SGLT2, A New Class of Diabetes Drugs

A new class of diabetes drug was approved in 2013. The class is SGLT2 and the brand name is Invokana with as generic name of canagliflozin. Canagliflozin is to improve glycemic control in adults with type 2 diabetes in cooperation with diet and exercise. The drug has been studied as monotherapy and in combination with other common treatments for type 2 diabetes including metformin, sulfonylurea, pioglitazone, and insulin. The manufacturer is Johnson and Johnson.

The FDA is requiring J&J to perform five post marketing studies with canagliflozin, including a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes; and a bone safety study. This is more than any previous drug and indicates the FDA is being tough on J&J.

The most common side effects include vaginal yeast and urinary tract infections which if treated early have not been difficult to manage. The FDA states that canagliflozin is not to be used to treat people with type 1 diabetes, people with diabetic ketoacidosis, or people with severe renal disease. Over 10,000 patients in clinical trials with type 2 diabetes shows that canagliflozin improved A1C levels and fasting plasma glucose levels.

SGLT2 is short for sodium-glucose co-transporter-2 inhibitors that lower blood glucose by blocking the reabsorbtion of glucose and passing it in urine. A clinical study of patients at especially high risk of cardiovascular disease showed that within the first 30 days, 13 patients taking canagliflozin suffered a major cardiovascular event compared with just one patient taking a placebo. After that, the imbalance was reversed. The drug also caused a slight increase in unhealthy LDL cholesterol.

Canagliflozin comes in 2 different pill sizes, a 100-mg tablet and a 300-mg tablet. It is recommended that patients should take it first thing in the morning before breakfast. As an analogy, I think of giving this drug a little bit like using a diuretic, because it is going to make them a little bit glycosuric (excretion of glucose in the urine) and it will have a little bit of a diuretic effect. Therefore, take it in the morning so patients don’t urinate all night long when they're getting used to it. Clinicians should start patients at 100 mg. If that dose is tolerated then up-titrate to 300 mg, and that's the dose the patient continues to take.

David Spero writing for Diabetes Self Management has an excellent discussion on SGLT2 and what he finds as concerns.   Read his blog here.

The DPP-4 Inhibitors

DPP-4 inhibitors These are medications also used to make your pancreas produce more insulin for a short period following meals. These medications also work to prevent stored glucose from being dumped from the liver into your blood stream.

You should not take this class of medications and need to talk to your doctor if you are pregnant, planning to get pregnant, or breastfeeding, you have kidney disease, you have type 1 diabetes, and if you have a condition called diabetic ketoacidosis. The side effects while not causing low blood glucose by itself, do increase if you take medications that cause low blood glucose, or insulin. Here also your doctor may advise you to take a lower dose of other diabetes medications while on Januvia. Other possible side effects include a cold, a runny nose, sore throat, or headache. If you take any of this class of medications and have kidney problems, your doctor should order blood tests to see how well your kidneys are working.

The first drug in this class — sitagliptin, manufactured by Merck and sold under the name Januvia, received FDA approval in 2006. Saxagliptin (Onglyza), another DPP-4 inhibitor, was approved in July 2009, followed by Linagliptin (Trajenta) in 2011. A number of additional DPP-4 inhibitors are currently under development.

Last month, in early September, results from the DPP-4 inhibitor cardiovascular outcomes trials SAVOR-TIMI 53 (for Bristol Myers Squibb and AstraZeneca’s Onglyza) and EXAMINE (for Takeda’s Nesina) showed that neither drug affected the risk of heart attacks, stroke, cardiovascular death, or overall death. Onglyza showed a slight increase in hospitalization for heart failure, but there was no increase in death rates as a result.

In the SAVOR and EXAMINE trials, it is reassuring that both Onglyza and Nesina showed no increased risk of pancreatitis or pancreatic cancer, reinforcing the safety profile of DPP-4 inhibitors. The possible association of incretins (DPP-4 inhibitors and GLP-1 agonists) with pancreatitis has been a hot topic in endocrinology, but this is evidence that it should not be a concern.

I would still be concerned because of the past studies on other medications that have been fabricated and I will always have this doubt about trials preformed by pharmacological manufacturers. This may be just me, but until these medications have been on the market for at 10 years, I will always have doubts.

November Calendar of Monthly Events

There are two national events in the month of November we should be promoting. The first is one that almost every one in the diabetes on line community is aware of and that is the American Diabetes Month. Most of us are also aware of World Diabetes Day on November 14; however, most organizations in the USA do not observe it as a special day. This is of course the American Diabetes Association, which not only has their own symbol but does not support World Diabetes Day. The ADA still recognizes American Diabetes Month and takes credit for any activity they can.

The other national event is PancreaticCancer Awareness Month. With all the press for GLP-1 agonists and possible pancreatic cancer, this is especially timely and needs awareness. The GPP-4 inhibitors have also been included in the discussion about potential pancreatic cancer.

Pancreatic Cancer is one of the most challenging diseases physicians face today. It responds poorly to treatment and quickly spreads to surrounding organs. This is why November is so important: to raise awareness around early detection and prevention as well as highlight current research to help find a cure for pancreatic cancer.

