Side Effects of Starlix (nateglinide)

Starlix (nateglinide) is a meglitinide used to lower blood sugar (glucose) levels in type 2 diabetes. 

Type 2 diabetes usually occurs in adults and is associated with obesity and a strong family history of diabetes. Insulin is an important hormone that controls the blood level of glucose. 

Type 2 diabetics have an inability to control blood glucose levels. This is caused by reduced secretion of insulin from the pancreas after meals and resistance of the body's cells to the effect of insulin which is to stimulate the cells to remove glucose from the blood. This leads to high levels of blood glucose. 

Starlix stimulates cells in the pancreas to produce insulin in a manner similar to the class of drugs called sulfonylureas, for example, glyburide, which also are used in type 2 diabetes. 

However, Starlix appears to have a faster onset and a shorter duration of action than sulfonylureas. The benefit of this faster, shorter effect may be to prevent the rapid, transient rise in blood glucose that occurs in diabetics immediately following a meal.

Common side effects of Starlix include

• runny nose,
• cough,
• upper respiratory infections,
• back pain,
• flu-like symptoms,
• dizziness, and
• joint pain.

Serious side effects of Starlix include low blood glucose levels (hypoglycemia). Symptoms of hypoglycemia include

• hunger,
• nausea,
• tiredness,
• perspiration,
• headache,
• heart palpitations,
• numbness around the mouth,
• tingling in the fingers,
• tremors,
• muscle weakness,
• blurred vision,
• cold temperature,
• excessive yawning,
• irritability,
• confusion, and
• loss of consciousness.

Drug interactions of Starlix include nonsteroidal anti-inflammatory agents (NSAIDs), aspirin and aspirin-like compounds, monoamine oxidase inhibitors (MAOIs), and beta-blockers, because starting or stopping these drugs may increase the response to Starlix and may require the dose of Starlix to be lowered. 

Starting or stopping the following drugs may decrease the response to Starlix and may require the dose of Starlix to be increased:

• thiazide diuretics,
• steroids,
• thyroid hormone, and
• drugs used in emergencies to regulate the heartbeat or restore breathing when airways are blocked such as epinephrine and albuterol. 

No safety and efficacy studies have been conducted in pregnant women taking Starlix. Starlix should not be used during pregnancy. 

Since many drugs are excreted in breast milk, the manufacturer recommends Starlix not be administered to breastfeeding mothers.

The most common side effects of nateglinide therapy are:

• Runny nose,
• cough,
• upper respiratory infections,
• back pain,
• flu-like symptoms,
• dizziness, and
• joint pain are the most common side

Another important side effect of nateglinide therapy is hypoglycemia (low blood glucose levels with or without symptoms) can occur.

Some symptoms of hypoglycemia include:

• hunger,
• nausea,
• tiredness,
• perspiration,
• headache,
• heart palpitations,
• numbness around the mouth,
• tingling in the fingers,
• tremors,
• muscle weakness,
• blurred vision,
• cold temperature,
• excessive yawning,
• irritability,
• confusion, or
• loss of consciousness.

The following serious adverse reaction is also described elsewhere in the labeling:

Hypoglycemia

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.

In clinical trials, approximately 2,600 patients with type 2 diabetes mellitus were treated with Starlix. Of these, approximately 1,335 patients were treated for 6 months or longer and approximately 190 patients for one year or longer. Table 1 shows the most common adverse reactions associated with Starlix.

Table 1: Adverse Reactions other than Hypoglycemia (%) occurring Greater than or Equal to 2% in Starlix-Treated Patients from Pool of 12 to 64 week Placebo Controlled Trials

Hypoglycemia

Episodes of severe hypoglycemia (plasma glucose less than 36 mg/dL) were reported in two patients treated with Starlix. Non-severe hypoglycemia occurred in 2.4 % of Starlix treated patients and 0.4 % of placebo treated patients.

Weight Gain

Patients treated with Starlix had statistically significant mean increases in weight compared to placebo. In clinical trials, the mean weight increases with Starlix 60 mg (3 times daily) and Starlix 120 mg (3 times daily) compared to placebo were 1.0 kg and 1.6 kg respectively.

Laboratory Test

Increases in Uric Acid: There were increases in mean uric acid levels for patients treated with Starlix alone, Starlix in combination with metformin, metformin alone, and glyburide alone. The respective differences from placebo were 0.29 mg/dL, 0.45 mg/dL, 0.28 mg/dL, and 0.19 mg/dL.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Starlix. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Hypersensitivity reactions: Rash, itching, and urticaria
• Hepatobiliary Disorders: Jaundice, cholestatic hepatitis, and elevated liver enzymes

Table 2 includes a list of drugs with clinically important drug interactions when concomitantly administered or withdrawn with Starlix and instructions for managing or preventing them.

Table 2: Clinically Significant Drug Interactions with Starlix