Ermegisto (Sitagliptin/Dapagliflozin)

What Is Ermegisto and What Is It Used For?

Ermegisto is a prescription combination tablet containing sitagliptin 100 mg and dapagliflozin 10 mg, used to improve blood sugar control in adults with type 2 diabetes mellitus. It combines two different classes of antidiabetic drugs – a DPP-4 inhibitor and an SGLT2 inhibitor – that work through complementary mechanisms to lower blood glucose levels.

Type 2 diabetes mellitus is a chronic metabolic condition affecting over 500 million people worldwide, according to the International Diabetes Federation. It occurs when the body becomes resistant to insulin or when the pancreas cannot produce enough insulin to maintain normal blood glucose levels. Over time, poorly controlled blood sugar leads to serious complications including cardiovascular disease, kidney damage, nerve damage, and vision loss.

Ermegisto addresses this challenge by combining two well-established active ingredients in a single tablet. Sitagliptin belongs to the dipeptidyl peptidase-4 (DPP-4) inhibitor class. It works by blocking the enzyme DPP-4, which normally breaks down incretin hormones (GLP-1 and GIP). By preserving these hormones, sitagliptin enhances insulin secretion in response to meals and reduces the release of glucagon, a hormone that raises blood sugar. Importantly, this mechanism is glucose-dependent, meaning it primarily acts when blood sugar is elevated, reducing the risk of hypoglycemia.

Dapagliflozin belongs to the sodium-glucose co-transporter 2 (SGLT2) inhibitor class. It works in the kidneys by blocking the SGLT2 protein responsible for reabsorbing approximately 90% of filtered glucose back into the bloodstream. By inhibiting this transporter, dapagliflozin causes excess glucose to be excreted in the urine, lowering blood sugar levels through an insulin-independent mechanism. This results in a caloric loss of approximately 200–300 kilocalories per day, contributing to modest weight reduction.

The combination of these two mechanisms provides several advantages. Both drugs lower HbA1c (a marker of long-term blood sugar control) through independent pathways, and clinical evidence suggests their effects are additive. Patients who do not achieve adequate glycemic control with either drug alone, or who are already taking both drugs as separate tablets, may benefit from the convenience and efficacy of a fixed-dose combination.

Indications and approved uses

Ermegisto is indicated for the treatment of type 2 diabetes mellitus in adults to improve glycemic control when treatment with both sitagliptin and dapagliflozin is appropriate. It may be used:

• As a replacement for patients already taking sitagliptin and dapagliflozin as separate tablets
• In combination with metformin when metformin alone does not provide adequate blood sugar control
• In combination with other antidiabetic agents (including insulin) when the existing regimen does not provide sufficient glycemic control
• Alongside diet and exercise modifications as part of a comprehensive diabetes management plan

How the dual mechanism differs from monotherapy

Using sitagliptin and dapagliflozin together targets two fundamentally different physiological pathways. The DPP-4 inhibitor component enhances the gut-pancreas axis by boosting incretin hormones, while the SGLT2 inhibitor component acts on the kidneys to promote glucose excretion. Because these mechanisms do not overlap, the blood-sugar-lowering effects are complementary. Clinical studies of SGLT2 inhibitors combined with DPP-4 inhibitors have demonstrated additional HbA1c reductions of 0.4–0.7% compared with either class alone.

What Should You Know Before Taking Ermegisto?

Before starting Ermegisto, inform your doctor about your complete medical history, especially any kidney problems, history of pancreatitis, urinary tract infections, low blood pressure, or dehydration. Ermegisto is not recommended during pregnancy or breastfeeding. Your doctor will check your kidney function before prescribing this medication.

As with any prescription medication, there are important considerations to discuss with your healthcare provider before beginning treatment with Ermegisto. Because this is a combination product, the precautions and contraindications of both sitagliptin and dapagliflozin apply.

Contraindications

Ermegisto must not be used in the following situations:

• Hypersensitivity: Known allergy to sitagliptin, dapagliflozin, or any of the excipients in the tablet. Serious hypersensitivity reactions including anaphylaxis, angioedema, and severe cutaneous reactions have been reported with sitagliptin
• Type 1 diabetes: Ermegisto is not indicated for type 1 diabetes mellitus and should never be used as a substitute for insulin in insulin-dependent patients
• Diabetic ketoacidosis (DKA): Active or a history of diabetic ketoacidosis is a contraindication. SGLT2 inhibitors have been associated with rare cases of euglycemic DKA
• Severe renal impairment: Ermegisto should not be initiated in patients with an estimated glomerular filtration rate (eGFR) below 25 mL/min/1.73 m², as the glucose-lowering efficacy of dapagliflozin is reduced in severe kidney disease

Warnings and precautions

Several important warnings and precautions should be considered when taking Ermegisto. Healthcare providers should carefully evaluate the risk-benefit profile for each patient.

