Tag Archives: Drugs for Diabetes

August 12, 2016 · 2:00 AM

Introducing Tresiba (insulin degludec): a New Long-Acting Basal Insulin

Tresiba joins other long-acting insulins like insulin glargine (Lantus), insulin detemir (Levemir), and good ol’ NPH insulin. It was approved by the U.S. Food and Drug Administration this year; it’s been used in other countries for longer. Insulin degludec will have different names depending on the country.

Who Is It For?

  • Adults with type 1 and 2 diabetes
  • Not for diabetic ketoacidosis
  • We have no good data on use in children (under 18), pregnant women, and nursing mothers

How Long Does It Work?

It will last for at least 30 hours in most users. After that, effectiveness starts to taper off but some effect may be seen as long as 42 hours after the injection.

What Is Its Role In Treating Diabetes?

Insulin degludec is a basal insulin, meaning that it runs in the background continuously. It’s not designed to reduce blood sugar that rises after a meal. If your pancreas still makes insulin, release of that insulin may reduce after-meal glucose levels adequately. Otherwise, after-meal glucose elevations are addressed with bolus insulin injections. Bolus-type insulins are the rapid-acting ones like Humalog and Novolog.

Most NPH insulin users, and some insulin glargine (Lantus) users, need the injection twice daily. Because of its long duration of action, Triseba users should never need more than one injection daily. I don’t have much experience with Levemir because the hospital where I work doesn’t stock it.

Triseba users should take it at about the same time daily. If you miss that time by up to five or six hours either way, it probably won’t matter.

What’s the Dose?

For type 2 diabetics who have never used insulin, the starting dose is typically 10 units/day.

For type 1’s switching from other insulins, the usual starting dose is one-third to one-half of the total daily insulin dose, plus rapid-acting bolus insulin around meal times for the remainder.

Change the dose no more often than every three or four days.

How Much Does It Cost?

I don’t know. Likely more than some of the other basal insulins.

Steve Parker, M.D.

PS: Click here for full prescribing information.

PPS: If words like glargine, degludec, and detemir turn your stomach, you’ll appreciate my book.

You'll not find "degludec" in here

You’ll not find “degludec” in here

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June 23, 2016 · 2:00 AM

Are These Two Diabetes Drugs Better Than the Others?

Better living through chemistry

Empagliflozin is a pill. Liraglutide is a once-daily subQ injection.

The two drugs in question are empagliflozin (aka Jardiance) and liraglutide (aka Victoza). Both are used to treat type 2 diabetes, not type 1.

A major problem we have with most diabetes drugs is that while they do lower blood sugars, we don’t have much evidence on whether they actually prolong life and prevent bad outcomes like heart attacks, strokes, cancer, blindness, kidney failure, amputations, and serious infections. It gets even more complicated. For instance, a given drug may eventually be proven to prolong life by a year via prevention of death from heart disease, while at the same time increasing the risk of spending that last year bedridden from a stroke.

It’s extremely difficult and costly to suss out these issues. It requires large clinical trials wherein half of the PWDs (people with diabetes) are treated with a particular drug, and the other half are treated with “standard therapy.” Five or 10 years later you compare clinical endpoints between the two groups. A couple studies have done this recently.

A blogger I follow, Larry Husten, wrote the following:

But it was the secondary goal of these trials that led to the transformation of the field. Baked into the trial design was the provision that if they were able to establish noninferiority then the trial investigators were permitted to test for superiority. The second phase began when Empa-Reg became the first trial to convincingly show a clear benefit, including a reduction in cardiovascular death and a reduction in hospitalization for heart failure. with empagliflozin (Jardiance, Merck). Then, more recently, the LEADER trial showed a significant reduction in cardiovascular events with liraglutide (Victoza, Novo Nordisk). In both trials nearly all the patients had significant established cardiovascular disease—precisely the population that cardiologists are likely to see.