Purple with a purpose on November 16 each year. The symbol is at least uniform and not part of any other organization.

Most cases of pancreatic cancer begin in the cells that produce digestive juices, called exocrine pancreas cells. These cells are located in the head of the pancreas. Other pancreatic tumors begin in the islet or endocrine cells. Early diagnosis and early intervention is the best way to beat Pancreatic Cancer. New York–Presbyterian offers the evaluative expertise to identify early and create the best treatment plan for the most successful outcomes.

New York-Presbyterian specialists are experienced in diagnosing and treating pancreatic cancer. An interdisciplinary team of gastrointestinal specialists in endoscopy, radiology, and surgery work together as a team to provide each patient with coordinated, advanced, and individualized care. New York-Presbyterian offers minimally invasive interventional endoscopic techniques to treat pancreatic cancer and it's symptoms.

Oral Diabetes Medications – Mixed Medications

Part 3 of 3 parts

I have not covered the mixed medications before, but I need to. There is no class for these medications, but there are brand names and generic names. Normally two classes are used to make up these mixed oral medications - also know as combination diabetes pills.

The first one is Actoplus Met, which is pioglitazone plus metformin. The second is a continuation of the first, which is Actoplus Met XR or long acting. The third is Avandamet, which is rosiglitazone plus metformin. I am not sure if these are still on the market. They have or share the warnings of the class Thiazolidinedione. The second class is Biguanide. This applies to the next two; however, the second class is Sulfonylurea.

The first is Avandaryl, which is a combination of rosiglitazone and glimepiride. The second is Duetact, which is a combination of pioglitazone and glimepiride.

The next mixed is from a Sulfonylurea and Biguanide and is named Glucovance. This is from glyburide and metformin. One type helps your body make more insulin. The other type lowers the amount of glucose made by your liver and helps your insulin work the way it should.

Janumet is a combination of Januvia (sitagliptin), a DPP-4 inhibitor and a Biguanide (metformin). One type helps your body make more insulin when it is needed, especially right after meals. It also helps keep your liver from putting stored glucose into your blood. The other type lowers the amount of glucose made by your liver and helps your insulin work the way it should.

Metaglip is as combination of a Sulfonylurea (glyburide) and a Biguanide (metformin).

The glyburide helps your body make more insulin and metformin lowers the amount of glucose made by the livers and helps your insulin work the way it should.

Kombiglyze is a combination DPP-4 (saxagliptin) and a Biguanide (metformin).

I know there may be other mixed medications, but my sources do not list them and I have not located the press releases for any additional.

Oral Diabetes Medications – Part 2

Part 2 of 3 parts

D-Phenylalanine Derivative There is only one drug in this class, Starlix or nateglinede.

This medication helps your body make more insulin for a short period of time right after meals. The insulin helps keep your blood glucose from going too high after you eat.

The standard for this medication is the same. Do no take this medication if you are pregnant, planning to become pregnant, or breastfeeding. Do not take this medication if you have liver disease.


The potential side effects include low blood glucose or hypoglycemia, weight gain, and dizziness.


DPP-4 Inhibitor: Acronym for Dipeptidyl Peptidase-4 Inhibitor I will cover this class in a separate blog.

Meglitinide This has one drug in its class, Prandin or repaglinide.

This is the medication needed to replace Sulfonylureas if you are allergic to sulfa. This medication is used to make your pancreas produce more insulin for a short period following meals.

You should not take this medication (Prandin) and need to talk to your doctor if you are pregnant, planning to get pregnant, or breastfeeding, or you have liver disease. The side effects of Prandin include low blood glucose (hypoglycemia), weight gain, upset stomach, and back pain or a headache.

Sulfonylurea This is a multi-drug class and can be somewhat confusing as there are two generic only medications plus the generic names apply to several brand names. The medications are Amaryl or glimepiride, DiaBeta or glyburide, Diabinese or chlorpamide, Glucotrol or glipizide, Glucogtrol XL or glipizide long acting, Glynase or glyburide, and Micronase or glyburide. The two generic only are tolazamide and tolbutamide.

These medications work on your pancreas to produce more insulin. When they overwork the pancreas, you will not be able to produce your own insulin.

Who should not take Sulfonylureas - talk with your doctor about whether to take this type of pill if you are allergic to sulfa drugs and you are pregnant, planning to get pregnant, or breastfeeding.

This class has the most numerous medications and causes hypoglycemia by itself or in combination with other medications. These pills are known to cause upset stomach, skin rash, and weight gain.

Thiazolidinedione There are two drugs is this class, Actos or pioglitazine and Avandia or rosiglitazone.


I do not want to discuss this class as one medication has been pulled from the market and the other should be. Actos has been shown to cause bladder cancer and now another study shows it raises diabetic macular edema. Read this link for all the warnings and the Food and Drug Administration advice. This is all I will say on this class.


I will cover the newest class SGLT2 Inhibitor in a separate blog.

Oral Diabetes Medications – Part 1

Part 1 of 3 parts

Either I have the incorrect sources, or I have missed something, but I have only found two acronyms for oral medications. They are:

TZD: Thiazolidinediones. A class of medications that treat
hyperglycemia. Avandia and Actos are the only two medications in this class.

