinoma) or Multiple Endocrine Neoplasia type 2 (MEN-2) syndrome.
- Aesthetic consequences such as muscle loss and facial hollowing ("Ozempic face") due to rapid weight loss; therefore, adequate protein intake and supervision by a physician or dietitian are important.
For this reason, medication selection, dosing, and follow-up must absolutely be conducted by an endocrinology or internal medicine specialist; after evaluating thyroid, pancreatic, and renal functions.
A Candidate on the Horizon: “Viking Therapeutics” and VK2735
This field is rapidly evolving, and one closely monitored candidate is the "VK2735" molecule developed by the US-based Viking Therapeutics. VK2735, much like Mounjaro (Tirzepatide), is a dual agonist that stimulates both the GLP-1 and GIP receptors; meaning it operates on the aforementioned principle of "unlocking two Incretin pathways simultaneously.”
What makes it particularly noteworthy is its development in two separate formats: a once-weekly "injection (subcutaneous)" formulation and a once-daily "oral tablet" formulation. An oral dual-action medication option for patients reluctant to use injections holds significant potential for convenience within this class. In Phase 2 trials, the injectable form reported up to 15% weight loss from baseline at 13 weeks, while the oral form reported up to 12% weight loss, also at 13 weeks; these are promising results for an early stage.
However, a very critical caveat must be emphasized here: VK2735 is not yet an approved medication. Currently, large-scale Phase 3 trials (the VANQUISH program) are ongoing, and it is not available as a prescription treatment option in pharmacies. The reported weight loss percentages are preliminary findings derived from small, short-term early-phase studies; they cannot yet be compared to the extensive, long-term safety data that exists for Ozempic and Mounjaro. If Phase 3 results are favorable and regulatory authorities grant approval, it is projected that market entry would only be possible in the coming years. In short, VK2735 is an exciting development to watch as a potential option for the near future, not for today.
The Importance of Expert Opinion for the Right Decision
Incretin-based medications, such as Ozempic and Mounjaro, have created a genuine paradigm shift in the treatment of diabetes and obesity. Their ability to restrain the liver by silencing Glucagon, regulate appetite, and, according to recent data, offer cardiovascular protection, makes them highly valuable tools.
However, it must not be forgotten: No medication can substitute for a healthy diet, regular physical activity, and proper medical follow-up. Determining which medication is appropriate for which patient, and at what dose, is a multidisciplinary decision that varies according to comorbidities, laboratory results, and personal goals. A holistic approach, evaluated collaboratively by endocrinology, internal medicine, and nutrition experts, both increases the success of the treatment and minimizes the risks of side effects.
At eKonsey, we believe in the importance of making critical health decisions collaboratively with a council of specialized physicians, rather than relying on a single opinion.
Frequently Asked Questions
- Are Ozempic and Mounjaro GLP-1 blockers? No. These medications do not block the GLP-1 receptor; they activate it. Their correct designation is GLP-1 receptor agonists. Because Mounjaro also activates the GIP receptor, it is classified as a dual agonist.
- What is the main difference between Ozempic and Mounjaro? Ozempic (Semaglutide) solely stimulates the GLP-1 pathway. Mounjaro (Tirzepatide) stimulates both the GLP-1 and GIP pathways simultaneously, providing more potent weight loss and glycemic control in most patients.
- How do these drugs lower blood sugar? In three ways: by increasing insulin secretion (when glucose is high), by suppressing Glucagon to curb the liver's excessive glucose production, and by delaying gastric emptying.
- Do these drugs cause hypoglycemia (low blood sugar)? When used alone, the risk of severe hypoglycemia is low; because their insulin-stimulating effects are glucose-dependent. However, the risk may increase when used in combination with medications like insulin or sulfonylureas.
- I do not have diabetes, can I use them just to lose weight? You should not make this decision on your own. The use of these potent medications requires indication and physician evaluation. Unprescribed or unmonitored use carries serious risks.
We wish you healthy days.
Dr. Jan Klod Kayuka
Internal Medicine