Janumet

Primary Use

Janumet is used to manage blood glucose (sugar) levels in adults with type 2 diabetes mellitus. It contains two active ingredients, sitagliptin and metformin, which work in different ways to help the body lower blood sugar.

Treatment Integration

This medication is intended for use as part of a comprehensive treatment plan that includes a specific diet and physical activity. Healthcare providers may prescribe Janumet when diet and exercise alone are not enough to control blood sugar levels, or for patients who are already taking both sitagliptin and metformin as separate tablets.

Controlling high blood sugar is essential for preventing serious health complications, including:

• Kidney damage
• Nerve problems
• Loss of limbs
• Vision issues

Limitations of Use

Janumet is not used to treat type 1 diabetes, a condition where the body does not produce insulin. It is also not intended for the treatment of diabetic ketoacidosis, which is a serious complication of diabetes involving high levels of ketones in the blood or urine.

How Janumet Works

Janumet contains two active ingredients, sitagliptin and metformin, which target blood sugar control through different mechanisms in the body.

Sitagliptin

Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor. It works by increasing the levels of natural substances called incretin hormones. These hormones help regulate blood sugar by:

• Signaling the pancreas to release more insulin, especially after a meal.
• Signaling the liver to stop producing excess sugar when it is not needed.

Metformin

Metformin belongs to a class of drugs called biguanides. It helps lower blood sugar levels in three primary ways:

• Reducing liver production: It decreases the amount of glucose (sugar) that the liver produces.
• Decreasing absorption: It reduces the amount of sugar the intestines absorb from the diet.
• Improving insulin sensitivity: It helps the body respond better to its own natural insulin, allowing cells to use glucose more effectively.

By combining these two actions, Janumet helps manage blood sugar levels throughout the day and after eating.

Common Side Effects

The most frequently reported side effects of Janumet involve the digestive system and the upper respiratory tract. These may include:

• Diarrhea, nausea, and gas
• Stomach upset or abdominal pain
• Headache
• Stuffy or runny nose and sore throat

Serious Side Effects

While less common, some side effects can be severe. Seek medical attention immediately if you experience any of the following:

• Pancreatitis: Severe and persistent pain in the abdomen that may spread to the back, with or without vomiting.
• Lactic Acidosis: A rare but dangerous buildup of lactic acid. Symptoms include unusual tiredness, muscle pain, trouble breathing, feeling cold, or a slow or irregular heartbeat.
• Heart Failure: Symptoms include increasing shortness of breath, swelling in the feet or legs, and sudden weight gain.
• Kidney Problems: Changes in urination or swelling in the lower body.
• Severe Joint Pain: Intense or persistent pain in the joints.
• Skin Reactions: Development of blisters or peeling of the skin (bullous pemphigoid).
• Low Blood Sugar (Hypoglycemia): This is more likely if Janumet is taken with other diabetes medications like insulin or sulfonylureas. Symptoms include shakiness, sweating, fast heartbeat, and dizziness.

Lactic Acidosis

Janumet contains metformin, which carries a boxed warning for a rare but serious condition called lactic acidosis. This occurs when metformin builds up in the blood, causing a medical emergency that requires immediate hospitalization. The risk is higher for individuals with kidney impairment, liver disease, or congestive heart failure, and for those who consume excessive amounts of alcohol or undergo certain radiological procedures with contrast dye.

Pancreatitis

Acute pancreatitis, including fatal and non-fatal cases, has been reported in patients taking sitagliptin. Healthcare providers monitor for signs such as severe abdominal pain that may radiate to the back. If pancreatitis is suspected, the medication is typically discontinued and not restarted.

Heart Failure

There is an observed association between DPP-4 inhibitors, such as sitagliptin, and an increased risk of heart failure. This risk is particularly relevant for patients who already have heart or kidney disease. Symptoms to watch for include unusual tiredness, shortness of breath, or swelling in the legs and feet.

Kidney Function

Because metformin is primarily excreted by the kidneys, Janumet is contraindicated in patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m2). Kidney function is usually evaluated before starting the drug and monitored at least annually during treatment.