Pancreatitis: Cases of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, have been reported in patients taking DPP-4 inhibitors including sitagliptin. Patients should be informed of the characteristic symptom of acute pancreatitis – persistent severe abdominal pain that may radiate to the back. If pancreatitis is suspected, Ermegisto should be discontinued immediately and appropriate management initiated.

Diabetic ketoacidosis (DKA): Rare cases of DKA, including life-threatening events, have been reported in patients with type 2 diabetes treated with SGLT2 inhibitors. In some cases, blood glucose levels were only moderately elevated (euglycemic DKA). Patients should be assessed for ketoacidosis if they present with nausea, vomiting, abdominal pain, fatigue, or difficulty breathing, even if blood glucose levels are not significantly elevated.

Volume depletion: Dapagliflozin causes osmotic diuresis, which can lead to intravascular volume contraction and hypotension. Patients at risk include elderly patients, those on loop diuretics, and those with low blood pressure. Adequate hydration is recommended, and volume status should be assessed before initiating treatment.

Genital and urinary tract infections: SGLT2 inhibitors increase glucose concentration in the urine, creating an environment that favors the growth of bacteria and yeast. Genital mycotic infections (thrush) and urinary tract infections occur more frequently with dapagliflozin. Patients with a history of recurrent infections should be monitored carefully.

Necrotizing fasciitis of the perineum (Fournier’s gangrene): Rare but serious cases of necrotizing fasciitis of the perineum have been reported with SGLT2 inhibitors. Patients should seek immediate medical attention if they experience pain, tenderness, redness, or swelling of the genital or perineal area, accompanied by fever or malaise.

Pregnancy and breastfeeding

Ermegisto is not recommended during pregnancy. There are limited data on the use of sitagliptin and dapagliflozin in pregnant women. Animal studies with dapagliflozin have shown adverse effects on kidney development in the fetus, particularly during the second and third trimesters. Women of childbearing age should use effective contraception during treatment. If pregnancy is planned or confirmed, Ermegisto should be discontinued and an alternative diabetes treatment initiated.

Ermegisto should not be used during breastfeeding. Dapagliflozin and its metabolites are excreted in human milk. Because of the potential for adverse effects on the nursing infant, particularly on kidney maturation, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the medication to the mother.

How Does Ermegisto Interact with Other Drugs?

Ermegisto can interact with insulin and sulfonylureas (increasing hypoglycemia risk), loop diuretics (increasing dehydration risk), and certain other medications. Always inform your healthcare provider about all medicines you are taking, including over-the-counter drugs and supplements.

Drug interactions with Ermegisto are based on the known interaction profiles of its two active ingredients, sitagliptin and dapagliflozin. While neither drug is extensively metabolized by cytochrome P450 enzymes (reducing the risk of many common pharmacokinetic interactions), several clinically important interactions exist that require awareness and possible dose adjustments.

Sitagliptin is primarily eliminated unchanged by the kidneys and is a minor substrate of CYP3A4 and CYP2C8. Dapagliflozin is primarily metabolized by UGT1A9 (a glucuronidation enzyme) and has limited interaction potential through CYP pathways. Despite this relatively favorable profile, the pharmacodynamic interactions – especially those affecting blood sugar levels and fluid balance – are clinically significant.

Major interactions

Minor interactions and considerations

Patients should always provide their healthcare provider with a complete list of all current medications, including over-the-counter drugs, vitamins, herbal supplements, and recreational substances. While Ermegisto has a relatively favorable drug interaction profile, the combination of multiple antidiabetic agents requires careful monitoring to prevent hypoglycemia and other adverse events.

What Is the Correct Dosage of Ermegisto?

The standard dose of Ermegisto is one tablet (sitagliptin 100 mg/dapagliflozin 10 mg) taken once daily, with or without food. The tablet should be swallowed whole and not crushed, split, or chewed. Kidney function must be checked before starting treatment.

Ermegisto is available as a fixed-dose combination film-coated tablet containing sitagliptin 100 mg and dapagliflozin 10 mg. The dosing regimen is straightforward, but individual patient factors – particularly kidney function – must be considered before and during treatment.

Adults

The recommended dose is one tablet taken once daily. Ermegisto can be taken at any time of day with or without food, although consistent timing is recommended to help maintain a steady routine. Patients transitioning from separate sitagliptin and dapagliflozin tablets can switch directly to the combination tablet at the same dose they were previously taking.

Children

Elderly

Renal impairment

Missed dose

If you miss a dose of Ermegisto, take it as soon as you remember on the same day. If the missed dose is remembered close to the time of the next dose, skip the missed dose and take the next dose at the regular time. Do not take a double dose to make up for the forgotten one. Taking two tablets in one day increases the risk of side effects, including hypoglycemia and dehydration.

