Soliqua 100/33

Dosage of Insulin Glargine must be highly individualized based on the patient's metabolic needs, blood glucose monitoring results, and glycemic control goals.

• Type 1 Diabetes: Insulin Glargine is typically used as the basal component of a multidose injection regimen. For insulin-naive patients, the starting dose is usually approximately one-third to one-half of the total daily insulin requirement. The remainder of the daily dose should be administered as a short-acting, pre-meal insulin.
• Type 2 Diabetes: For patients not currently on insulin, a common starting dose is 0.2 units/kg or 10 units once daily. The dose is then titrated (adjusted) by 2 units every few days based on fasting plasma glucose levels until the target range is reached.
• Switching from other insulins: When switching from once-daily NPH to Insulin Glargine, the initial dose is usually the same. When switching from twice-daily NPH to once-daily Insulin Glargine, the initial dose is often reduced by 20% to avoid hypoglycemia.

Insulin Glargine is approved for use in pediatric patients with Type 1 diabetes.

• Age 2 to 17 years (U-100): Dosing is individualized similarly to adults. Clinical trials have shown that the safety and efficacy profiles in children are comparable to those in adults.
• Type 2 Diabetes in Children: While primarily studied in Type 1, healthcare providers may prescribe it for Type 2 in adolescents if oral agents are insufficient, following adult titration guidelines modified for weight.

Renal Impairment

Patients with kidney disease may require lower doses of Insulin Glargine. The kidneys play a role in insulin clearance; therefore, as renal function declines, insulin may stay in the system longer, increasing the risk of hypoglycemia. Frequent glucose monitoring is essential.

Hepatic Impairment

In patients with liver disease, insulin requirements may be reduced because the liver's capacity for gluconeogenesis and insulin metabolism is diminished. Dose adjustments should be made conservatively under medical supervision.

Elderly Patients

In the elderly (65 years and older), the initial dosing, increments, and maintenance dosages should be conservative. This population is at a higher risk for unrecognized hypoglycemia due to potential age-related declines in renal function and cognitive awareness.

1. 1Timing: Administer subcutaneously once daily at the same time every day. It does not matter what time of day is chosen, as long as it is consistent.
2. 2Injection Sites: Inject into the abdominal area, thigh, or deltoid (upper arm). Rotate injection sites within the same region to reduce the risk of lipodystrophy (thickening or pitting of the skin).
3. 3Preparation: The solution should be clear and colorless. Do not use if it is cloudy, colored, or contains particles.
4. 4Mixing: NEVER mix Insulin Glargine in the same syringe with any other insulin or solution. Mixing can change its absorption profile and lead to unpredictable blood sugar control.
5. 5Storage: Unopened vials and pens should be stored in the refrigerator (36°F–46°F). Once in use, vials and pens can typically be kept at room temperature for up to 28 days (refer to specific brand labeling, as some U-300 pens last up to 56 days).

If a dose is missed, take it as soon as you remember. However, if it is almost time for the next scheduled dose, skip the missed dose and return to the regular schedule. Never inject a double dose to make up for a missed one, as this significantly increases the risk of severe hypoglycemia.

An overdose of Insulin Glargine can lead to severe, life-threatening hypoglycemia.

• Signs: Extreme hunger, dizziness, confusion, tremors, sweating, palpitations, blurred vision, and seizure.
• Emergency Measures: If the patient is conscious, administer fast-acting carbohydrates (glucose tabs, juice, regular soda). If the patient is unconscious, glucagon should be administered by a trained caregiver, and emergency medical services (911) must be called immediately.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance.

• Hypoglycemia (Low Blood Sugar): This is the most frequent side effect of all insulin therapies, including Insulin Glargine. It occurs when blood glucose levels drop below the target range (typically <70 mg/dL). Patients may feel shaky, sweaty, anxious, or irritable. It often happens if a meal is skipped, during intense exercise, or if the dose is too high.
• Injection Site Reactions: Redness, swelling, itching, or pain at the site of injection. These are usually transient and resolve within a few days or weeks of continued use.
• Weight Gain: As insulin improves glycemic control and prevents glucose from being excreted in the urine, the body retains more calories, which can lead to weight gain. This is a common pharmacological effect of insulin therapy.

