Category Archives: Drugs for Diabetes

Pioglitazone and Bladder Cancer

MedPage Today reports that another study links pioglitazone with bladder cancer in the U.K.  I’m not sure how the U.S. Food and Drug Administration will react to this.

We have 11 classes of drugs for treatment of diabetes.  Thiazolidinediones, aka glitazones or TZDs, are one class.  Pioglitazone and rosiglitazone are the only two drugs in the class, at least in the U.S.  Rosiglitazone is already highly restricted due to concern about heart toxicity.

This latest news confirms my inclination to treat type 2 diabetes with weight management, exercise, and a low-carbohydrate diet, when able.

Steve Parker, M.D.

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Hot Off the Press: New ADA Hyperglycemia Management Guidelines

I’ll get to the following article when time allows.  It’s in a June, 2012, issue of Diabetes Care.  (Didn’t they publish management principles just six months ago?  Jeez.)

Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach:  Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

-Steve

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Bladder Cancer Linked With Diabetes Drugs in Thiazolidinedione Class

MedPage Today reports that thiazolidinediones (aka glitazones) are linked to development of bladder cancer.  Pioglitazone is the most commonly used TZD in the U.S.  From the article:

The increased risk of bladder cancer associated with glitazones — which reached a relative increase of 72% in patients who started on the agents more than 5 years earlier — “appears to be a class effect,” the research team, led by Ronac Mamtani, MD, of the University of Pennsylvania in Philadelphia, concluded.

According to the National Cancer Institute, the U.S. has 74,000 new cases of bladder cancer yearly, and 15,000 annual deaths from bladder cancer.

If you take a thiazolidinedione, talk to your doctor about bladder cancer at your next visit.

Steve Parker, M.D.

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Latest Research: 1) Sleep Patterns and Diabetes, 2) Drop Metformin When You Start Insulin?

1) Lack of sleep coupled with disrupted day-night cycles predisposes to diabetes and prediabetes.  Night-shift workers take note.

2) Compared to those using metformin alone, type 2 diabetics who also took insulin needed less insulin and had better blood sugar levels.  Real-world benefits are not entirely clear.

Steve Parker, M.D. 

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Random Thoughts On Paleo Eating for People With Diabetes

Not really pertinent, but I like buffalo

I was interviewed a couple months ago by Amy Stockwell Mercer, author of Smart Woman’s Guide to Diabetes. All I knew beforehand was that she was interested in my thoughts on the paleo diet as applied to diabetes.  I think she had run across my PaleoDiabetic blog.

In preparation, I collected some random thoughts and did a little research.

What’s the paleo diet?

Fresh, minimally processed food. Meat (lean or not? supermarket vs yuppiefied?), poultry, eggs, fish, leafy greens and other vegetables, nuts, berries, fruit, and probably tubers.

Non-paleo: highly processed, grains, refined sugars, industrial plant/seed oils, legumes, milk, cheese, yogurt.

The paleo diet is also called Old Stone Age, caveman, ancestral, hunter-gatherer, and Paleolithic diet.

Is the paleo diet deficient in any nutrients?

A quick scan of Loren Cordain’s website found mention of possible calcium and vitamin D deficits. Paleoistas will get vitamin D via sun exposure and fish (especially cold-water fatty fish). Obtain calcium from broccoli, kale, sardines, almonds, collards. (I wonder if the Recommended Dietary Allowance for calcium is set too high.)

What About Carbohydrates and Diabetes and the Paleo Diet?

Diabetes is a disorder of carbohydrate metabolism. In a way, it’s an intolerance of carbohydrates. In type 1 diabetes, there’s a total or near-total lack of insulin production on an autoimmune basis. In type 2 diabetes, the body’s insulin just isn’t working adequately; insulin production can be high, normal or low. In both cases, ingested carboydrates can’t be processed in a normal healthy way, so they stack up in the bloodstream as high blood sugars. If not addressed adequately, high blood glucose levels sooner or later will poison body tissues . Sooner in type 1, later in type 2. (Yes, this is a gross over-simplification.)

