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Medically reviewed by Fedorchenko Olga Valeryevna, PharmD. Last updated on 27.04.2022
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Sitagliptin (Istamet) PHOSPHATE + Metformin (Istamet) HCl (Istamet) are indicated as initial therapy in patients with type 2 diabetes mellitus to improve glycemic control when diet and exercise do not provide adequate glycemic control.
Sitagliptin (Istamet) PHOSPHATE + Metformin (Istamet) HCl (Istamet) are indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus inadequately controlled on Metformin (Istamet) or Sitagliptin (Istamet) alone or in patients already being treated with the combination of Sitagliptin (Istamet) and Metformin (Istamet).
Sitagliptin (Istamet) PHOSPHATE + Metformin (Istamet) HCl (Istamet) are indicated as part of triple combination therapy with a sulfonylurea as an adjunct to diet and exercise in patients with type 2 diabetes mellitus inadequately controlled with any two of the three agents: Metformin (Istamet), Sitagliptin (Istamet), or a sulfonylurea.
Sitagliptin (Istamet) PHOSPHATE + Metformin (Istamet) HCl (Istamet) are indicated as part of triple combination therapy with a PPARγ agonist (i.e., thiazolidinediones) as an adjunct to diet and exercise in patients with type 2 diabetes mellitus inadequately controlled with any two of the three agents: Metformin (Istamet), Sitagliptin (Istamet), or a PPARγ agonist.
Sitagliptin (Istamet) PHOSPHATE + Metformin (Istamet) HCl (Istamet) are indicated in patients with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control in combination with insulin.
Metformin (Istamet) and Sitagliptin (Istamet) are oral diabetes medicines that help control blood sugar levels.
Metformin (Istamet) works by decreasing glucose (sugar) production in the liver and decreasing absorption of glucose by the intestines. Sitagliptin (Istamet) works by regulating the levels of insulin your body produces after eating.
Istamet (Istamet) is a combination medicine used to treat type 2 diabetes. This medication is not for treating type 1 diabetes.
Istamet (Istamet) may also be used for purposes not listed in this medication guide.
Recommended Dosing
The dose of Istamet should be individualized on the basis of the patient's current regimen, effectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100 mg Sitagliptin (Istamet) and 2000 mg Metformin (Istamet). Initial combination therapy or maintenance of combination therapy should be individualized and left to the discretion of the healthcare provider.
- In patients not currently treated with Metformin (Istamet), the recommended total daily starting dose of Istamet is 100 mg Sitagliptin (Istamet) and 1000 mg Metformin (Istamet) hydrochloride (HCl) extended-release. Patients with inadequate glycemic control on this dose of Metformin (Istamet) can be titrated gradually, to reduce gastrointestinal side effects associated with Metformin (Istamet), up to the maximum recommended daily dose.
- In patients already treated with Metformin (Istamet), the recommended total daily starting dose of Istamet is 100 mg Sitagliptin (Istamet) and the previously prescribed dose of Metformin (Istamet).
- For patients taking Metformin (Istamet) immediate-release 850 mg twice daily or 1000 mg twice daily, the recommended starting dose of Istamet is two 50 mg Sitagliptin (Istamet)/1000 mg Metformin (Istamet) hydrochloride extended-release tablets taken together once daily.
- Maintain the same total daily dose of Sitagliptin (Istamet) and Metformin (Istamet) when changing between Istamet (Sitagliptin (Istamet) and Metformin (Istamet) HCl immediate-release) and Istamet. Patients with inadequate glycemic control on this dose of Metformin (Istamet) can be titrated gradually, to reduce gastrointestinal side effects associated with Metformin (Istamet), up to the maximum recommended daily dose.
Istamet should be administered with food to reduce the gastrointestinal side effects associated with the Metformin (Istamet) component. Istamet should be given once daily with a meal preferably in the evening. Istamet should be swallowed whole. The tablets must not be split, crushed, or chewed before swallowing. There have been reports of incompletely dissolved Istamet tablets being eliminated in the feces. It is not known whether this material seen in feces contains active drug. If a patient reports repeatedly seeing tablets in feces, the healthcare provider should assess adequacy of glycemic control.
