Where Will Invokana (canagliflozin) Fit in Type 2 Diabetes Therapy if Approved

Canagliflozin, brand name Invokana, appears poised to join the already crowded  field of medications for the non-insulin treatment of type 2 diabetes. The FDA advisory committee recommended the approval of this new Jansen Pharmaceuticals drug this week.    Invokana has a unique mechanism of action, preventing the reabsorption of glucose in the kidney and so allowing glucose to be lost in the urine.  If approved this give us a new class of medication for diabetes therapy.  Some of the FDA advisory committee members voiced significant concern about the potential risks of Invokana, an increase in cholesterol levels leading to concern of cardiovascular disease in this diabetic population where the leading cause of death is already cardiac disease, as well as risk of renal injury.  I thought this week’s news of this new drug makes it a good time to review the types of oral medications available now for diabetes therapy, how they work, and theiradvantages, disadvantages and overall role in blood sugar control in type 2 diabetes.  Of course the mainstay of treatment of type 2 diabetes is diet, exercise, weight loss and management of other cardiovascular risk factors including smoking cessation, lipid and blood pressure management.  Here is a tabular summary of the available commonly used non-insulin treatment options for blood sugar control in type 2 diabetes:

Class of Drug Examples Mechanism of Action Pros Cons Summary
Biguanides Metformin Inhibition of gluconeogenesis, the mechanism of glucose production in cells, especially in the liver Inexpensive, usually well tolerated, serious side effects uncommon, weight neutral Contraindicated if renal insufficiency, rare lactic acidosis, fairly common GI side effects First choice drug for type 2 diabetes if no renal insufficiency
Sulfonylureas Glyburide, Glipizide, Glymeperide Stimulate pancreatic insulin release Inexpensive, good formulary coverage Hypoglycemia a major concern, weight gain, benefit tends to wane with sustained use Hypoglycemia risks limit use, and the lack of durability of hypoglycemic response makes it suboptimal.
TZDs (thiazolidinedione) Pioglitazone (Actos) Allow insulin to work better at the cellular level, and to a lesser degree reduce hapatic glucose production Fairly effective, now pioglitazone is generic Weight gain, concern about fluid retention and heart failure (Avandia removed from US market for this reason. Losing favor due to potential for cardiovascular risks
DPP4 inhibitors Januvia, Slow breakdown of GLP-1, which increases post-prandial insulin release No hypoglycemia, weight neutral, sustained efficacy, side effects uncommon Expensive Gaining traction as a second or third medication after metformin
GLP-1 agonist Byetta, Bydureon, Victoza Stimulates the receptor in the pancreas that releases post prandial insulin More potent than some other drugs in reduction of blood sugar, weight loss sometimes noted Injectable, Expensive Gaining favor for patients with primarily post prandial hyperglycemia who need weight loss
Meglitinides Prandin, Starlix Stimulate pancreatic islet cells to release insulin Can help with post prandial hyperglycemia Three times daily drug, hypoglycemia a concern, expensive Seldom used
Alpha-glucosidase inhibitors Precose, Glyset Block breakdown of starches in the intestine Act in the GI tract, few systemic problems GI side effects common, expensive, need to be used at the first bite of each meal Seldom used


So how is the best way to manage blood sugar in type 2 diabetes.  Most important is to understand, emphasize and work hard at behavioral treatment.  A controlled carbohydrate diet, weight loss and exercise are not just the first order of business, but remain critical no matter what medications are chosen.  We do not have drugs that allow diabetes patients to control their blood sugars while eating poorly and not controlling their weight. Metformin remains the mainstay first line drug for most patients.  Exceptions are patients with moderate or worse renal insufficiency or with unacceptable metformin side effects.  The question is what drug to add if metformin is not adequate.  All the other options have significant drawbacks, either cost with the DPP4 inhibitors and GLP-1 agonists  or hypoglycemia with the sulfonylureas. Weight gain and risk of CHF are major considerations with TZDs and the meglitinides and alpha-glucosidase inhibitors have only minor roles.  Insulin is sometime needed.  It’s a balancing act overall, cost, risks, benefits, side effects, and personal choice.  If Invokana  gets FDA approval it will undoubtedly be expensive, and its role will be determined over time.  I suspect it will play a minor role overall.

You may also enjoy earlier posts: How to Treat Diabetes: What’s a Physician to Do? and Traits of a Superstar Diabetic

One Response to Where Will Invokana (canagliflozin) Fit in Type 2 Diabetes Therapy if Approved

  1. I participated in the study for this new drug for 2 years and cannot wait until it comes on the market. I had no side effects. While on the study my fasting readings were less than 100. I just hope I could afford it once it comes on the market or the company can give some kind of discount or assistance for this drug.

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