Click the embedded links above for more details. Even better, read the original research reports if you have the time and knowledge. I support my family with a full-time job taking care of patients, so it will be a while (if ever) before I can dig into this further. (When my book sales make me independently wealthy, I’ll have more time for this!)

diabetic diet, low-carb Mediterranean Diet, low-carb, Conquer Diabetes and Prediabetes

Analyzing clinical reports requires a good grasp of logic, statistics, and basic science

Are the LEADER and Empa-Reg trials valid? Yeah, maybe. In an ideal world, other investigators would try to replicate the results with additional clinical trials. Are the published results free of fraud and bias? I don’t know.

Because we don’t know the long-term effects of many of our diabetes drugs, I favor doing as much as possible to control blood sugars with diet, exercise, and weight management.

Stay tuned for future developments.

Steve Parker, M.D.

PS: Just because one drug in a class of drugs reduces bad clinical outcomes, it doesn’t mean all drugs in the class do.

PPS: If it’s hard for you to pronounce empagliflozin and liraglutide, some of my books don’t even have them.

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February 3, 2016 · 6:12 PM

Which Diabetes Drugs Cause Hypoglycemia?

Hypoglycemia—aka low blood sugar—can kill you. The most common cause is medications taken by people with diabetes.

DRUGS THAT RARELY, IF EVER, CAUSE HYPOGLYCEMIA

Diabetics not being treated with pills or insulin rarely need to worry about hypoglycemia. That’s usually true also for prediabetics. Yes, some type 2 diabetics control their condition with diet and exercise alone, without drugs.

Similarly, diabetics treated only with diet, metformin, colesevalam, sodium-glucose co-transport 2 inhibitor (SGLT2 inhibitor), and/or an alpha-glucosidase inhibitor (acarbose, miglitol) should not have much, if any, trouble with hypoglycemia. The DPP4-inhibitors (sitagliptan and saxagliptin) do not seem to cause low glucose levels, whether used alone or combined with metformin or a thiazoladinedione. Thiazolidinediones by themselves cause hypoglycemia in only 1 to 3% of users, but might cause a higher percentage in people on a reduced calorie diet. Bromocriptine may slightly increase the risk of hypoglycemia. GLP-1 analogues rarely cause hypoglycemia, but they can.

DRUGS THAT CAUSE HYPOGLYCEMIA

Regardless of diet, diabetics are at risk for hypoglycemia if they use any of the following drug classes. Also listed are a few of the individual drugs in some classes:

  • insulins
  • sulfonylureas: glipizide, glyburide, glimiperide, chlorpropamide, acetohexamide, tolbutamide
  • meglitinides: repaglinide, nateglinide
  • pramlintide plus insulin
  • possibly GLP-1 analogues
  • GLP-1 analogues (exanatide, liragultide, albiglutide, dulaglutide) when used with insulin, sufonylureas, or meglitinides
  • possibly thiazolidinediones: pioglitazone, rosiglitazone
  • possibly bromocriptine

BECOME THE EXPERT ON YOUR OWN DRUGS

If you take drugs for diabetes, you need to be your own pharmaceutical expert. Don’t depend solely on your physician or pharmacist. Your doctor has to be familiar with 150–200 drugs, and the pharmacist, even more. You only need to master two or three, I hope. Here are important things to know about your drugs:

  • interactions with other drugs or supplements you take, whether prescription or over-the-counter
  • how to monitor for drug toxicity (e.g., periodic blood tests)
  • potential adverse effects
  • is the money-saving generic just as good as the brand-name drug
  • what’s the maximum dose and how often can the dose be adjusted
  • if you take a brand-name drug, what’s the generic name

Steve Parker, M.D.

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Front cover of book

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December 6, 2015 · 5:41 AM

Does Big Pharma Have Too Much Influence on Diabetes Management?

diabetic mediterranean diet, Steve Parker MD

“For this, I needed six years of college?!”

MedPageToday has a series of articles looking at socioeconomic issues related to diabetes drugs that have come onto the market in the last decade. They call it their Diabetes Drugs Investigation. I recommend the entire series to you if you have type 2 diabetes. The authors’ have five major points:

1. “Diabetes drugs improve lab tests, but not much more, particularly in pre-diabetics.” FDA drug approvals were based mostly on whether hemoglobin A1c or blood sugar levels improved, not on improvements in hard clinical endpoints such as risk of death, heart attacks, stroke, blindness, amputations, etc.