• Lipodystrophy: This refers to localized changes in fat tissue at the injection site. Lipohypertrophy (thickening of the fat tissue) can occur if the patient injects into the same spot too frequently. This can delay insulin absorption and lead to poor blood sugar control.
• Edema (Fluid Retention): Some patients may experience swelling in the ankles or feet, particularly when starting insulin therapy or after a significant improvement in blood sugar levels. This is often temporary.
• Pruritus (Itching): A generalized itchy sensation that is not necessarily localized to the injection site.

• Severe Allergic Reactions (Anaphylaxis): While rare, some individuals may develop a systemic allergy to Insulin Glargine or its excipients (like metacresol or zinc). Symptoms include generalized rash, shortness of breath, wheezing, rapid pulse, and low blood pressure.
• Hypokalemia (Low Potassium): Insulin causes a shift of potassium from the blood into the cells. In some cases, this can lead to dangerously low potassium levels, which can affect heart rhythm.
• Visual Changes: A sudden improvement in blood glucose control can cause a temporary shift in the fluid balance of the eye, leading to blurred vision. This usually resolves as the body adjusts.

> Warning: Stop taking Insulin Glargine and call your doctor immediately if you experience any of these.

1. 1Severe Hypoglycemia: Confusion, loss of consciousness, or seizures. This requires emergency intervention.
2. 2Systemic Allergic Reaction: Swelling of the face, tongue, or throat; difficulty swallowing; or severe hives. This may indicate anaphylaxis.
3. 3Hypokalemia Symptoms: Muscle cramps, profound weakness, or irregular heartbeats (arrhythmias).
4. 4Heart Failure Symptoms: Shortness of breath, sudden weight gain, or swelling of the legs and feet, especially if taking certain other diabetes medications like pioglitazone.

• Antibody Production: Some patients may develop antibodies to insulin over long periods. While usually not clinically significant, in rare cases, it may necessitate dose adjustments if the antibodies interfere with insulin action.
• Injection Site Scarring: Chronic injection into the same area without rotation can lead to permanent changes in the subcutaneous tissue, making future injections less effective.

No FDA black box warnings are currently issued for Insulin Glargine. However, it carries significant warnings regarding the risk of hypoglycemia and the danger of sharing insulin pens between patients, which can transmit bloodborne pathogens even if the needle is changed.

Report any unusual symptoms to your healthcare provider. Monitoring your body's response to insulin is a lifelong part of diabetes management.

Insulin Glargine is a potent medication that requires careful management. The most critical safety point is the prevention and recognition of hypoglycemia. Patients must be educated on the symptoms of low blood sugar and always carry a source of fast-acting carbohydrate. Furthermore, Insulin Glargine should never be used during episodes of hypoglycemia or in patients with a known hypersensitivity to the drug or its components.

No FDA black box warnings for Insulin Glargine.

• Never Share Pens or Syringes: Insulin Glargine pre-filled pens must never be shared between patients, even if the needle is changed. Sharing poses a critical risk for the transmission of bloodborne pathogens, including Hepatitis and HIV.
• Hypoglycemia Risk: The timing of hypoglycemia usually reflects the time-action profile of the insulin. With Glargine, the risk is distributed throughout the 24-hour period. Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose patients to hypoglycemia or hyperglycemia.
• Hypokalemia: All insulin products, including Glargine, cause a shift in potassium from the extracellular to the intracellular space. If left untreated, hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Use with caution in patients at risk for low potassium (e.g., those using potassium-lowering medications).
• Fluid Retention and Heart Failure: When used in combination with Thiazolidinediones (TZDs), such as pioglitazone or rosiglitazone, patients should be observed for signs of heart failure. If heart failure occurs, dosage reduction or discontinuation of the TZD must be considered.

Patients using Insulin Glargine require regular monitoring to ensure safety and efficacy:

• Self-Monitoring of Blood Glucose (SMBG): Patients should check their blood sugar levels multiple times daily, especially when starting the drug, changing doses, or during illness.
• HbA1c: This test should be performed every 3 to 6 months to assess long-term glycemic control.
• Potassium Levels: Healthcare providers may monitor serum potassium in patients at risk for hypokalemia.
• Renal and Hepatic Function: Periodic checks of kidney and liver function are recommended, as these organs affect insulin metabolism and clearance.

The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. This presents a risk in situations where these abilities are especially important, such as driving or operating heavy machinery. Patients should be advised to take precautions to avoid hypoglycemia while driving.