SU: Sulfonylureas. A class of medications that treat hyperglycemia. This class of diabetes medications was the first oral drugs to become available and they help our bodies to release more insulin.

I will cover these plus the remainder of the oral type 2 medications now. I will list the drug class (in bold), then the brand name (always capitalized), and then the generic name (always in small letters).

Biguanide There are three medications in this class. Glucophage or metformin, Glucophage XR (often incorrectly listed as ER) or metformin long acting, and Riomet or metformin liquid.

This medicine, which comes in pill or liquid form, lowers the amount of glucose made by your liver. Then your blood glucose levels don’t go too high. This medicine also helps treat insulin resistance. With insulin resistance, your body doesn’t use insulin the way it should. When your insulin works properly, your blood glucose levels tend to stay on target and your cells get the energy they need. This medication also works to improve your cholesterol levels.

It also may help you lose weight or can be weight neutral. Do not expect this medication to work immediately as this will depend on your body and the dosage prescribed. Because of the immediate side effects, often, your doctor will start you out slowly and gradually increase the dosage. For some, results will happen in one week and for others, the benefits will not become effective for two to three weeks. It is strongly suggested that this medication be taken with food.

You should not take this medication and need to talk to your doctor if you have advanced kidney or liver disease, you drink large amounts of alcoholic beverages, or you are pregnant, planning to get pregnant, or breastfeeding. Sometimes you'll need to stop taking this medication for a short time so you can avoid developing lactic acidosis. If you have severe vomiting, diarrhea, or a fever, or if you can't keep fluids down, call your doctor immediately. You should also talk with your doctor well ahead of time about stopping this type of medicine if you will be having special x rays that require an injection of dye, you will be having surgery, or you will be having a colonoscopy. Your doctor will tell you when it is safe to start taking your medicine again.

This medication will not cause hypoglycemia by itself; however, they will increase your risk if taken with diabetes medications that cause low blood glucose, insulin, or certain other medications. Your doctor should advise you to lower your other diabetes medications while you take this medication.

The side effects are nausea, diarrhea, or an upset stomach when you first start taking this medication. These side effects normally go away or subside after a while. Rarely, a serious condition called lactic acidosis occurs as a side effect of taking this medicine. Call your doctor immediately if you become weak and tired, become dizzy, feel very cold, have trouble breathing, have unusual muscle pain and stomach problems, or have a sudden change in the speed or steadiness of your heartbeat

Alpha-Glucosidase Inhibitor There are two drugs in this class. Glyset or miglitol and Precose or acarbose.

This medication helps keep your blood glucose from going too high after you eat, a common problem in people with diabetes. It works by slowing down the digestion of foods high in carbohydrate, such as rice, potatoes, bread, milk, and fruit. These are foods that you should not be eating or at least limiting in quantity.

You should not take this medication and need to talk to your doctor if you have bowel disease or other intestinal conditions, you have advanced kidney or liver disease, or you are pregnant, planning to get pregnant, or breastfeeding.

The side effects are risky if you do not follow careful guidelines. While it is said that this medication does not cause low blood glucose by itself, risks go up dramatically if combined with medications that cause hypoglycemia or insulin. Here again your doctor should advise you to lower your other diabetes medications while you take this medication. These medications may cause stomach pain, gas, bloating, or diarrhea. These symptoms usually go away after you have taken these pills for a while.

WARNING If you take Glyset or Precose, only glucose tablets or glucose gel will bring your blood glucose level back to normal quickly. Other quick-fix foods and drinks won't raise your blood glucose as quickly because Glyset and Precose slow the digestion of other quick-fix foods and drinks.

Healthy Plate By Joslin, Maybe Not So Healthy

If you are a follower of the ADA food plan, you will enjoy the Joslin healthy plate. If you need to gain some weight, you will love the Joslin healthy plate. Does this tell you what you need to know about the Joslin healthy plate?

It is not as interactive as a person would like and in fact is rather rigid in options, as you would expect a registered dietitian to be because of being a proponent of BIG Food. I attempted to get a variance to help with weight loss, but everything I tried came up the same when I wanted Joslin healthy plate to do the calculations. If I were to follow the plan, I could figure on gaining approximately 5 pounds per month. Some weight loss plan!

Even using a meal plan that you may have and then following this route would not let you have fat or products containing fat. This shows that unless you use their high carbohydrate – low fat (HCLF) foods, you will not even be able to have a balanced meal that you might like to eat. Yes, those with diabetes that are able to consume the HCLF without causing spikes in their blood glucose levels can eat this. For the majority of people with type 2 diabetes, the Joslin healthy plate food plan will not be one that you will find satisfactory.

I can only surmise that the American Association of Diabetes Educators (AADE) and the Academy of Nutrition and Dietetics (AND) has been more influential in reminding their members to follow certain guidelines instead of allowing any deviation from positions not supported by BIG Food.

While the American Diabetes Association (ADA) does now support other food plans including low carbohydrate – high fat (LCHF), the AADE and AND will not allow what the ADA allows. These two groups will continue to loose support among the patient population for their rigid position.