2. “Physicians and drug makers have reported diabetes drugs as the “primary suspect” in thousands of deaths and hospitalizations.”

3. “Diabetes drug makers paid physicians on influential panels millions of dollars.” The implication is that the panelists were not totally unbiased in their assessments of drug effectiveness and safety.

4. “Risk of a risk now equals disease.” This is about the latest redefinition of prediabetes which created many more “patients.” Prediabetes can progress to type 2 diabetes over a number of years: one of every four adults with prediabetes develops diabetes over the next 3 to 5 years. Some doctors are even treating prediabetes with diabetic drugs. (I recommend a “diet and exercise” approach.) The authors think the prediabetic label—one third of U.S. adults, including half of all folks over 65—is over-used and over-treated.

5. “The clinical threshold for diagnosing diabetes has crept lower and lower over the past decade.” For instance, in 1997 expert panels lowered the threshold defining diabetes from a fasting blood glucose level of 140 mg/dl (7.8 mmol/l) to 125 mg/dl (6.9 mmol/l). Four million more American adults became diabetics overnight. In 2003, they lowered the threshold for prediabetes from a fasting blood glucose from 110 mg/dl (6.1 mmol/l) to 100 mg/dl (5.6 mmol/l). Boom! 46 million more American prediabetics.

I fully agree with the authors that we don’t know which drugs for type 2 diabetes are the best in terms of prolonging life, preventing diabetes complications, and postponing heart attacks and strokes. Furthermore, we don’t know all the adverse long-term effects of most of these drugs. For instance, metformin had been on the market for over a decade before we figured out it’s linked to vitamin B12 deficiency. That’s why I try to convince my patients to do as much as they can, when able, with diet and exercise before resorting to one or more drugs. (All type 1 diabetics and a minority of type 2 diabetics must take insulin.) Maybe it’s healthier to focus primarily on drug therapy…but I don’t think so.

RTWT.

Steve Parker, M.D.

low-carb mediterranean diet

Front cover of book

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November 20, 2015 · 2:00 AM

What’s Wrong With Drugs for Diabetes?

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How about this one?

MedPageToday has an article on the “Bittersweet Diabetes Economy” talking about the cost of treating diabetes, Big Pharma influence on diagnosis and treatment of diabetes and prediabetes, and the unknown long-term effectiveness of diabetes drugs. Most of the article pertains to type 2 diabetes. A quote:

Last year, sales of diabetes drugs reached $23 billion [worldwide or U.S.?], according to the data from IMS Health, a drug market research firm. That was more than the combined revenue of the National Football League, Major League Baseball, and the National Basketball Association.

But from 2004 to 2013, none of the 30 new diabetes drugs that came on the market were proven to improve key outcomes, such as reducing heart attacks or strokes, blindness, or other complications of the disease, an investigation by MedPage Today and the Milwaukee Journal Sentinel found.

The U.S. Food and Drug Administration approved all of those drugs based on a surrogate endpoint: the ability to lower blood sugar. Many of the new drugs have dubious benefit; some can be harmful.

Another key outcome we don’t know about is prevention or postponement of death via drug therapy for type 2 diabetes.

Now you have some inkling of why I exhort my patients to maximize diet and exercise interventions before resorting to drugs, increasing drug dosages, or adding more drugs. (I’m not talking about type 1 diabetes here.)

RTWT.

Steve Parker, M.D.

low-carb mediterranean diet

Front cover of book

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September 29, 2014 · 5:39 AM

Narrowing Down Your Choice of Diabetes Drugs

Conquer Diabetes and Prediabetes

Metformin is the most-recommended drug for type 2 diabetes

We now have 12 classes of drugs for the treatment of diabetes. How does your doctor choose which ones to use?

It’s easy for type 1 diabetes: insulin. Type 2’s have more options.

Earlier this year I reviewed the American Diabetes Association’s Standards of Medical Care in Diabetes – 2014. A type 2 treatment algorithm therein mentions only six of the 12 classes. This gives you an idea of expert consensus on which drugs to use. The classes are biquanides (metformin), sulfonylureas, thiazolidinediones, DPP-4 inhibitors, GLP-1 agonists, and insulins. This is one reason you don’t see much use of bromocriptine and colesevelam.

