Category Archives: Drugs for Diabetes

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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September 7, 2014 · 5:17 AM

Sulfonylurea Diabetes Drugs Linked to Heart Disease in Women

…according to this article at Diabetes Care. The study population was the Nurses Health Study. The longer the sulfonylurea was used, the stronger the association with coronary heart disease. CHD is by far the most common cause of heart attacks. On the bright side, the drugs were not linked to stroke risk. Remember, correlation is not causation, blah, blah, blah…

I rarely start my patients on sulfonylureas these days.

Steve Parker, M.D.

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July 16, 2014 · 4:07 AM

Sitagliptin May Increase Risk of Heart Failure

JACC has the details. Sitagliptin is a DPP-4 inhibitor used to treat type 2 diabetes. It’s sold in the U.S. as Januvia. Note that the alleged higher risk of heart failure is in patients who had a history of prior heart failure. Research findings like this are not always dependable or reproducible. It bears watching, especially if you’re a heart patient.

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July 16, 2014 · 3:01 AM

Multinational Study Suggests Insulin Pump Better Than Multiple Daily Injections for Inadequatedly-Controlled Type 2 Diabetes

Lancet has the details. I’ve only read the abstract, so don’t know much about the actual research. Study subjects were sub-optimally controlled (HgbA1c of 8-12%) on multiple daily injections; that’s why they were considered for pump therapy. They were randomized to pump or continued multiple daily injections. What I can’t tell – and it matters – is whether the multiple injection group underwent changes in their management or whether they were told to “just keep doing what your were doing” (which wasn’t working well).

 

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July 5, 2014 · 5:49 AM

A New Drug for Diabetes: Afrezza

Well, it’s not really new. It’s our old friend insulin, soon to be available via inhalation with the brand name Afrezza. The U.S. Food and Drug Administration approved it in July, 2014. Click for the package insert.

Who Can Use It?

Adults with either type 1 or 2 diabetes.

Who Should Avoid It Or Not Use It?

  • those with chronic lung disease such as asthma or chronic obstructive lung disease (COPD)
  • smokers
  • pregnant or lactating women
  • those in diabetic ketoacidosis (DKA)
  • users who see a significant deterioration in lung function over time

Common Side Effects:

Hypoglycemia, cough, throat pain.

What’s the Dose?

It comes in 4 and 8 unit cartridges. See the package insert for dosing details. Afrezza is a rapid-acting insulin taken at the start of meals, so you’re looking at two or three doses a day. Type 1 diabetics still need to take a basal (long-acting) insulin once or twice daily. As far as I can tell, the type 2 diabetics in the pre-approval clinical studies were all taking one or more oral diabetic drugs in addition to the Afrezza; the inhaled insulin was an add-on drug. The average time to maximum effect of the drug is 50 minutes with the 8 unit dose; blood levels of insulin are back to baseline after three hours.

Anything Else Interesting About It?

The manufacturer recommends a test of lung function before starting the drug, to identify folks with lung disease who shouldn’t inhale insulin. The test is called spirometry or FEV-1 (forced expiratory volume in 1 second). Moreover, spirometry should be repeated six months after start of the drug, then yearly thereafter.

Another form of inhaled insulin—Exubera—was on the U.S. market in 2006 and discontinued by the manufacturer the next year. The problem may have been poor sales or a concern about lung cancer.

You can’t get it at your pharmacy yet. Maybe later this year or the next.

Steve Parker, M.D.

 

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April 17, 2014 · 5:11 AM

One More Drug for Type 2 Diabetes: Albiglutide

The U.S. Food and Drug Administration approved albiglutide for treatment of adult type 2 diabetes in mid-April, 2014. It will be sold in the U.S. as Tanzeum. It’s a once-a-week subcutaneous injection.

Albiglutide is a GLP-1 receptor agonist, joining exenatide and liraglutide in that class.

It’s not a first-line drug for diabetes. In clinical studies, it’s been used alone and with metformin, glimiperide (a sulfonylurea), pioglitazone, and insulin.

The most frequent side effects have been upper respiratory infections, diarrhea, nausea, and injection site reactions.

Steve Parker, M.D.

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January 21, 2014 · 2:56 AM

More on the New Type 2 Diabetes Drug: Dapagliflozin (Farxiga)

We have 12 classes of drugs for the war on diabetes. The latest class is SGLT2 inhibitors and the newest of these is dapagliflozin. I read the manufacturer’s package insert an updated my SGLT2 inhibitor post.

Fun Fact: Taking 10 mg/day of dapagliflozin leads to loss of blood glucose into the urinary tract to the tune of 70 grams a day.

That’s 280 calories down the drain. I suspect that cutting 70 grams of carbohydrate from your diet would have just as much effect on diabetes as do these drugs.

Steve Parker, M.D.

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January 20, 2014 · 2:00 AM

Drug Review: SGLT2 Inhibitors (Canagliflozin, Dapagliflozin, Empagliflozin)

diabetic mediterranean diet, Steve Parker MD

Pharmacist counting pills

In March, 2013, the U.S. Food and Drug Administration approved the first agent in a new class of diabetes drugs: canagliflozin. It’s sold in the U.S. as Invokana. So we now have 12 classes of drugs for treating diabetes. In January 2014 the second drug in this class was approved: dapagliflozin or Farxiga. Empagliflozin ( U.S. brand name: Jardiance) was approved in August, 2014. Ertugliflozin (U.S. brand name: Steglatro) was approved in early 2018 or so. Other SGLT2 inhibitors are in the pipeline.