The 100 mg Sitagliptin (Istamet)/1000 mg Metformin (Istamet) hydrochloride extended-release tablet should be taken as a single tablet once daily. Patients using two Istamet tablets (such as two 50 mg Sitagliptin (Istamet)/500 mg Metformin (Istamet) hydrochloride extended-release tablets or two 50 mg Sitagliptin (Istamet)/1000 mg Metformin (Istamet) hydrochloride extended-release tablets) should take the two tablets together once daily.
Patients treated with an insulin secretagogue or insulin
Coadministration of Istamet with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower doses of the insulin secretagogue or insulin to reduce the risk of hypoglycemia.
No studies have been performed specifically examining the safety and efficacy of Istamet in patients previously treated with other oral antihyperglycemic agents and switched to Istamet. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring as changes in glycemic control can occur.
See also:
What is the most important information I should know about Istamet?
Known hypersensitivity to Sitagliptin (Istamet) phosphate, Metformin (Istamet) HCl or any other component of Istamet.
Renal disease or renal dysfunction, eg, as suggested by serum creatinine levels ≥1.5 mg/dL [males], ≥1.4 mg/dL [females], or abnormal creatinine clearance, which may also result from conditions eg, cardiovascular collapse (shock), acute myocardial infarction, and septicemia.
Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.
Istamet should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because the use of such products may result in acute alteration of renal function.
Use in lactation: No studies in lactating animals have been conducted with the combined components of Istamet. In studies performed with the individual components, both Sitagliptin (Istamet) and Metformin (Istamet) are secreted in the milk of lactating rats. It is not known whether Sitagliptin (Istamet) is excreted in human milk. Therefore, Istamet should not be used by a woman who is nursing.
Use Istamet as directed by your doctor. Check the label on the medicine for exact dosing instructions.
- Istamet comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Istamet refilled.
- Take Istamet by mouth with your evening meal, unless your doctor tells you otherwise.
- Swallow Istamet whole. Do not break, crush, split, or chew before swallowing. If you have difficulty swallowing tablets whole, talk with your doctor.
- Taking Istamet at the same times each day will help you remember to take it.
- Take Istamet on a regular schedule to get the most benefit from it.
- Continue to take Istamet even if you feel well. Do not miss any doses.
- If you miss a dose of Istamet, take it with food as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.
Ask your health care provider any questions you may have about how to use Istamet.
There are specific as well as general uses of a drug or medicine. A medicine can be used to prevent a disease, treat a disease over a period or cure a disease. It can also be used to treat the particular symptom of the disease. The drug use depends on the form the patient takes it. It may be more useful in injection form or sometimes in tablet form. The drug can be used for a single troubling symptom or a life-threatening condition. While some medications can be stopped after few days, some drugs need to be continued for prolonged period to get the benefit from it.Sitagliptin (Istamet)/Metformin (Istamet) is used with a proper diet and exercise program to control high blood sugar in people with type 2 diabetes. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems. Proper control of diabetes may also lessen your risk of a heart attack or stroke.
This product contains 2 medications: Sitagliptin (Istamet) and Metformin (Istamet). Sitagliptin (Istamet) works by increasing levels of natural substances called incretins. Incretins help to control blood sugar by increasing insulin release, especially after a meal. They also decrease the amount of sugar your liver makes. Metformin (Istamet) works by helping to restore your body's proper response to the insulin you naturally produce. It also decreases the amount of sugar that your liver makes and that your stomach/intestines absorb.
How to use Istamet
Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start using Sitagliptin (Istamet)/Metformin (Istamet) and each time you get a refill. If you have any questions, ask your doctor or pharmacist.
Take this medication by mouth as directed by your doctor, usually once daily with a meal, preferably in the evening. Do not crush or chew extended-release tablets. Doing so can release all of the drug at once, increasing the risk of side effects. Also, do not split the tablets unless they have a score line and your doctor or pharmacist tells you to do so. Swallow the whole or split tablet without crushing or chewing. Drink plenty of fluids while taking this medication unless otherwise directed by your doctor.
The dosage is based on your medical condition, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). To reduce your risk of side effects (such as upset stomach), your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully.
Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day. Carefully follow the medication treatment plan, meal plan, and exercise program your doctor has recommended.
Tell your doctor if your condition does not improve or if it worsens (your blood sugar levels are too high or too low).
See also:
What other drugs will affect Istamet?
Carbonic Anhydrase Inhibitors
Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs may induce metabolic acidosis. Use these drugs with caution in patients treated with Istamet, as the risk of lactic acidosis may increase.
