Insulin Degludec

What Does Insulin Degludec Do?

Insulin degludec is an ultra-long-acting insulin analogue designed to manage high blood sugar levels (hyperglycaemia) in individuals with Type 1 and Type 2 diabetes. By facilitating glucose uptake into cells and inhibiting glucose production from the liver, insulin degludec helps alleviate the symptoms associated with uncontrolled diabetes, thereby improving overall metabolic control.

How Does Insulin Degludec Work? (the complicated stuff!)

Insulin degludec functions as an ultra-long-acting insulin by forming multi-hexamers upon subcutaneous injection, creating a depot for gradual absorption into the bloodstream. This process results in a prolonged action of more than 24 hours. Insulin degludec binds to insulin receptors, promoting glucose uptake into cells through the activation of glucose transporter 4 (GLUT4) and simultaneously inhibiting hepatic glucose production by downregulating gluconeogenesis and glycogenolysis. Additionally, it enhances protein synthesis and reduces lipolysis, thereby maintaining energy homeostasis.

Drug Type and Category of Insulin Degludec

Insulin degludec is classified as an ultra-long-acting insulin analogue. It falls under the category of medications used for the management of diabetes mellitus, specifically Type 1 and Type 2 diabetes. 

What dosage of Insulin Degludec should you be taking?

NICE Guidelines ¹

For Insulin-Naive Patients with Type 2 Diabetes:

• Starting Dose: The typical initial dose is 10 units administered once daily.

For Insulin-Naive Patients with Type 1 Diabetes:

• Starting Dose: Initiate with one-third to one-half of the total daily insulin requirement as insulin degludec, with the remainder provided by short-acting insulin divided among meals.

For Patients Switching from Another Basal Insulin:

• Dose Conversion: When transitioning from another basal insulin to insulin degludec, the dose can typically be converted unit-to-unit based on the previous basal insulin dose. However, individual adjustments may be necessary based on blood glucose monitoring and clinical judgment.

Administration Guidelines:

• Frequency: Administer insulin degludec once daily, preferably at the same time each day. On occasions when this is not feasible, the timing can be flexible, provided there is a minimum of 8 hours between doses.
• Available Strengths: Insulin degludec is available in two concentrations: 100 units/mL and 200 units/mL. The pen device displays the number of units to be injected, regardless of the insulin strength, eliminating the need for dose conversion when switching between concentrations.

What are the side-effects of Insulin Degludec?

Common Side Effects:

1. Hypoglycemia (Low Blood Sugar)
• Symptoms: Sweating, shakiness, confusion, rapid heartbeat, hunger, dizziness, or fainting.
• Hypoglycemia is the most common side effect of all insulin therapies. It is, after all, a drug that lowers blood sugar levels. 
2. Injection Site Reactions
• Symptoms: Redness, swelling, itching, or pain at the injection site.
• These reactions are usually mild and resolve on their own.
3. Weight Gain
• Related to improved glucose metabolism and the anabolic effects of insulin.

Less Common Side Effects:

1. Allergic Reactions
• Symptoms: Rash, itching, hives, or more severe symptoms such as difficulty breathing (rare).
• Can be localised or systemic.
2. Lipodystrophy
• Symptoms: Changes in the fat tissue under the skin at the injection site (lipoatrophy or lipohypertrophy).
• Prevented by rotating injection sites.
3. Peripheral Edema
• Symptoms: Swelling of the hands, feet, or ankles.
• Often due to fluid retention.

Serious Side Effects (Rare):

1. Severe Hypoglycemia
• Can cause seizures, unconsciousness, or even death if untreated.
• Requires immediate medical attention.
2. Severe Allergic Reactions (Anaphylaxis)
• Symptoms: Widespread rash, difficulty breathing, swelling of the face or throat.
• Requires emergency treatment.
3. Hypokalemia (Low Potassium Levels)
• Symptoms: Muscle weakness, cramping, irregular heartbeat.
• Rare but serious; requires monitoring in high-risk patients.

Precautions to Minimise Side Effects:

1. Blood Glucose Monitoring
• Regular monitoring helps avoid hypoglycemia or hyperglycemia.
2. Rotating Injection Sites
• Prevents lipodystrophy and injection site irritation.
3. Avoiding Overdosing
• Doses should be individualised and adjusted based on blood glucose levels.
4. Education on Hypoglycemia
• Patients should understand how to recognise and treat low blood sugar.

Interactions

Medications That Can Increase the Risk of Hypoglycemia:

1. Oral Antidiabetic Drugs
• Examples: Sulfonylureas (e.g., glimepiride), meglitinides.
• Combined use can enhance the glucose-lowering effect.
2. Beta-Blockers
• Mask hypoglycemia symptoms (e.g., rapid heartbeat) while increasing the risk of hypoglycemia.
3. Alcohol
• Excessive consumption can increase the risk of delayed or severe hypoglycemia.
4. Angiotensin-Converting Enzyme (ACE) Inhibitors
• Examples: Lisinopril, enalapril.
• May enhance insulin sensitivity, increasing the risk of hypoglycemia.

Medications That Can Increase Blood Glucose Levels:

1. Corticosteroids
• Examples: Prednisone, dexamethasone.
• May counteract the effects of insulin, leading to hyperglycemia.
2. Thiazide Diuretics
• Examples: Hydrochlorothiazide, chlorthalidone.
• Can reduce insulin effectiveness, raising blood glucose levels.
3. Sympathomimetic Drugs
• Examples: Epinephrine, salbutamol (used in asthma inhalers).
• May increase blood glucose levels.
4. Hormonal Therapies
• Examples: Oral contraceptives, thyroid hormones.
• Can elevate blood glucose levels, requiring insulin dose adjustments.