Gluten-rich Neolithic food

If you’re intolerant of lactose or gluten, you avoid those. If you’re intolerant of carbohydrates, you could avoid eating them, or take drugs to help you overcome your intolerance. Type 1 diabetics must take insulin. Insulin’s more optional for type 2’s. We have 11 classes of drugs to treat type 2 diabetes; we don’t know the potential adverse effects of most of these drugs. Already, three diabetes drugs have been taken off the U.S. market or severely restricted due to unacceptable toxicity: phenformin, troglitazone, and rosiglitazone.

Humans need two “essential fatty acids” and nine “essential” amino acids derived from proteins. “Essential” means we can’t be healthy and live long without them. Our bodies can’t synthesize them. On the other hand, there are no essential carbohydrates. Our bodies can make all the carbohydrate (mainly glucose) we need.

Since there are no essential carbohydrates, and we know little about the long-term adverse side effects of many of the diabetes drugs, I favor carbohydrate restriction for people with carboydrate intolerance. (To be clear, insulin is safe, indeed life-saving, for those with type 1 diabetes.)

That being said, let’s think about the Standard American Diet (SAD) eaten by an adult. It provides an average of 2673 calories a day. Added sugars provide 459 of those calories, or 17% o the total. Grains provide 625 calories, or 23% of the total. And most of those sugars and grains are in processed, commercial foods. So added sugars and grains provide 40% of the total calories in the SAD. (Figures are from an April 5, 2011, infographic at Civil Eats.)

Anyone going from the SAD to pure Paleo eating will be drastically reducing intake of added sugars and grains, our current major sources of carbohydrate. Question is, what will they replace those calories with?

That’s why I gave a thumbnail sketch of the paleo diet above. Take a gander and you’ll see lots of low-carb and no-carb options, along with some carb options. For folks with carbohydrate intolerance, I’d favor lower-carb veggies and judicious amounts of fruits, berries, and higher-carb veggies and

Will these cause bladder cancer? Pancreatitis?

tubers. “Judicious” depends on the individual, considering factors such as degree of residual insulin production, insulin sensitivity, the need to lose excess weight, and desire to avoid diabetes drugs.

Compared to the standard “diabetic diet” (what’s that?) and the Standard American Diet, switching to paleo should lower the glycemic index and glycemic load of the diet. Theoretically, that should help with blood sugar control.

A well-designed low-carb paleo diet would likely have at least twice as much fiber as the typical American diet, which would also tend to limit high blood sugar excursions.

In general, I favor a carbohydrate-restricted paleo diet for those with diabetes who have already decided to “go paleo.” I’m not endorsing any paleo diet for anyone with diabetes at this point—I’m still doing my research. But if you’re going to do it, I’d keep it lower-carb.  E.g., under 100 g of digestible carb daily. It has a lot of potential.

Are There Any Immediate Dangers for a Person With Diabetes Switching to the Paleo Diet?

It depends on three things: 1) current diet, and 2) current drug therapy, and 3) the particular version of paleo diet followed.

Remember, the Standard American Diet provides 40% of total calories as added sugars and grains (nearly all highly refined). Switching from SAD to a low-carb paleo diet will cut carb intake and glycemic load substantially, raising the risk of hypoglycemia if the person is taking certain drugs.

Drugs with potential to cause hypoglycemia include insulin, sulfonylureas, meglitinides, pramlintide, and perhaps thiazolidinediones.

Who knows about carb content of the standard “diabetic diet”? Contrary to poplular belief, there is no monolithic “diabetic diet.” There is no ADA diet (American Diabetes Association). My impression, however, is that the ADA favors relatively high carbohydrate consumption, perhaps 45-60% of total calories. Switching to low-carb paleo could definitely cause hypoglycemia in those taking the aforementioned drugs.

One way to avoid diet-induced hypoglycemia is to reduce the diabetic drug dose.

A type 2 overweight diabetic eating a Standard American Diet—and I know there are many out there—would tend to see lower glucose levels by switching to probably any of the popular paleo diets. Be ready for hypoglycemia if you take those drugs.

Paleo diets are not necessarily low-carb. Konner and Eaton estimate that ancestral hunter-gatherers obtained 35 to 40% of total calories from carbohydrates. I’ve seen other estimates as low as 22%. Reality likely falls between 22 and 65%. When pressed for a brief answer as to how many carbohydrate calories are in the paleo diet, I say “about a third of the total.” By comparison, the typical U.S. diet provides 50% of calories from carbohydrate.