Alcohol can either increase or decrease the blood-glucose-lowering effect of insulin in an unpredictable manner. Consuming alcohol on an empty stomach significantly increases the risk of severe, delayed hypoglycemia. Patients should discuss alcohol consumption with their doctor and monitor blood sugar more frequently if they choose to drink.

Insulin Glargine should not be stopped abruptly in patients with Type 1 diabetes, as this will lead to rapid hyperglycemia and potentially life-threatening diabetic ketoacidosis (DKA). In Type 2 diabetes, discontinuation may lead to severe hyperglycemia. Any changes to insulin therapy must be done under the direct supervision of a healthcare provider.

> Important: Discuss all your medical conditions with your healthcare provider before starting Insulin Glargine.

There are no specific drugs that are absolutely contraindicated with Insulin Glargine in the sense of a 'never-use' chemical reaction, but it must NEVER be mixed in the same syringe with any other insulin or injectable medication. Mixing alters the pH-dependent absorption of Glargine, rendering its long-acting properties unpredictable and potentially causing dangerous fluctuations in blood sugar.

• Thiazolidinediones (TZDs): Drugs like pioglitazone can cause dose-related fluid retention when used with insulin. This increases the risk of congestive heart failure. Patients should be monitored for sudden weight gain, edema, and shortness of breath.
• Pramlintide: When starting this amylin analog, the dose of Insulin Glargine may need to be reduced by 50% to prevent severe hypoglycemia.

• Drugs that Increase Hypoglycemia Risk: The following may enhance the blood-glucose-lowering effect of insulin: oral antidiabetic products, ACE inhibitors (e.g., lisinopril), Angiotensin II receptor blockers, sulfonamide antibiotics, and fibrates. Close monitoring and dose reductions of Glargine may be necessary.
• Drugs that Decrease Glucose-Lowering Effect: Certain medications can raise blood sugar, requiring an increase in the Insulin Glargine dose. These include corticosteroids (e.g., prednisone), antipsychotics (e.g., olanzapine), estrogens, oral contraceptives, and thyroid hormones.
• Beta-Blockers: These medications (e.g., metoprolol) can mask the 'warning signs' of hypoglycemia, such as tremors and palpitations. However, sweating is usually not masked.

• Consistent Carbohydrate Intake: Insulin Glargine is a basal insulin, but its effectiveness is tied to the patient's overall diet. Large, inconsistent changes in carbohydrate intake can lead to glycemic instability.
• Alcohol: As mentioned, alcohol can potentiate the hypoglycemic effect of insulin and should be used with extreme caution.

• Chromium and Magnesium: These minerals may slightly increase insulin sensitivity, potentially increasing the risk of hypoglycemia.
• Fenugreek and Ginseng: Some studies suggest these herbs have glucose-lowering properties. Using them alongside Insulin Glargine requires careful monitoring.
• St. John's Wort: May affect blood glucose levels through various metabolic pathways, though the effect is often unpredictable.

Insulin Glargine does not typically interfere with standard laboratory tests. However, it will naturally affect blood glucose and HbA1c results, which are the intended targets of the therapy. It may also transiently lower serum potassium levels.

For each major interaction, the management strategy usually involves more frequent blood glucose monitoring and proactive dose adjustments.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking.

1. 1Hypersensitivity: Insulin Glargine is strictly contraindicated in patients who have had a severe allergic reaction (e.g., anaphylaxis) to Insulin Glargine or any of its inactive ingredients (such as zinc, m-cresol, or glycerol). A severe reaction can be life-threatening and requires immediate medical intervention.
2. 2Episodes of Hypoglycemia: Insulin Glargine must never be administered during an active episode of hypoglycemia. Doing so will further lower blood sugar levels, potentially leading to coma, seizures, or death.

• Hypokalemia: Patients with untreated low potassium levels should be stabilized before starting or increasing the dose of Insulin Glargine, as insulin can further lower potassium levels.
• Renal or Hepatic Impairment: While not an absolute contraindication, these conditions require extreme caution and frequent dose adjustments due to the altered metabolism of insulin.
• Visual Impairment: Patients with severe retinopathy or those who are blind may have difficulty accurately measuring doses or using injection pens, requiring the assistance of a caregiver.

Patients who have experienced allergic reactions to other insulin analogs (such as Insulin Detemir or Insulin Degludec) may be at an increased risk of cross-sensitivity with Insulin Glargine. While the molecular structures differ, the presence of similar preservatives or stabilizers in the formulations can trigger similar immune responses. A medically supervised 'test dose' or skin prick testing may be required in patients with a history of multiple insulin allergies.