Additional Precautions

• Vitamin B12 Levels: Long-term use of metformin may decrease vitamin B12 absorption, potentially leading to deficiency. Periodic blood tests may be used to monitor levels.
• Hypoglycemia: While Janumet alone does not typically cause low blood sugar, the risk increases significantly when it is used in combination with insulin or insulin secretagogues like sulfonylureas.
• Severe Joint Pain: Some patients taking DPP-4 inhibitors have reported severe and disabling joint pain. Symptoms may appear shortly after starting the drug or after years of use.
• Hypersensitivity Reactions: Serious allergic reactions, including anaphylaxis, angioedema, and severe skin conditions like Stevens-Johnson syndrome, have been reported.

Pregnancy

Maintaining stable blood sugar levels is important during pregnancy to reduce risks to both the parent and the baby. There is currently limited research on the safety of using Janumet during pregnancy. In many cases, healthcare providers prefer using insulin to manage diabetes in pregnant patients because its effects are better understood in this population.

Metformin, one of the active ingredients in Janumet, may stimulate ovulation in some premenopausal women who do not ovulate regularly. This can increase the likelihood of becoming pregnant. If pregnancy is not desired, it is important to discuss contraception options with a healthcare professional.

Breastfeeding

The decision to breastfeed while taking Janumet involves considering the potential risks to the infant and the benefits of the medication for the parent. The components of Janumet affect breastfeeding differently:

• Metformin: This drug is known to pass into breast milk in small quantities.
• Sitagliptin: It is not yet known if sitagliptin passes into human breast milk, though it has been found in the milk of animals during laboratory studies.

Because the effects on a nursing infant are not fully established, a healthcare provider can help determine the most appropriate treatment plan during this time.

Oral Tablet Forms

Janumet is available as a combination medication in oral tablet form. It is supplied in two different formulations:

• Film-Coated Tablets: These are immediate-release tablets intended for oral use.
• Extended-Release Tablets: These tablets are formulated to release the active ingredients into the system gradually. This version is typically identified as Janumet XR.

Both formulations are designed to be swallowed whole. The extended-release tablets should not be split, crushed, or chewed, as this can affect how the medication is released into the body.

FDA Approval and Indications

Janumet is approved by the U.S. Food and Drug Administration (FDA) as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is a combination of two previously approved medications: sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and metformin hydrochloride, a biguanide.

Boxed Warning

The FDA requires a boxed warning for Janumet due to the risk of lactic acidosis associated with the metformin component. Lactic acidosis is a rare but serious metabolic complication that can occur if metformin builds up in the blood. It is a medical emergency that requires immediate treatment in a hospital. Risk factors include:

• Renal impairment
• Older age (65 years or older)
• Radiological studies using contrast dye
• Surgery or other procedures
• Hypoxic states (such as acute heart failure)
• Excessive alcohol intake
• Hepatic impairment

Regulatory Updates on Kidney Function

The FDA revised the labeling for all metformin-containing products to change the way kidney function is assessed. Previously, serum creatinine levels were used; however, the FDA now requires the use of the estimated glomerular filtration rate (eGFR). Janumet is contraindicated in patients with severe renal impairment, defined as an eGFR below 30 mL/min/1.73 m2. The FDA also recommends against starting Janumet in patients with an eGFR between 30 and 45 mL/min/1.73 m2.

Safety Communications

The FDA has monitored reports of acute pancreatitis in patients using sitagliptin. While a definitive causal link is not established, the FDA-approved labeling includes warnings and precautions regarding the risk of pancreatitis. Healthcare providers are advised to monitor patients for signs of this condition and to discontinue the medication if pancreatitis is suspected.

Prescription Status

Janumet is a brand-name prescription medication. The total cost to the patient is generally determined by the terms of their health insurance policy and the pharmacy's pricing structure.

Insurance Coverage

Many insurance plans and Medicare programs include Janumet on their formularies. However, because it is a combination brand-name drug, it may be placed in a higher cost-sharing tier than generic medications. Patients are encouraged to check their plan's specific coverage details for copay or coinsurance amounts.

Cost Variations

The price of Janumet can vary depending on the dosage strength and the quantity of tablets dispensed. Comparing prices at different pharmacies or utilizing mail-order options provided by insurance companies may help in managing the overall expense of the medication.