Diabetes Drugs: Insulin

Editor’s Note: This is the first post in our miniseries about diabetes drugs. Tune in on August 14 for the next installment.


insulinInsulin was the first medicine developed for the treatment of diabetes, and it remains the most effective therapy for treating hyperglycemia (high blood glucose).

The name insulin comes from the Latin insula which means island; it is so named because the beta cells, which produce insulin, are in a part of the pancreas called the islets of Langerhans. Insulin is a protein consisting of 51 amino acids. It is normally released into the blood in response to changes in blood glucose levels, but several hormones, nutrients, and drugs can also stimulate its release.

Insulin therapy is required for all people with Type 1 diabetes and for many people with Type 2 diabetes. While people with Type 1 diabetes lack insulin secretion due to the autoimmune destruction of the pancreatic beta cells (a process in which the immune system recognizes the beta cells as foreign to the body, and so attacks them), people with Type 2 diabetes have a mixture of insensitivity to insulin (called insulin resistance) and a decrease in insulin secretion (which may be due either to poorly functioning beta cells or to a decrease in the amount of beta cells).

Insulin reduces blood glucose levels by interacting with a protein on the surface of cells called the insulin receptor. There are two known types of insulin receptor that both serve the same purpose. The interaction between insulin and the insulin receptor triggers a complex series of reactions that are to date not fully understood, but that serve to increase the creation of protein, glycogen (a storage form of glucose), and most importantly, glucose transport proteins (proteins that bring glucose from the blood into the cell), thereby reducing blood glucose levels. Because of these actions, insulin is classified as an anabolic, or energy-storing, hormone.

Insulin receptors are most prominent on liver, muscle, and fat cells. These organs, which are the main target tissues for insulin, are termed insulin-sensitive organs, meaning that they require insulin to use glucose from the blood; organs that have fewer insulin receptors, such as the brain, do not depend on insulin for glucose transport into the cells.

Insulin that is secreted by the pancreas has a circulating half-life of approximately 6 minutes, which is to say that every 6 minutes, the amount of insulin in the blood declines by 50%. In fact, after it is released from the pancreas, insulin is no longer detectable in the bloodstream within 30 minutes. Insulin is removed from the body by enzymes in the kidney and the liver, as well as by its interaction with insulin receptors.

Insulin as a Treatment
Since insulin is a protein, it can only be given by injection into subcutaneous tissues (tissues just under the skin) or intravenous administration directly into the bloodstream. (Insulin is broken down by stomach acids if swallowed.) However, alternate forms of insulin are currently being developed that can be taken by mouth, inhaled, or sprayed into the nose or the mouth. (Inhaled insulin was available a few years ago, but the company that made it removed it from the market due to poor sales.)

When insulin first became available to people with diabetes, it was directly obtained from the pancreases of animals, and was therefore called pork or beef insulin, depending on the source. Insulin is now made in the laboratory in a variety of forms, generally classified as human or human analogs. These insulins have various ranges of times over which they are effective at lowering blood glucose, and are accordingly classified as rapid-acting, short-acting, intermediate-acting, and long-acting. The onset of action, peak action, and duration of action of various types of insulin are as follows:

    Human insulin:
    Onset of action: 30–60 minutes
    Peak effect: 2–4 hours
    Duration of action: 6–8 hours

    Onset of action: 2–4 hours
    Peak effect: 4–6 hours
    Duration of action: 12–16 hours

    Lispro (brand name Humalog):
    Onset of action: 5–15 minutes
    Peak effect: 60 minutes
    Duration of action: 4–5 hours

    Aspart (NovoLog):
    Onset of action: 5–15 minutes
    Peak effect: 60 minutes
    Duration of action: 4–5 hours

    Glulisine (Apidra):
    Onset of action: 5–15 minutes
    Peak effect: 60 minutes
    Duration of action: 4–5 hours

    Glargine (Lantus):
    Onset of action: 2 hours
    Peak effect: peakless
    Duration of action: approximately 24 hours

    Detemir (Levemir):
    Onset of action: 2 hours
    Peak effect: peakless
    Duration of action: approximately 14–16 hours

Human insulin is made by genetic engineering and is exactly the same protein as that produced by the human pancreas. Insulin analogs, on the other hand, have slight differences in the amino acid sequence from human insulin. They retain the ability to interact with the insulin receptor but have altered absorption rates, either being faster or much slower than human insulin.