Cationic Drugs
Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with Metformin (Istamet) by competing for common renal tubular transport systems. Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of Istamet and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system.
The Use of Metformin (Istamet) with Other Drugs
Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving Istamet the patient should be closely observed to maintain adequate glycemic control.
See also:
What are the possible side effects of Istamet?
Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Sitagliptin (Istamet) and Metformin (Istamet) Co-Administration in Patients with Type 2 Diabetes Inadequately Controlled on Diet and Exercise: Table 6 summarizes the most common (≥5% of patients) adverse reactions reported (regardless of investigator assessment of causality) in a 24-week placebo-controlled factorial study in which Sitagliptin (Istamet) and Metformin (Istamet) were co-administered to patients with type 2 diabetes inadequately controlled on diet and exercise.
Sitagliptin (Istamet) Add-On Therapy in Patients with Type 2 Diabetes Inadequately Controlled on Metformin (Istamet) Alone: In a 24-week placebo-controlled trial of Sitagliptin (Istamet) 100 mg administered once daily added to a twice daily Metformin (Istamet) regimen, there were no adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients and more commonly than in patients given placebo. Discontinuation of therapy due to clinical adverse reactions was similar to the placebo treatment group (Sitagliptin (Istamet) and Metformin (Istamet), 1.9%; placebo and Metformin (Istamet), 2.5%).
Gastrointestinal Adverse Reactions: The incidences of pre-selected gastrointestinal adverse experiences in patients treated with Sitagliptin (Istamet) and Metformin (Istamet) were similar to those reported for patients treated with Metformin (Istamet) alone.
Sitagliptin (Istamet) in Combination with Metformin (Istamet) and Glimepiride: In a 24-week placebo-controlled study of Sitagliptin (Istamet) 100 mg as add-on therapy in patients with type 2 diabetes inadequately controlled on Metformin (Istamet) and glimepiride (Sitagliptin (Istamet), n=116; placebo, n=113), the adverse reactions reported regardless of investigator assessment of causality in ≥5% of patients treated with Sitagliptin (Istamet) and more commonly than in patients treated with placebo were: Hypoglycemia and headache (6.9%, 2.7%).
Sitagliptin (Istamet) in Combination with Metformin (Istamet) and Insulin: In a 24-week placebo-controlled study of Sitagliptin (Istamet) 100 mg as add-on therapy in patients with type 2 diabetes inadequately controlled on Metformin (Istamet) and insulin (Sitagliptin (Istamet), N=229; placebo, N=233), the only adverse reaction reported regardless of investigator assessment of causality in ≥5% of patients treated with Sitagliptin (Istamet) and more commonly than in patients treated with placebo was hypoglycemia (Table 8).
Hypoglycemia: In all (N=5) studies, adverse reactions of hypoglycemia were based on all reports of symptomatic hypoglycemia; a concurrent glucose measurement was not required although most (77%) reports of hypoglycemia were accompanied by a blood glucose measurement ≤70 mg/dL. When the combination of Sitagliptin (Istamet) and Metformin (Istamet) was co-administered with a sulfonylurea or with insulin, the percentage of patients reporting at least 1 adverse reaction of hypoglycemia was higher than that observed with placebo and Metformin (Istamet) co-administered with a sulfonylurea or with insulin (Table 8).
The overall incidence of reported adverse reactions of hypoglycemia in patients with type 2 diabetes inadequately controlled on diet and exercise was 0.6% in patients given placebo, 0.6% in patients given Sitagliptin (Istamet) alone, 0.8% in patients given Metformin (Istamet) alone, and 1.6% in patients given Sitagliptin (Istamet) in combination with Metformin (Istamet). In patients with type 2 diabetes inadequately controlled on Metformin (Istamet) alone, the overall incidence of adverse reactions of hypoglycemia was 1.3% in patients given add-on Sitagliptin (Istamet) and 2.1% in patients given add-on placebo.
With the combination of Sitagliptin (Istamet) and Metformin (Istamet), no clinically meaningful changes in vital signs or in ECG (including in QTc interval) were observed.
The most common adverse experience in Sitagliptin (Istamet) monotherapy reported regardless of investigator assessment of causality in ≥5% of patients and more commonly than in patients given placebo was nasopharyngitis.
