Medicine has been awash over the past decade or so in new types of drugs to treat type 2 diabetes, but the impact of this abundance on improving patient care remains uncertain. Perhaps because of this, or despite it, the number of new antihyperglycemic drugs continues to grow.
At the annual meeting of the European Association for the Study of Diabetes (EASD) in Berlin in early October, during different sessions and with no signs of coordination, two speakers put the same image up on the screen during their talks. Both images graphically depicted and contrasted the pace of drug introductions for diabetes and for hypertension over the past 60 years or so.
Jina Lee/Wikimedia Commons
For antihypertensives, the pace was steady and linear: Ten drug classes came out during the years from 1950 to now at a steady clip of one or two each decade.
In contrast, drugs aimed at reducing blood sugar or boosting insulin release or sensitivity languished for a long time, with only two drug classes available until the 1990s, insulin and the sulfonylureas. But starting with the introduction of metformin, the first Food and Drug Administration–approved biguanide, at the end of 1994, the FDA approved drugs from eight additional drug classes, a rate of a new drug type every 2 years.
Why such a striking difference, especially during the past 10 years when commercial interest in new drug development for blood pressure–lowering drugs has dwindled to virtual indifference? I asked one of the speakers who made the comparison during the meeting, Yale diabetologist Silvio Inzucchi.
"The drugs now available to treat hypertension are reasonably good, so why waste money developing new agents when most patients are successfully treated with what we have?" he queried. However, "in diabetes we still have significant side effects, and no diabetes drug – except perhaps insulin – is universally effective. So there remains room for better, more effective, and safer medications. I am still waiting for the perfect diabetes drug."
It might come as news to physicians who treat hypertension that they have "perfect" drugs to prescribe, but the antihypertensive big three of diuretics, beta-blockers, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers have pretty much become the mainstays of blood pressure reduction. For diabetes, the situation is not nearly so clear.
Last June, the EASD and the American Diabetes Association released recommendations on managing type 2 diabetes (a panel cochaired by Dr. Inzucchi). The groups named metformin as their initial go-to drug, and highlighted five other drug classes as the top choices for a second or third drug to add for patients who need more than metformin. Those five other drug classes are sulfonylureas (like glipizide), thiazolidinediones (like pioglitazone), DPP-4 inhibitors (like sitagliptin), GLP-1 receptor agonists (like exenatide), and insulin.
That means the top tier of recommended drugs includes only three of the agents that have come on the scene in the recent rush of the past 17 years – the thiazolidinediones, the DPP-4 inhibitors, and the GLP-1 receptor agonists. The recommendation panel decided that five other recently-approved drug classes did not really add much to the treatment mix.
As Dr. Inzucchi told me:
"The drugs we left off the main figure are suboptimal for a variety of reasons. Some are minimally effective, some very expensive, some have intolerable side effects, and some are too hard to take.
"There is still room for more agents, but they have to be safer, better tolerated, and preferably more durable in their effectiveness than what we currently have," he said.
Other reports at the EASD meeting showed that the wave of new drug types for treating diabetes will not ebb soon. Agents awaiting regulatory action or in clinical studies include SGLT2 inhibitors, dual PPAR-receptor agonists, SIRT1 activators, and glucagon-receptor antagonists.
The number of alternatives for treating diabetes is no longer the issue. The question is, how many of the different drug types really help patients?
–Mitchel Zoler (on Twitter @mitchelzoler)