Having insulin-dependent diabetes means a lifelong dependence on daily injections of insulin. In addition to people with type 1 diabetes, those with type 2 diabetes that is unresponsive to oral drugs must also take insulin.1
A typical patient with type 1 diabetes may need more than 60,000 injections across their lifetime, requiring two or more injections every day.2
"Ever since the introduction of insulin for the treatment of diabetes, methods of administering it other than by injection have been investigated." That is a quote from a paper published in The Lancet in 1940, and investigations continue to this day.3
The main obstacle to finding a way of delivering insulin in pill form is the digestive system itself - either the gut breaks the insulin down or the insulin moves through intact because it is unable to pass through the gastrointestinal membrane.2
Different preparations of insulin
In the US, all insulin that is sold has been manufactured in a laboratory. Although animal insulins used to be available, preparations from pigs and cattle have now been withdrawn from the market. Information and warnings about importing these animal preparations from abroad have been published by the US Food and Drug Administration.4-6
Analogs of human insulin are manufactured forms with some structural changes built in, differing in their amino acid sequence to alter their pharmacological characteristics.6
Insulin can be manufactured to produce different actions. The rapid-acting insulins are insulin glulisine, insulin lispro and insulin aspart. Short-acting insulins are insulin regular, while intermediate-acting insulins are neutral protamine Hagedorn (NPH) insulin, also known as isophane insulin. Finally, the long-acting insulins are insulin detemir and insulin glargine.4
Different preparations of insulin provide a range of options in terms of how quickly they take effect, their peak time of action and their overall duration of effect:4,5
- Rapid-acting insulin analogs have an onset of action at between 5-15 minutes, a peak action at 30-90 minutes and an overall duration of effect of 3-5 hours
- Short-acting, regular insulin has an onset of action at between 30-60 minutes, a peak action at 2-3 hours and an overall duration of effect of 5-8 hours. The optimum time for injecting is 30 minutes before eating
- Intermediate-acting insulins have an onset of action at between 2-4 hours, a peak action at 4-12 hours and an overall duration of effect of 10-18 hours
- Long-acting insulins have an onset of action at between 2-10 hours, a peak action at 6-16 hours (except insulin glargine, which has no peak) and an overall duration of effect of 16-24 hours. These insulins maintain glucose levels fairly uniformly over a 24-hour period.
Insulins may also be mixed at 30:70, 25:75 and 50:50 combinations to produce two peak times of action.5
Practical advice for injecting insulin
With practice and good technique, injecting insulin can become more comfortable. The needle is very small, and injection is not into a muscle or vein but under the skin. The three areas of skin most commonly used are the stomach, the buttocks and the thighs.7-9
The choice of site depends on a number of factors but can be rotated to help avoid the formation of lumps. Different sites result in different rates of absorption. Insulin is absorbed quickest through the abdomen, followed by the arm, and then the thigh and finally the buttocks.4,9 If physical exertion takes place after injection, this also increases absorption by increasing blood flow. Massage of the injection site also has an effect.8
Injections to the same area should be varied by keeping injections a couple of finger widths apart. Other practical tips include:8
- Avoiding the belly button, the inner thigh, the lower buttock, scars and broken blood vessels or varicose veins
- If using the thigh, keep injections at least 4 inches below the top of the leg and above the knee
- If using the arm, inject into the fatty area at the back, between the shoulder and elbow
- If using the buttock, use the hip area.
This video presented by a specialist diabetes nurse gives a step-by-step explanation of how to give insulin injections. The US National Library of Medicine have also produced a text guide to giving an insulin injection.
Insulin side effects
Very rarely, a serious and life-threatening allergic reaction can be experienced after insulin injection. This anaphylaxis is a medical emergency requiring immediate medical care. Serious insulin side effects and anaphylactic reactions are signaled by:1,10
- Rash or itching over the whole body
- Swelling (edema) of the tongue, throat, arms, hands, feet, ankles or lower legs
- Difficulty breathing or shortness of breath
- Difficulty swallowing
- Blurred vision
- Fast heartbeat (tachycardia) or abnormal heartbeat rhythm
- Muscle cramps
- Significant weight gain in a short period of time.
Gradually increasing insulin doses under medical supervision is used as a treatment to desensitize an individual with a severe insulin allergy.5,11
Side effects of insulin that are more common include:1,5,7
- Hypoglycemia - low blood sugar levels that can result from the timing of the insulin injection. Hypoglycemia might be avoided by shifting a pre-dinner dose of intermediate-acting insulin to bedtime, or reducing a bedtime dose
- Weight gain - this may happen initially when insulin therapy is started, due to correction of protein and energy metabolism. Later weight gain may be caused by fluid retention or excessive eating due to hypoglycemia
- Lipohypertrophy - raised lumps in the skin caused by repeated injections at the same site; this is can be prevented by the rotation of injection sites
- Other local effects - these are less common than lipohypertrophy and include infection, injection site abscess (both of which can be prevented with good injection practices), allergy and lipoatrophy (loss of fat tissue).
Human insulin inhalation powder (Afrezza) became available by prescription in the US in February 2015, the only inhaled insulin available at the time. It is available at around twice the cost of the injected rapid-acting insulins.12
Afrezza is a rapid-acting, dry-powder formulation of recombinant human insulin manufactured by Mannkind and Sanofi and may be used in the treatment of adults with type 1 or type 2 diabetes. In patients with type 1 diabetes, the drug must be used in combination with long-acting insulin.12
A single inhalation of Afrezza is taken at the beginning of meals.12
This is not the first inhaled insulin product to reach the market - a rapid-acting insulin, Exubera, was approved in 2006 but withdrawn just a year later by its manufacturer. That early device was a cumbersome size - about the size of a flashlight.12-14
The Afrezza insulin inhaler device.
Image credit: Sanofi/Mannkind.
Afrezza, however, is delivered via a smaller, palm-sized device that can be held comfortably between thumb and finger.
Long-term evidence on the safety of Afrezza is still to be gathered. To date, coughing has been identified as a common side effect, and there has been evidence of throat pain and irritation. As with other insulins, it can also lead to hypoglycemia.12
Patients with chronic lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are contraindicated from using Afrezza because it increases the risk of bronchospasm. The formulation should also be avoided by patients who smoke or have stopped smoking within the last 6 months.12
Inhaled insulin appears to be similarly effective to injected insulin at controlling blood glucose levels.6,8 One review says Afrezza should be reserved for otherwise healthy adults with diabetes who do not have lung disease and who are unwilling or unable to use injectable insulin.15