> Important: Your healthcare provider will evaluate your complete medical history before prescribing Insulin Glargine.

Insulin Glargine is widely used in pregnancy. According to the FDA-approved labeling and various clinical registries, data from randomized controlled trials and observational studies have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Maintaining optimal glycemic control is critical during pregnancy, as poorly controlled diabetes increases the risk of macrosomia (large baby), neonatal hypoglycemia, and preeclampsia. Insulin Glargine is often preferred over some other analogs due to its long history of use and documented safety profile in pregnant women.

Insulin Glargine is excreted in human milk, but it is not expected to cause adverse effects in the nursing infant. Insulin is a large protein molecule that is mostly degraded in the infant's digestive tract if swallowed. Breastfeeding mothers may require adjustments in their insulin dose and caloric intake, as lactation significantly increases energy expenditure and can lower maternal blood sugar levels.

Insulin Glargine (U-100) is approved for use in children aged 2 years and older with Type 1 diabetes. Its use in children under 2 years of age or in children with Type 2 diabetes has not been extensively studied in clinical trials, although it is often used off-label in the latter group. Growth, pubertal development, and lifestyle changes in children require frequent dose adjustments. Healthcare providers must ensure that caregivers are thoroughly trained in pediatric-specific hypoglycemia management.

In clinical trials, a large number of patients over 65 have used Insulin Glargine. While no overall differences in safety or effectiveness were observed between these patients and younger patients, the elderly are more prone to hypoglycemia. This may be due to age-related declines in kidney function or a reduced 'autonomic' response to low blood sugar (meaning they don't feel the shakes or sweats as clearly). Dosing should be conservative.

The requirements for Insulin Glargine may be reduced in patients with renal impairment. As the Glomerular Filtration Rate (GFR) drops, the half-life of insulin increases. Patients on dialysis may also experience significant fluctuations in blood sugar and require close monitoring by a specialist.

Similar to renal impairment, liver disease can reduce the body's ability to clear insulin and produce glucose. Patients with high Child-Pugh scores (indicating severe liver dysfunction) require very careful titration and frequent blood glucose checks.

> Important: Special populations require individualized medical assessment.

Insulin Glargine is a human insulin analog produced by recombinant DNA technology using Escherichia coli. The primary activity of insulin, including insulin glargine, is the regulation of glucose metabolism. It binds to insulin receptors on muscle and fat cells, facilitating glucose uptake, and simultaneously inhibits glucose output from the liver. Glargine is unique because of two specific modifications to the human insulin molecule: the substitution of the amino acid glycine for asparagine at position A21 and the addition of two arginines to the C-terminus of the B-chain. These changes shift the isoelectric point from a pH of 5.4 to 6.7, making the molecule more soluble at an acidic pH and less soluble at the neutral pH of the subcutaneous tissue.

After subcutaneous injection, Insulin Glargine acts over a period of approximately 24 hours. Its pharmacodynamic profile is characterized by a 'peakless' curve, which provides a more stable and predictable glucose-lowering effect compared to NPH insulin. This stability reduces glycemic variability, which is a key factor in preventing long-term diabetic complications. The duration of action is dose-dependent but generally lasts 20 to 24 hours for U-100 and up to 36 hours for U-300.

| Parameter | Value |

|---|---|

| Bioavailability | Variable (Subcutaneous absorption is rate-limiting) |

| Protein Binding | <5% (Circulates as free insulin) |

| Half-life | ~12-24 hours (Effective half-life after SC injection) |

| Tmax | No pronounced peak (Steady state in 2-4 days) |

| Metabolism | Cleaved into active metabolites M1 and M2 |

| Excretion | Primarily Renal (as metabolites) |

• Molecular Formula: C267H404N72O78S6
• Molecular Weight: 6063 Daltons
• Solubility: Soluble in acidic media (pH 4); forms microprecipitates at pH 7.4.
• Structure: Consists of an A-chain and a B-chain linked by disulfide bonds, with specific amino acid substitutions at A21 and B30.

Insulin Glargine is classified as a Long-acting Insulin Analog. It is distinct from rapid-acting analogs (like Lispro) and intermediate-acting insulins (like NPH). It is often used in combination with other drug classes, such as GLP-1 receptor agonists, in fixed-dose combinations to provide both basal coverage and post-prandial (after-meal) glucose control.