The most common (>5%) established adverse reactions due to initiation of Metformin (Istamet) therapy are diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia and headache.
Laboratory Tests: Sitagliptin (Istamet): The incidence of laboratory adverse reactions was similar in patients treated with Sitagliptin (Istamet) and Metformin (Istamet) (7.6%) compared to patients treated with placebo and Metformin (Istamet) (8.7%). In most but not all studies, a small increase in white blood cell count (approximately 200 cells/microliter difference in WBC vs placebo, mean baseline WBC approximately 6600 cells/microliter) was observed due to a small increase in neutrophils. This change in laboratory parameters is not considered to be clinically relevant.
Metformin (Istamet) HCl: In controlled clinical trials of Metformin (Istamet) of 29 weeks duration, a decrease to subnormal levels of previously normal serum vitamin B12 levels, without clinical manifestations, was observed in approximately 7% of patients. Such decrease, possibly due to interference with vitamin B12 absorption from the B12-intrinsic factor complex is however, very rarely associated with anemia and appears to be rapidly reversible with discontinuation of Metformin (Istamet) or vitamin B12 supplementation.
Post-Marketing Experience: Additional adverse reactions have been identified during post-approval of Istamet or Sitagliptin (Istamet), 1 of the components of Istamet. These reactions have been reported when Istamet or Sitagliptin (Istamet) have been used alone and/or in combination with other antihyperglycemic agents. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypersensitivity reactions, including anaphylaxis, angioedema, rash, urticaria, cutaneous vasculitis and exfoliative skin conditions, including Stevens-Johnson syndrome, upper respiratory tract infection; hepatic enzyme elevations; acute pancreatitis, including fatal and nonfatal hemorrhagic and necrotizing pancreatitis; worsening renal function, including acute renal failure (sometimes requiring dialysis); constipation; vomiting; headache; arthralgia; myalgia; pain in extremity; back pain.
Each film-coated tablet contains Sitagliptin (Istamet) phosphate monohydrate 64.25 mg and Metformin (Istamet) HCl equivalent to: Sitagliptin (Istamet) 50 mg as free base and Metformin (Istamet) HCl 500 mg (Istamet 50/500 mg), Metformin (Istamet) HCl 850 mg (Istamet 50/850 mg) or Metformin (Istamet) HCl 1000 mg (Istamet 50/1000 mg).
It also contains the following inactive ingredients: Microcrystalline cellulose, polyvinylpyrrolidone, sodium lauryl sulfate and sodium stearyl fumarate. In addition, the film coating contains the following inactive ingredients: Polyvinyl alcohol, polyethylene glycol, talc, titanium dioxide, red iron oxide and black iron oxide.
Istamet contains 2 oral antihyperglycemic drugs used in the management of type 2 diabetes: Sitagliptin (Istamet) phosphate and Metformin (Istamet) HCl.
Sitagliptin (Istamet) phosphate is an orally-active inhibitor of the dipeptidyl peptidase-4 (DDP-4) enzyme. Sitagliptin (Istamet) is present in Istamet in the form of Sitagliptin (Istamet) phosphate monohydrate. Sitagliptin (Istamet) phosphate monohydrate is 7-[(3R)-3-amino-1-oxo-4-(2, 4, 5-trifluorophenyl)butyl]-5, 6, 7, 8-tetrahydro-3-(trifluoromethyl)-1, 2, 4-triazolo[4, 3-a]pyrazine phosphate (1:1) monohydrate with an empirical formula of C16H15F6N5O·H3PO4·H2O and a molecular weight of 523.32.
Sitagliptin (Istamet) phosphate monohydrate is a white to off-white, crystalline, nonhygroscopic powder. It is soluble in water and N, N-dimethyl formamide; slightly soluble in methanol; very slightly soluble in ethanol, acetone and acetonitrile; and insoluble in isopropanol and isopropyl acetate.
Metformin (Istamet) HCl (N, N-dimethylimidodicarbonimidic diamide hydrochloride) is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents. Metformin (Istamet) HCl is a white to off-white crystalline compound with a molecular formula of C4H11N5·HCl and a molecular weight of 165.63. Metformin (Istamet) HCl is freely soluble in water and is practically insoluble in acetone, ether and chloroform. The pKa of Metformin (Istamet) is 12.4. The pH of a 1% aqueous solution of Metformin (Istamet) HCl is 6.68.