Overdose

In the event of an overdose, standard supportive measures should be taken. Sitagliptin is modestly dialyzable (approximately 13.5% removed over a 3–4 hour hemodialysis session). Dapagliflozin is unlikely to be significantly removed by hemodialysis due to its protein binding. There is no specific antidote for an overdose of either component. Symptoms may include excessive glucose excretion, dehydration, and low blood sugar (especially if combined with other antidiabetic drugs). Contact your local poison control center or seek emergency medical attention immediately in case of suspected overdose.

What Are the Side Effects of Ermegisto?

The most common side effects of Ermegisto include genital yeast infections, urinary tract infections, increased urination, nasopharyngitis, and headache. Most side effects are mild to moderate and related to the SGLT2 inhibitor component (dapagliflozin). Serious but rare side effects include diabetic ketoacidosis, pancreatitis, and severe allergic reactions.

The side effect profile of Ermegisto reflects the combined safety data of its two active ingredients, sitagliptin and dapagliflozin, each of which has been extensively studied in large clinical trials involving thousands of patients. Understanding the frequency and nature of potential side effects helps patients and healthcare providers make informed treatment decisions.

The side effects are classified according to their frequency of occurrence. It is important to note that many patients tolerate Ermegisto well, and not everyone will experience side effects. The benefits of improved blood sugar control must be weighed against the risk of adverse events on an individual basis.

Most side effects related to the dapagliflozin component (genital infections, increased urination) are a direct consequence of the drug’s mechanism of action – excess glucose in the urine creates a favorable environment for yeast and bacteria, while the osmotic diuretic effect increases urine volume. Good genital hygiene and adequate fluid intake can help minimize these effects.

Sitagliptin-related side effects are generally mild. The most notable rare risks include pancreatitis and severe hypersensitivity reactions. Patients should be counseled to report any persistent severe abdominal pain, as this may indicate acute pancreatitis.

How Should You Store Ermegisto?

Store Ermegisto at room temperature below 30°C (86°F) in the original packaging to protect from moisture. Keep out of reach of children. Do not use after the expiration date on the package.

Proper storage of medications is essential to maintain their effectiveness and safety. Ermegisto film-coated tablets should be stored under the following conditions:

• Temperature: Store below 30°C (86°F). Do not refrigerate or freeze
• Moisture protection: Keep the tablets in their original blister packaging until use. The packaging is designed to protect against moisture, which can degrade the active ingredients
• Light protection: Store in the original carton to protect from light if so indicated on the packaging
• Child safety: Keep out of sight and reach of children. Consider storing in a locked medicine cabinet
• Expiration date: Do not use Ermegisto after the expiry date printed on the blister and outer carton. The expiry date refers to the last day of that month

Do not dispose of medications via household waste or wastewater. Ask your pharmacist how to dispose of medications you no longer use. These measures help to protect the environment and prevent accidental exposure.

If you notice any change in the appearance of the tablets (discoloration, chipping, unusual odor), do not take the medication and consult your pharmacist. Film-coated tablets that appear damaged may have reduced potency or altered release characteristics.

What Does Ermegisto Contain?

Each Ermegisto tablet contains two active ingredients: sitagliptin 100 mg (as sitagliptin phosphate monohydrate) and dapagliflozin 10 mg (as dapagliflozin propanediol monohydrate). The tablet also contains excipients including microcrystalline cellulose, calcium hydrogen phosphate, and a film-coating.

Active ingredients

Each film-coated tablet of Ermegisto contains:

• Sitagliptin 100 mg (as sitagliptin phosphate monohydrate) – a selective DPP-4 inhibitor. Sitagliptin is a white to off-white crystalline powder with the molecular formula C₁₆H₁₅F₆N₅O·H₃PO₄·H₂O
• Dapagliflozin 10 mg (as dapagliflozin propanediol monohydrate) – a selective, reversible SGLT2 inhibitor. Dapagliflozin is a C-aryl glucoside with the molecular formula C₂₁H₂₅ClO₆·C₃H₈O₂·H₂O

Inactive ingredients (excipients)

The tablet core and film coating contain excipients that are standard in pharmaceutical manufacturing. These typically include:

• Microcrystalline cellulose (tablet filler and binder)
• Calcium hydrogen phosphate (dibasic, anhydrous) (tablet filler)
• Croscarmellose sodium (disintegrant for tablet dissolution)
• Magnesium stearate (lubricant for manufacturing)
• Sodium stearyl fumarate (lubricant)
• Film-coating: polyvinyl alcohol, titanium dioxide (E171), macrogol/PEG, talc, iron oxide pigments

Patients with known hypersensitivity or intolerance to any of the excipients should inform their healthcare provider before starting treatment. The film-coated tablet formulation is designed for ease of swallowing and to protect the active ingredients from degradation in the stomach.