Medications That May Mask Hypoglycemia Symptoms:

1. Beta-Blockers
• Examples: Metoprolol, propranolol.
• Can blunt symptoms like tremor, palpitations, or sweating, making hypoglycemia harder to detect.
2. Clonidine
• May interfere with the body’s response to low blood sugar.
3. Reserpine
• Similar masking effects on hypoglycemia symptoms.

Other Considerations:

1. Concomitant Use with Other Insulins
• Combining long-acting insulin (like degludec) with other types of insulin may increase the risk of hypoglycemia or lead to unpredictable glucose control.
2. Concurrent Illness or Stress
• Acute illnesses, infections, or stress can alter insulin requirements and interact with medications used during treatment.
3. Potassium-Lowering Drugs
• Examples: Loop diuretics, certain antibiotics.
• Insulin can cause hypokalemia, and concurrent use of these drugs may exacerbate this risk.

Natural Alternatives to Insulin Degludec

1. Dietary Modifications

• Low-Carbohydrate Diets: Reducing carbohydrate intake can improve blood sugar control by minimising glucose spikes after meals².
• Mediterranean Diet: Emphasising whole grains, fruits, vegetables, nuts, and healthy fats has been associated with better glycemic control².
• Intermittent Fasting: Emerging evidence suggests that time-restricted eating may improve insulin sensitivity and reduce fasting blood glucose levels³.

2. Herbal Remedies

• Fenugreek (Trigonella foenum-graecum): Contains soluble fiber that may lower postprandial blood glucose levels by delaying carbohydrate digestion and absorption⁴.
• Cinnamon (Cinnamomum spp.): Studies suggest it may improve insulin sensitivity and fasting blood glucose levels in type 2 diabetes patients⁵.
• Berberine: A compound found in plants like Berberis species, it has been shown to reduce blood glucose levels and enhance insulin sensitivity⁶.

3. Physical Activity

• Aerobic Exercise: Regular aerobic activity, such as walking or cycling, improves insulin sensitivity and reduces blood sugar levels⁷. You’ve probably heard of the saying “exercise burns sugar”. 
• Resistance Training: Building muscle through strength exercises enhances glucose uptake by muscle cells, aiding glycemic control⁸.
• Yoga: Yoga practices may help lower stress levels, improve glycemic control, and enhance overall well-being⁹.

4. Supplements

• Chromium: Chromium picolinate has been associated with improved insulin function and better glucose metabolism¹⁰.
• Magnesium: Magnesium deficiency is linked to insulin resistance, and supplementation may improve insulin sensitivity¹¹.
• Vitamin D: Maintaining adequate vitamin D levels supports glucose metabolism and reduces the risk of type 2 diabetes¹².

5. Stress Management

• Mindfulness and Meditation: Chronic stress can elevate blood glucose levels; mindfulness practices help manage stress and improve glycemic control¹³.
• Acupuncture: Some studies suggest that acupuncture may reduce blood glucose levels and enhance insulin sensitivity¹⁴. However, this probably cannot be relied on as solid evidence, even though acupuncture has other benefits. 

Interesting facts about Insulin Degludec

Insulin degludec has an action duration of over 42 hours, making it one of the longest-acting insulins available. This allows for more flexible dosing schedules compared to traditional basal insulins.

Unlike many other insulins that require strict timing, insulin degludec can be administered at different times of the day, provided there is a minimum of 8 hours between doses.

Its ultra-long and steady action profile minimises daily blood sugar fluctuations, making it easier to maintain consistent glucose control.

Due to its high-concentration formulation, insulin degludec reduces packaging and waste, contributing to a smaller environmental footprint.

Disclaimer

This article is generated for informational purposes only. It was created in March 2025. Medications and medical guidance can change over time. Therefore, it is essential to consult with your general practitioner or healthcare provider before making any decisions regarding medications or treatment plans. Your GP can provide personalised advice based on your specific health needs and conditions.

References

1. https://www.nice.org.uk/advice/esnm25/chapter/product-overview
2. Mansell, K., et al. (2021). "Dietary Patterns for Diabetes Management: A Review of Evidence." Journal of Nutrition Research.
3. Mattson, M. P., et al. (2019). "Intermittent Fasting and Human Metabolic Health." Annual Review of Nutrition.
4. Gupta, A., et al. (2017). "Fenugreek and its Effects on Blood Glucose Levels in Diabetes." Herbal Medicine Review.
5. Anderson, R. A. (2008). "Cinnamon Improves Glucose and Lipids of People with Type 2 Diabetes." Diabetes Care.
6. Yin, J., et al. (2008). "Berberine: A Potential Therapeutic Agent for Type 2 Diabetes." Diabetes Care.
7. Colberg, S. R., et al. (2010). "Exercise and Type 2 Diabetes." Diabetes Care.
8. Holten, M., et al. (2004). "Strength Training Increases Insulin Action in Skeletal Muscle." Journal of Clinical Endocrinology & Metabolism.
9. Innes, K. E., et al. (2007). "Yoga for Adults with Type 2 Diabetes: A Systematic Review." Diabetes Spectrum.
10. Anderson, R. A., et al. (1997). "Chromium Supplementation and Glucose Metabolism." Journal of Clinical Nutrition.
11. Song, Y., et al. (2006). "Magnesium Intake and Incidence of Type 2 Diabetes." Diabetes Care.
12. Pittas, A. G., et al. (2007). "Vitamin D and Diabetes Risk." Journal of Clinical Endocrinology & Metabolism.
13. Carlson, L. E., et al. (2003). "Mindfulness-Based Stress Reduction and Diabetes." Psychosomatic Medicine.
14. Choi, T. Y., et al. (2017). "Acupuncture for Glycemic Control in Type 2 Diabetes." Journal of Alternative and Complementary Medicine.