The American Association of Clinical Endocrinologists also has a type 2 diabetes treatment algorithm, published in 2013. It also addresses prediabetes and overweight/obesity. You’ll see some of the other classes mentioned. You may find it confusing because of abbreviations.

Believe it or not, most doctors want to do what’s right for our patients. We want positive results that reduce suffering and death. Does Big Pharma influence the production of guidelines and individual physician drug choices? If I had to guess, I’d say yes. But I don’t have the resources to investigate that in any depth. I know without a doubt that if I recommend a drug and the patient has a bad outcome, it helps me win the malpractice lawsuit if I’ve recommended a guideline-approved drug. Other docs know that, and it’s one of many factors that influence drug choice. We also consider cost (if you bring it up), convenience, patient preference, what our local colleagues are doing, what other illnesses the patient has, potential adverse drug effects, etc. Click here for a summary of the various drug classes.

We don’t know the long-term adverse effects of many of these drugs. That’s why I favor doing as much as reasonably possible with lifestyle modification, such as diet and exercise, before stacking up multiple drugs. If you need drugs, and most with diabetes do, lifestyle modification can help you minimize drug use.

Steve Parker, M.D.

PS: My Conquer Diabetes and Prediabetes book is now available on Kindle and other digital formats.

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February 22, 2012 · 2:00 AM

Oral Drugs for Type 2 Diabetes: Which Are The Best?

A guideline committee established by the American College of Physicians recently reviewed oral medications for treatment of type 2 diabetes.  Assuming blood sugars were still too high after diet and lifestyle modification, the firmest drug recommendations were:

  • Use metformin first.
  • If blood sugars are still too high, add a second agent to metformin.

This was not nearly as helpful as I’d hoped it would be!

The Problem: Too Many Options

We now have 11 classes of drugs for treatment of 26 million diabetics in the United States.  Clinicians are often at a loss as to which drug(s) to recommend for a particular patient.  For most of these drugs, we know very little about the long-term implications, such as effects on overall death rates, diabetes complications, heart attacks, cancer, and strokes. 

I can think of three diabetes drugs once approved by the U.S. Food and Drug Administration, but are now off the market or severely restricted due to serious adverse side effects: phenformin, troglitazone (Rezulin), and rosiglitazone (Avandia).  I fully expect one or more of our current drugs will have a similar fate; only time will tell which ones.

France took pioglitazone off the shelves in 2011 because of a link with bladder cancer.  It’s still available and popular in the U.S.

When you get into multi-drug therapy with two or three different oral drugs, the situation becomes even cloudier.

Some Needles in the Haystack

I reviewed the report from the guideline committee and found just a few clinical pearls to share with you. 

  • They didn’t mention at all the FDA’s recent restrictions on rosiglitazone, so I assume they don’t believe it’s more toxic to the heart than is pioglitazone.
  • Most oral drugs reduce hemoglobin A1c by an average of 1% (absolute decrease).
  • All double-drug regimens were more effective at controlling blood sugars than monotherapy (using only one drug): adding a second drug drops hemoglobin A1c another 1%.
  • “It was difficult to draw conclusions about the comparative effectiveness of type 2 diabetes medications on all-cause mortality, cardiovascular morbidity and mortality, and microvascular outcomes because of low quality or insufficient evidence.”  It was so difficult that they didn’t draw any firm conclusions.  In other words, in terms of overall deaths , heart attacks, heart failure, and strokes, it’s hard to favor some of these drugs over others.  However…
  • Compared to sulfonylureas, metformin was linked to a  lower overall death rate and cardiovascular illness (e.g., heart attacks, heart failure, angina).
  • Sulfonylureas and meglitinides tend to cause more hypoglycemia.
  • Thiazolidinediones are linked to a higher risk of heart failure; they shouldn’t be used in patients who already have serious heart failure.
  • Thiazolidinediones may increase the risk of bone fractures.
  • Metformin helps with loss of excess weight, reduces LDL (bad) cholesterol, and lowers triglycerides.
  • Metformin is cheaper than most other diabetes drugs.
  • For double-drug therapy: “No good evidence supports one combination therapy over another, even though some evidence shows that the combination of metformin with another agent generally tends to have better efficacy [better blood sugar control] than any other monotherapy or combination therapy.”