The goal of insulin therapy has always been to reflect the typical blood glucose patterns seen in a person without diabetes: In this case, the pancreas not only puts out insulin in response to a meal or snack, but it also secretes insulin at a constant low level throughout the day. This constant stream of insulin is referred to as basal insulin, while the insulin that covers a rise in blood glucose from a meal or snack is known as a bolus.

Approaches to Insulin Therapy
Insulin therapy is necessary for people with Type 1 diabetes (as well as for some with Type 2 diabetes); often the best way to administer the insulin is with an insulin pump, which can give both basal insulin and bolus insulin doses. Another approach to insulin administration is known as “multiple daily insulin injection regimens,” in which long-acting insulin is given by injection once or twice a day, and as many injections of rapid-acting insulin as needed are given to cover meals and snacks.

The 2009 Consensus Statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) indicates that after using a regimen of healthful eating and physical activity along with the oral medicine metformin, the next treatment option for people with Type 2 diabetes is a regimen of basal insulin. This would aim to control HbA1c (an indicator of blood glucose control over the previous 2–3 months) and fasting blood glucose levels, and rapid-acting insulins could be added as necessary to provide coverage for meals.

Treatment with insulin can have some significant side effects, including a weight gain of between 4–8 pounds and hypoglycemia (low blood glucose). Clinical trials that aimed to get participants to an HbA1c of roughly 7% have indicated that approximately 1–3 out of 100 people using insulin will have one episode of low blood glucose requiring assistance per year. However, this also means that 97 out of 100 people will not have an episode of severe hypoglycemia in that same one-year period. Moreover, insulin therapy is very effective at reducing blood glucose and HbA1c levels, as well as at raising HDL (“good”) cholesterol and lowering triglycerides (a type of blood fat).

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  • CalgaryDiabetic

    Using insulin to treat insulin resistance is like the old joke that the operation was a success but the patient died.

    Weight gain is a serious problem that will increase the insulin resistance on the otherhand letting the BG go to the moon will increase the insulin resistance and the triglicerides and the bad cholesterol. It seems as a die if you do and die if you don’t.

    A large amount of exercise does seem to help insulin resistance.

    Are there any drugs that help? In my case I get extremely tired if longer than 3 weks on metformin otherwise it is fine no gastro problems. Avandia had not effect either on the average BG nor on the standard deviation. Mind you this was before I went on insulin. Endo assures me that I am a type 2 because the fat is predominantly abdominal. Any further thoughts?

    Is changing insulins every so often a good idea. I tried Levemir instead of Lantus and unit for unit can’t really say there was much difference. I was wondering if switching from novo to apidra might do something?

  • Mark T. Marino

    The diagnosis of adult-onset diabetes is not always straightforward. There is a condition called latent autoimmune diabetes of adults, or LADA, that may occur in up to 10% of people with diabetes who initially do not require insulin. You should discuss this with your health-care provider; if appropriate, he could check for this condition with various blood tests. A diagnosis of LADA might have implications for your therapy, since there is some evidence that people with this condition have more of an insulin deficiency than people with Type 2 diabetes. However, no large studies have been done to help determine the best therapy for LADA.

    With that said, the goal is to optimize the current insulin therapy you are on. As mentioned in “Diabetes Drugs: Insulin,” the best method of insulin administration is to combine long-acting and rapid-acting insulin to provide good blood glucose control throughout the day without causing hypoglycemia (low blood glucose). I would suggest that you work closely with your health-care provider to optimize your blood glucose control. This may mean more frequent blood glucose measurements throughout the day to determine how to change your daily doses. Another option you may want to explore with your health-care provider is an insulin pump. And as always, a diet and exercise plan that is designed in partnership with your health-care provider is recommended.

  • Bill Young

    Great article on insulin, Mark. My question is in your experience, does insulin therapy protect the diabetic person from the complications of the disease, such as amputations, kidney failure or heart attack?

  • ShirleyKaye

    I just read the comments made on Aug 7 posted by Calgary Diabetic and my complaints are very similar. I am on Lantus and Apidra. Within two weeks on this medication I gained 9 pounds mostly in the waist area. I exercise regularly but the weight problem remains. Doesn’t this defeat the problem? How can I help myself?