Someone could end up with a high-carb paleo diet easily, by emphasizing tubers (e.g., potatoes), higher-carb vegetables, fruits, berries, and nuts (especially cashews). Compared with the SAD, this could cause higher or lower blood sugars, or no net change.

A diabetic on a Bernstein-style diet or Ketogenic Mediterranean Diet (both very-low-carb) but switching to paleo or low-carb paleo (50-150 g?) would see elevated blood sugars. Perhaps dangerously high glucoses.

Any person with diabetes making a change in diet should do it in consultation with a personal physician or other qualified healthcare professional familiar with their case.

Steve Parker, M.D.

Fun Facts!

  • A typical carbonated soda contain the equivalent of 10 tsp (50 ml) of sugar.
  • The typical U.S. adult eats 30 tsp (150 ml) daily of added sweeteners and sugars.
  • U.S total grain product consumption was at record lows in the 1970s, at 138 pounds per person. By 2000, grain consumption was up by 45%, to 200 pounds per person.
  • Total caloric sweetener consumption (by dry weight) was 110 pounds per person in the 1950s. By 2000, it was up 39% to 150 pounds.
  • Between 1970 and 2003, consumption of added fats and oils rose by 63%, from 53 to 85 pounds. [How tasty would that be without starches and sugars? Not very.]
  • In 2008, “added fat” calories in the U.S. adult diet were 641 (24% of total calories).

Fun Facts provided by the U.S. Department of Agriculture.

 

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Filed under Carbohydrate, Dairy Products, Drugs for Diabetes, Fat in Diet, Glycemic Index and Load, Grains, Paleo diet

Eliminate Diabetes Drugs By Eating Right

Jimmy Moore has posted a podcast interview with internist Luan Pho, who thinks that the right diet can help reduce or eliminate usage of diabetic drugs.  I’m sure involves type 2 diabetes, not type 1.  I haven’t listened to the podcast, but you may want to.

-Steve

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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 PhysiciansAnnals of Internal Medicine, 156 (2012): 218-231.

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Metformin May Prevent Cancer and Heart Trouble

David Spero at Diabetes Self-Management has an interesting article about how metformin may prevent cancer and heart disease, and slow the aging process.  Metformin is the usual first drug of choice for type 2 diabetes.

Steve Parker, M.D.

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Your Tax Dollars At Work: FDA Warns HCG Marketers

 

"It's been three months. That HCG should kick in right about now."

Ooooh!  I’m sure they’re shaking in their boots.

I ran across a patient in the emergency department a couple months ago who coincidentally happened to be taking over-the-counter HCG oral drops for help with weight loss.  She didn’t ask my opinion, so I didn’t give it.

Now the FDA has sent a stern warning letter to seven HCG diet marketers to cease and desist.  I started seeing ads for homeopathic oral HCG at least a year ago.  And the FDA is just now getting around to the letters?

The Science-Based Medicine blog can teach you about homeopathy.

Here’s a snippet from the first FDA link above:

Miller explains that HCG was first promoted for weight loss in the 1950s. “It faded in the 1970s, especially when it became apparent that there was a lack of evidence to support the use of HCG for weight loss,” she says.

The diet has become popular again and FDA and FTC are taking action on illegal HCG products. “You cannot sell products claiming to contain HCG as an OTC drug product. It’s illegal,” says Brad Pace, team leader and regulatory counsel at FDA’s Health Fraud and Consumer Outreach Branch. “If these companies don’t heed our warnings, they could face enforcement actions, legal penalties or criminal prosecution.” 

You think these HCG marketers didn’t know from the git-go that what they were doing was illegal?

I’d have thought the FDA already had enough poop to start enforcement actions.

But what do I know?

Steve Parker, M.D.

 

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What About Insulin Pumps?

Ever wonder what it’s like to get your insulin via a pump?  Tim at Shoot Up or Put Up shares his year’s worth of pump experience with the world.  Tim must have type 1 diabetes. He lives in the U.K., so you’ll see blood sugar levels in mmol/l instead of the U.S. standard of mg/dl.  To convert mmol/l to mg/dl, multiply by 18.

Steve Parker, M.D.

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