In contrast to these guidelines, the American Association of Clinical Endocrinology guidelines of  2009  recommend that  the following should be used earlier and more frequently:  GLP-1 agonists (exenatide) and DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin).  Furthermore, sulfonylureas should have a lower priority than in the past. From my limited perspective here in the Sonoran desert, I have no way of knowing how much influence, if any, Big Pharma had over the AACE guidlelines.

My concern about long-term safety of some these drugs compels me to favor carbohydrate restriction, which reduces the overall need for drugs.  Sure, that’s not true for everybody and it may not last forever.  The more carbs you eat, the more drugs you’re likely to need to keep blood sugars in control in an effort to avoid diabetes complications.

Don’t get me wrong; I’m not anti-drug.  As an internist, I prescribe plenty of drugs every day.  They are a major weapon in my armamentarium.  Regardless of the condition I’m treating, I always try to avoid drugs with unknown and potentially serious long-term consequences.

Steve Parker, M.D.

Reference: Qaseem, Amir, et al.  Oral pharmacologic treatment of type 2 diabetes mellitus: A clinical practice guideline from the American College of Physicians.  Annals of Internal Medicine, 156 (2012): 218-231.

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November 5, 2011 · 2:00 AM

Drug Review: GLP-1 Analogues (exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide)

GLP-1 analogues available in the U.S. are exenatide (sold as Byetta and Bydureon), liraglutide (sold as Victoza), albiglutide (Tanzeum), dulaglutide (Trulicity), and lixisenatide (Adlyxin).  They are sometimes referred to as GLP-1 receptor agonists.  They are not considered first-choice drugs, but instead are typically used in combination with other drugs, in conjuction with diet and exercise.

Remember that drug names vary by country and manufacturer.  This is a brief review only; consult your physician or pharmacist for full details.

Fun Fact for the diabetic version of  Trivial Pursuit:

Exenatide  (Byetta and Bydureon) is a synthesized version of a protein initially discovered in the saliva of a lizard, the Gila monster.

How do they work?

It’s complicated.

First off, you need to know that a small intestine hormone, glucagon-like peptide-1 (GLP-1), is produced in response to a meal.  This hormone increases insulin secretion by pancreas beta cells, suppresses glucagon after meals, inhibits emptying of the stomach, and inhibits appetite. Other effects are suppression of glucose production by the liver, and improved glucose uptake by tissues outside the liver.  All this tends to lower blood sugar levels after meals.

The problem is that GLP-1 is quickly destroyed by an enzyme called DPP-4.  We have available to us now chemicals similar to GLP-1, called GLP-1 analogues, that bind to the GLP-1 receptors and are resistant to degradation by the enzyme DPP-4.  They essentially act like GLP-1, and they hang around longer.

GLP-1 levels, by the way, are decreased in type 2 diabetes.

The action of GLP-1 is dependent on blood sugar levels.  If blood glucose is not elevated, GLP-1 doesn’t go to work.  From a practical viewpoint, this means that GLP-1-based therapies rarely cause hypoglycemia.

We know little about long-term outcomes with these drugs, such as diabetic complications, health-related quality of life, or mortality.

Uses

Exenatide (Byetta)  is FDA-approved for adults with type 2 diabetes who are not adequately controlled with metformin, sulfonylurea, or a thiazolidinedione (or a combination of these agents).  So it’s an add-on drug, not approved for use by itself.  In October, 2011, the FDA extended approval as an add-on therapy to insulin glargine (for example, Lantus in the U.S.), with or without metformin and/or a thiazolidinedione (TZD), in conjunction with diet and exercise for adults with type 2 diabetes who are not achieving adequate glycemic control on insulin glargine alone.

Once-weely exenatide (Bydureon) was FDA-approved in January, 2012.  Use with insulin has not been studied and is not recommended.  Don’t use along with Byetta.  Surprisingly, I found nothing in the drug package insert Feb.2, 2012, regarding whether it can be used with other diabetes drugs.  See comments in the preceding paragraph regarding standard twice-daily exenatide.  I suspect Bydureon can be used with metformin, sulfonylurea, thiazolidinedione, and insulin glargine (Lantus), but the package insert is not at all clear.