  • Mary Jane

    Just read Aug 11 posted by ShirleyKaye I also have a weight problem and fluid retention problem but I am on Humulin 70/30 and Humulin R every day and can’t seem to lose weight. I can’t exercise due to heart and Lung problems. Can you suggest something that I can do besids lo-fat, low -sodium which I follow. Thanks

  • Howard Kinney

    I am losing my insurance in a couple of months and can not afford analog insulin ($115 btl). Why can’t I make adjustments and use regular insulin($20 btl) in my pump? Since I use a bottle every week it will either be changing or quit the pump and go back to shots.

  • Allen Robinson

    It seems to me that over the last 10 years all treatments have led to weight gain. Now I am on both long and short term insulin. Why it that no one will treat the weight problem. My treatments all seem lead the same place, my death, because doctors and insurance companies are not that interested in helping me feel better. I do 30 to 60 minutes of cardio exercise 5 days a week and lift weights 3 days plus swim. I still feel so bad that after working out all I can do is go back to bed. I do not see how I will ever work again with out some new treatment.

  • Paula Kilburn

    I’m on an insulin pump now for 3 yrs. Been Type I diabetic for 42 yrs. I’m also noticing a larger mid-section but the weight does not fluctuate much. The isn’t enough time in a day nor energy in my body to exercise like my doctor suggests. I go to Curves 3x a week and am active with housework and yard work all the time.Isn’t there a happy medium between what I eat and the amount of exercising needed? I’m not getting any younger!

  • Mark T. Marino

    The goal of any therapy for diabetes is to keep blood glucose levels within the target range. In multiple large clinical trials such as the Diabetes Complications and Control Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) Study, which looked at people with Type 1 diabetes, and the United Kingdom Prospective Diabetes Study (UKPDS), which looked at people with Type 2 diabetes, complications were significantly reduced by improved blood glucose control. The beneficial effects in the UKPDS study occurred regardless of the drug used to obtain good control (including insulin).

    As noted in “Diabetes Drugs: Insulin,” insulin is an energy-storing hormone that can be associated with weight gain. There are many potential reasons for insulin causing weight gain, but one possible reason is that the insulin produces a lower blood glucose level than your body is used to, which leads to “defensive” eating to combat the perceived hypoglycemia. You should keep track of your diet and your blood glucose levels during the day in a diary that you can review with your health-care provider.

    There are several drugs for Type 2 diabetes, including metformin (brand name Glucophage and others) and exenatide (Byetta), that do not produce weight gain or that produce weight loss. However, none of them are as effective at improving HbA1c (an indicator of blood glucose control over the previous 2–3 months) as insulin. You should discuss with your doctor what other options might be of use in your specific circumstances.

  • Elaine Finney


  • Bernard Farrell

    Thanks for this information about insulin.

    I’d love to understand how exercise makes insulin more effective. I’ve got type 1 and I know that when I exercise I need less insulin, sometimes even no insulin, even if I consume carbs while doing this.

    I’ve never understood how this mechanism works and would love some insight.

    Diabetes Technology Blog

  • Mark T. Marino

    Insulin allergy does occur, but it is relatively rare. Medically speaking, an allergy to insulin usually involves the development of a very specific class of antibodies called IgE antibodies. (This is the same class of antibodies that causes allergies to other drugs, such as penicillin.) IgE antibodies are not to be confused with insulin antibodies, which do occur in many people who receive insulin. These insulin antibodies are of the IgG class and do not cause an “allergic” reaction. To read about a person with a true insulin allergy, click here.

    Insulin requirements vis-à-vis exercise is a very large topic. A person’s blood glucose response to exercise depends on how well the person’s blood glucose is in control and the type and intensity of the exercise, as well as the person’s level of physical fitness. In general, glucose uptake in muscle depends on glucose transporters (proteins that serve to ferry glucose into the cell) in the muscle cell membrane, and these are known to increase during exercise and to stay elevated for several hours after exercise. Many other aspects of how these transporters and other signals are stimulated by exercise are not fully known. For more details, see the book Nutritional Applications in Exercise and Sport, by Ira Wolinsky and Judy A. Driskell, as well as the article “Exercise-induced increase in muscle insulin sensitivity.”