This review is quite limited—consult your physician or pharmacist for full details. Remember that drug names vary by country and manufacturer. My info source is the manufacturers’ package inserts. Any of this information could change at any time.

Class

Sodium-glucose co-transport 2 inhibitors, or SGLT2 inhibitors.

How Do They Work?

Our kidneys filter glucose (sugar) out of our bloodstream, then reabsorb that glucose back into the bloodstream. (Don’t ask me why.) SGLT2 inhibitors impair that reabsorption process, allowing some glucose to be excreted in our urine. You could call it a diuretic effect. Dapagliflozin at a dose of 10 mg/day, for example, causes the urinary loss of 70 grams of glucose daily.

Usage

These drugs are for adults with type 2 diabetes, to be used in combination with diet and exercise. They can be used alone or in combination with some of the other diabetes drugs, possibly to include insulin, metformin, sulfonylureas, or pioglitazone. Dapagliflozin has also been tested in combination with sitagliptin, a DPP4-inhibitor. Clinical experience in combination with other diabetes drugs is very limited.

Dose

Canagliflozin starts at 100 mg by mouth daily, taken before the first meal of the day. Dose can be increased to 300 mg daily. Dapagliflozin dosing starts at 5 mg by mouth every morning, with or without food, and can be increased up to 10 mg once daily. Start empagliflozin at 10 mg every AM, and max out at 25 mg every AM if needed. Ertugliflozin starts at 5 mg daily and can go up to 15 mg/day.

Side Effects

The most common side effects are vaginal yeast infections (about 5% of women), urinary tract infections, and penile yeast infections (e.g., balanitis). Also noted are increased urination, and dizziness or fainting from low blood pressure after arising to stand (orthostatic hypotension). The low blood pressures are related to a diuretic effect of this class.

Hypoglycemia (low blood sugar) is quite uncommon, perhaps nonexistent, unless these drugs are used with other drugs that often cause hypoglycemia, such as insulin and insulin secretagogues like sulfonylureas.

High potassium levels may be seen with canagliflozin. All three can cause elevations of LDL cholesterol (“bad cholesterol”).

Dapagliflozin and empagliflozin may cause elevations of creatinine in the blood, a warning that kidney function may be impaired.

Canagliflozin seems to promote weight loss, which may be welcome by some. It also doubles the risk of leg and foot amputations when compared to placebo. Ertugliflozin is also linked to increased risk of lower limb amputation.

Don’t Use If You . . .

  • have diabetic ketoacidosis
  • are pregnant or planning to get pregnant
  • have advanced or severe kidney disease
  • have severe liver impairment (glomerular filtration rate under 60 ml/min/1.73 m-squared, at least for dapagliflozin)
  • have type 1 diabetes
  • are on dialysis
  • are a nursing mother
  • for dapagliflozin: active bladder cancer (and use caution if you have history of bladder cancer)

 

Update: In 2019, the FDA approved an SGLT2 inhibitor in pill form, called semaglutide and sold in the U.S. as Rybelsus.

Updated September 26, 2019

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January 8, 2014 · 7:10 PM

One More Drug Available to Treat Type 2 Diabetes: Dapagliflozin

Open wide!

Open wide!

Where do they get these names?!

The trade name in the U.S. is Farxiga. (How do you pronounce that?) In Europe and Australia they call it Forxiga. Go figure.

MedPageToday has the details. Here’s the FDA press release, which misspells dapagliflozin. Here’s the Australian package insert for full prescribing information. I can’t find the one for the U.S. This is breaking news—I’ll write more about it when I have reliable info.

This drug joins the first drug in the SGLT2 inhibitor class: Invokana (canagliflozin). We how have 12 classes of drugs for treating diabetes.

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December 27, 2013 · 2:00 AM

Which Drugs Are Being Used For Type 2 Diabetes in the U.S.?

Better living through chemistry

Better living through chemistry?

Diabetes Care recently published results of a survey covering 1997 to 2012. The focus was on T2 diabetics age 35 or older:

“Between 1997 and 2012 biguanide [metformin] use increased, from 23% … to 53% … of treatment visits. Glitazone use grew from 6% in 1997 to 41% of all visits in 2005, but declined to 16% by 2012. Since 2005, DPP-4 inhibitor [e.g., Januvia] use increased steadily, representing 21% of treatment visits by 2012. GLP-1 agonists [e.g., Byetta] accounted for 4% of treatment visits in 2012. Visits where two or more drug compounds were used increased nearly 40% from 1997 to 2012. Between 2008 and 2012, drug expenditures increased 61%, driven primarily by use of insulin glargine [e.g., Lantus] and DPP-4 inhibitors.”

We have 12 classes of drugs for the treatment of T2 diabetes now. It’s not entirely clear which ones are the best. Since the long-term side effects of many drugs are unknown, if I had T2 diabetes I’d try to limit my need for drugs by restricting my carbohydrate consumption.

Steve Parker, M.D.

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