Liraglutide is FDA-approved for treatment of type 2 diabetes but is not recommended as initial therapy, although it does seem to be approved for use by itself.  It has been used alone and also in combination with metformin, sulfonylurea, and/or thiazolidinediones.  It’s not approved for use with insulin therapy.

Albiglutide is a once-weekly subcutaneous injection for type 2 diabetes. It was FDA-approved in 2014. It’s not recommended as initial drug therapy, although it is approved for use by itself. It can be used in combination with metformin, sulfonylurea, thiazolidinediones, and/or insulin.

Dulaglutide is also a once-weekly injection for adults with type 2 diabetes, approved by the FDA in2014.  It’s not a first-line drug, but can be used by itself or with metformin, glimiperide (and presumably other sulfonylureas), pioglitazone, and insulin lisper (e.g., Humalog, a rapid-acting insulin).

Lixisenatide is a daily injection for adults with type 2 diabetes. It can be used alone or in combination with metformin, sulfonylurea, thiazolidinedione (e.g., pioglitazone), or long-acting insulin (insulin glargine). Clinical trials did not include short-acting insulin.

You can assume none of these have been tested for safety in pregnant or nursing mothers.

Dosing

They are available only as subcutaneous injections.  Exenatide is twice daily, starting at 5 mcg within 60 minutes prior to a meal.  After one month, the dose may be increased to 10 mcg twice daily.

Extended-release exenatide (Bydureon): 2 mg subcutaneous injection every seven days.

Liraglutide is a once daily subcutaneous injection starting at 0.6 mg, increasing to 1.2 mg after one week.  It is given without regard to meals.  Maximum dose is 1.8 mg/day.

Albiglutide is started at 30 mg subcutaneously every seven days and may be increased to 50 mg if needed.

Start dulaglutide at 0.75 mg weekly, increasing to 1.5 mg weekly if needed.

Lixisenatide starts at 10 mcg daily for 14 days then increases to 20 mcg daily.

Side Effects

GLP-1 analogues tend to cause nausea, vomiting, and diarrhea in as many as four in 10 users.  The nausea typically improves over time.  Compared with Byetta, Bydureon seems to cause less nausea.  They tend to cause weight loss.  These drugs might cause pancreatitis, which is life-threatening.  When used with insulin or an insulin secretagogue (like sulfonylureas or meglitinides), hypoglycemia may occur.

Hypoglycemia is rare when GLP-1 analogues are used as the sole diabetes drug, but still possible (0-5% risk?). When it happens, it’s rarely severe.

Liraglutide, albiglutide, and dulaglutide might cause thyroid cancer or thyroid tumors.   

Don’t use if you have . . .

… severe kidney impairment (exenatide), end-stage renal disease (lixisenatide),Multiple Endocrine Neoplasia syndrome (liraglutide), Multiple Endocrine Neoplasia syndrome type 2 (albiglutide, dulaglutide), or family history of medullary thyroid cancer (liraglutide, albiglutide, dulaglutide), or personal history or medullary thyroid cancer (albiglutide, dulaglutide).

Use GLP-1 analogues with caution or avoid entirely if you have a history of pancreatitis or gastroparesis. Don’t use dulaglutide if you have pre-existing severe gastrointestinal disease.

Use liraglutide with caution in patients with kidney or liver impairment. Dulaglutide is risky in the setting of liver impairment.

Don’t use any of these to treat diabetic ketoacidosis.

Steve Parker, M.D.

Last modification date: July 29, 2016

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September 15, 2010 · 2:00 AM

Drug Review: Insulin

Insulin is life-saving for type 1 diabetics.  Many type 2 diabetics will eventually, if not at the outset, need to take insulin for adequate control of blood sugars, which should help prevent diabetes complications.

My comments here are simply a brief review of insulins used by type 2 diabetics.  Anyone taking insulin must work closely with a physician or diabetes nurse educator on proper dosing, injection technique, and recognition and management of hypoglycemia (low blood sugar).