    Regular insulin can be used in a pump, but I would check both with your health-care provider and the insulin pump manufacturer before taking this route: Since Regular insulin is not absorbed into the bloodstream as quickly as a rapid-acting insulin analog, the insulin schedule your are currently on might need to be modified, especially if it is a bolus and basal pump.

  • Pauline Fecht

    My body swells with metaformin, actos, and glimepriride. My legs swell so bad and hurt I can’t stand the pain.
    What other oral pill can I take? I take diovan and lasix also and 20 units lantus insulin.

  • Bea Atalig

    Was visiting relatives for 1 1/2 months on an island where fish and rice were main food. Was on Metformin and glyberide at that time. Was able to lose 17 pounds, but had so much swelling. After return home was taken off glyberide and put on Byetta(pen) and have lost 30 additional pounds with no swelling. Have continued the Metformin. My morning readings before change were in the 256-236 range. Now it can be 88-130 range depending what was eaten the evening before. I’m not always perfect in what I eat, but I have honestly tried to be much more aware of the carb intake for me and this seems to have helped me alot. Losing has helped me be more active each day. I have a long way to go and some days are good and some not so good, but I’m feeling better than I have in a long time!

  • Becky

    In most articles on diabetes I have read, LADA is often mentioned, but not MODY. I produce basal insulin, though not in great enough quantities, and apparently no bolus, resulting in 4 shots a day. Because I am diagnosed type 2, my insurance won’t cover a pump. One doctor I saw speculated I had MODY, but there is very little info, on it and no way to test except expensive genetic testing. Is MODY type 2 and do you ever have any info. about it? I have not tested positive for LADA.

  • Mark T. Marino

    MODY, otherwise known as “maturity onset diabetes of the young,” may represent approximately 5% of all cases of diabetes. While it is commonly diagnosed in childhood or adolescence, it can go undiagnosed until adulthood. MODY often runs in families. This is because it is caused by very specific genetic abnormalities, which are classified as autosomal dominant. Normally, you have two copies of each gene in your body, one from your mother and one from your father. In some diseases, both copies need to be abnormal to have the disease, but in autosomal dominant disorders, only one copy needs to be abnormal. This is usually passed down from a parent who also has a copy of the abnormal gene. This means there is a 50% chance a child of a person with this also getting the disease. While many people can be treated with diet, exercise, and oral therapy, some people may require insulin. For more details, along with other genetic causes for diabetes, see http://www.diabetes.niddk.nih.gov/dm/pubs/mody/#3 or http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=diabetes, Chapter 4.

  • carson

    I noticed you site primarily (exclusively?)focuses on pharmaceutical drugs. I currently manage a health food store and I would like to share with your readers the possiblities of controlling and stabilising blood sugar with super foods and nutritional supplements. Alot of improvements are based on simple ‘common sense’ changes in diet and lifestyle along with cornerstone products that may include a special ‘diabetic friendly multi vitamin’ with good levels of chromium and vanadium. Of course we always advise customers to proceed under the supervision of their doctor when introducing anything new in their treatment protocol or daily habits. Foods like chia seed that are naturally high in soluble fibre and omega 3 fatty acids and low in carbohydrate are perfect additions to the diet of anyone concerned about blood sugar, hight cholesterol, blood pressure or just maintaing good general health. I would encourage your readers to educate themselves around these choices and work with their health care practitioners to improve their nutritional status and quality of life. Thanks for the opportunity to share my thoughts. Wish everyone the best of health. Sincerely, Carson

  • Howard McCain

    At the age of 35 I discovered that I had a blood sugar on the high side of normal, it was 120. I avoided eating food with sugar and got regular exercise. At age 50 I started taking pills for blood sugar control and I stated jogging. At age 60, during a stressful personal experience, I started taking insulin. I took 30/70 insulin along with medformin. At age 66 I adopted the insulin sliding scale, Novalog {quick acting} and Novalin {long acting} insulin plus I continue to take medformin. Generally my glocohemiglobin test is about 6.0. My doctor compliments me on being able to keep it in that range. I am now 74, I have for years weighted 180, stand 5′ 11.5″. I have no symptoms. Exercise is the key for me, I now walk 3 miles a day, weather permitting. I am also careful what and how much I eat, but I eat a variety of delicious meals, I avoid sugar, off course. So far, so good for me. My one real problem is that I have fine tuned my insulin in take so fine, that I must be careful anytime I leave home, not to get too low a blood sugar level, I feel it when I do, and I always carry candy with me that brings it up quick.

  • ragarm

    This is in response to those asking how to defy the weight-gain prone tendencies that can develop eith insulin therapy.

    I’m a 49 year old, quite brittle Type 1 diabetic for about 25 years and I’m going to lay it out for you, my peeps: barring some unusual medical reasons, there is no way to lose weight while continuing to control your blood sugar (this is assuming your blood sugar *is* controlled : ) other than to lower the amount of insulin you take and there is no way to safely lower the amount of insulin you take other than to lower your caloric/carb intake at the same time (and TEST ’til you get it right!)

    How you do this may be more or less complicated depending on how well you metabolize food, what kind of diet you consume (more meat? more carbs? vegan?) and how much activity your daily routine includes, perhaps among other things.

    It’s not a trick; it’s not a lie; it’s just hard.

    Whether you are diabetic or not, most people eat more than they *need*; non-diabetics can often get away with this more easily — but not always!

    Insulin will effect the weight a person puts on —
    which is why, without injecting insulin, Type 1 diabetics will waste away to nothing before dying.

    That is to say — yes, insulin will promote weight gain but it is actually the calories/carbs consumed which comprise the weight gain.

    There is still so much not understood about diabetes — so take heart! Who knows what they’ll figure out next?

  • Keith

    I am posting to Howard Kinney’s req. you can use regular insulin in the pump but you will have to watch and balance everything bolusing probably 30 min to 60 min b4 meals, due to slower effect, talk with your endo on this though it isn’t for everyone.
    You also could try going on medicare or medicaid, depending on income you might qualify… going back to daily injections won’t give you the control the pump does, but costs are what seems to be your issue:( , check with your pump manufacturer also they might have some ideas, because they don’t want to lose your business as well

  • Cindy

    I have gained weight yet I am dieting & exercising my doctor does not believe me that insulin can cause weight gain. I wish there was something I could show him that would prove him worng!!!

  • Mark Marino

    I am attaching a link to a Web site with a review article discussing therapies for the treatment of diabetes. It clearly states that insulin is associated with weight gain. I hope it helps.


  • Confused and Frustrated

    I have always had insulin resistance, PCOS – Metabolic Syndrome; also had gestatinal diabetes controlled with diet. Developed type II diabetes at age 51: Can’t oral meds (leg swelling [Actos, Avandia], lactic acid buildup with metformin, etc.). Was put on Lantus 2 years ago…done well until this fall when I became ill with aspergillus fungal ball in left maxially sinus with Actiomycosis. Was told diabetes was a problem, but my A1C was 6.5 on admission.

    Was Discharged on 18 units of Lantus was (was on 12 on admission) and Novalog on a sliding scale. Just about 4 months later, they have me on 48 units of Lantus – which was changed to Levemir last week due to horrible leg selling with great difficulty walking, 10 lbs weight gain. One week on Levemir, I have the same problem with the legs and weight has not moved. Morning fasting numbers are going higher.

    It seems that the more insulin they have me take, the greater the fasting numbers are in the morning. My A1C’s are now 7.2 and I’m afraid to eat anything.

    Any suggestions?

  • Confused and Frustrated

    I forgot to note that prior to the almost deadly infection, I lost 40 lbs on a high protein diet through a weight loss company and was able to stop the Lantus. As part of the vitamin protocol, they had me take chromium 4 times a day – 200 mg, plus magnesium, nulti-vitiamin and potassium/sodium tablets as needed due to the high water intake and my AiC was a firm/constant 6.5.

    My diabetic MD won’t let me take the chromium and insists in the high insulin intake.

  • Katie

    I have been on the pump now for a little over a year. I was diagnosed with type 1 diabetes 11 years ago. Origonally I was on lantus and humalog. When I went to the pump, my endo put me on Apidra. Since then, my A1c is much better, however I have horrible swelling in my legs and feet. No one seems to know why. I’ve been to a kidney specialist who put me on lasiks, and gave me lisinopril (kidney protector). Does anyone know if it could be the Apidra that is making my legs swell up? Is there something I should be trying that doctors haven’t shared with me yet?! HELP!