This is NOT an insulin rig! Modern insulin injections barely hurt, if at all.

Insulin’s Mechanism of Action
 

 

 

Insulin is made by the pancreas to keep blood sugars from rising above a fairly strict range: 70-140 mg/dl or 3.89-7.78 mmol/l.  [It has many other actions that I won’t bother to outline here.]  When we eat a meal containing carbohydrates (and proteins to a lesser extent), blood sugar starts to rise as we digest the carbs.  Insulin drives the sugar into our body’s cells for use as immediate energy or conversion to fat as stored energy.  About half of the insulin produced by a healthy body is “basal,” meaning it’s secreted into the bloodstream in a steady, low-volume amount, to keep the liver from making too much sugar (glucose) and controlling fasting sugar levels.  The other half is secreted in to the bloodstream in response to meals.

In type 2 diabetes, the body’s tissues, at first, are resistant to the effect of insulin.  So the pancreas has to secrete more than usual (hyperinsulinism). As the illness progresses, the pancreas cannot keep up with demand for more insulin and starts to “burn out,” producing less insulin.  This is when many type 2 diabetics need to start insulin injections.  [These are generalities; there are exceptions.]

Types of Insulin

Specific names of insulins vary by manufacturer and by country.  By convention, I capitalize only the brand names below, plus NPH and NPL.

We could break them down into two types: human (identical in structure to human insulin) and analogs (minor molecular modifications to the usual human insulin molecule).  But most people don’t care about that.  It’s more helpful to distinguish them by the timing of their action:

  • Rapid acting:  lispro (e.g., Humalog), aspart (e.g., Novolog), glulisine (e.g., Apidra)
  • Short acting:  regular (e.g., Novolin R, Humulin R)
  • Intermediate to long acting:  NPH, glargine (e.g., Lantus), detemir (e.g., Levemir), degludec (e.g., Tresiba), NPL (neutral protamine lispro)

Rapid-acting insulins have onset of action between 5 and 15 minutes, peak effect in 30 to 90 minutes, and duration of action of 2 to 4 hours.

Short-acting “regular insulin” has  onset in 30 minutes, peaks in 2 to 4 hours, and works for 5 to 8 hours.

Intermediate to long-acting insulins start working in 2 hours, don’t have a well-defined peak of action, and may keep working for 20 or more hours (glargine), for 6 to 24 hours (detemir), or 30 to 42 hours (degludec).

All these times are gross approximations.  Once the insulin is injected into the fat below the skin, it has to be absorbed into the bloodstream and transported to the tissues where it does its magic.  Lots of factors affect this process. For instance, the thicker the fat tissue at the injection site, the slower the absorption.  Absorption tends to be  faster from the abdominal wall, slower from the arms, even slower from the thighs or buttocks.  Absorption can vary from day to day in an individual even when injection site and technique are identical.

As you might have guessed, the short- and rapid-acting insulins are usually injected before a meal in anticipation of blood sugar rising as food is digested.  The intermediate- and long-acting insulins imitate the healthy body’s “basal” insulin.

Manufacturers also supply premixed insulins, combining intermdiate or long-acting insulin with a short- or rapid-acting insulin.  Examples are Humalog 75/25, Humulin 70/30, and Novolog 70/30.

Dose and Selection of Insulin

See your physician or diabetes nurse educator for details.  Many type 2 diabetics get started just with an intermediate or long-acting insulin once or twice daily, with or without diabetes drugs by mouth. Nearly all type 1’s will need a long-acting “basal” insulin (one-third to one-half of their total daily insulin requirement, plus meal-time “bolus” dosing with a rapid-acting insulin. Insulin pumps are a topic for another day.

Side Effects

By far the most common and worrisome is hypoglycemia.

Steve Parker, M.D.

Last update: August 1, 2016

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April 4, 2010 · 2:00 AM

New Page Here: Drugs for Diabetes

This is the best time in history to have diabetes.  Thanks to the advancement of science, supported by the profit motive and a degree of free market economics, we now have 10 classes of drugs to help us conquer the disease. 

I recently finished a series of brief reviews on each drug class.  Click on the Drugs for Diabetes page for links to all the reviews. 

Steve Parker, M.D.

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