John B. Buse, MD, PhD; University of North
Carolina, recently spoke on new drugs in development at the 64th
annual American Diabetes Association's Advanced Postgraduate
Almost 300 companies are involved in developing drugs for type 2
diabetes alone, and additional companies are working on type 1
diabetes and diabetes complications. The list below is itemized
from his speech.
1. Drugs already
released or coming out soon
GLP-1 receptor agonist combined with a basal insulin analog, is
already available; it is a mixture of glargine and lixisenatide.
Soon, liraglutide mixed with insulin degludec will be available as
These drug combinations are exceptionally powerful
glucose-lowering agents in the setting of type 2 diabetes. They are
associated with lower risks for hypoglycemia and less weight gain
than with insulin alone.
"The question is whether we eventually will be using those
agents exclusively instead of basal insulin, or what their place
will be in the therapeutic landscape."
SGLT-2 inhibitors. Ertugliflozin is a new SGLT-2 inhibitor that
is under review by the US Food and Drug Administration. It seems to
work similarly to the agents we have available now.
Sotagliflozin, an SGLT-1/SGLT-2 dual inhibitor, is another agent
that is well advanced into phase 3 trials in patients with type 1
diabetes. This drug has somewhat different properties, and the
early results in the setting of type 1 diabetes are quite
encouraging. That agent could be available within the next couple
GLP-1 receptor agonists. Intarcia Therapeutics has developed
osmotic pump for delivery of exenatide. That pump is about the
size of a matchstick. For 6 or perhaps as long as 12 months, it
will release a steady stream of exenatide into the circulation,
lowering glucose effectively and promoting weight loss, as we
expect from GLP-1 receptor agonists. This may be a huge boon to
patients who are not very good at taking their medications.
Oral GLP-1 agonistsare in development. Semaglutide is a
once-weekly, injected product that is being developed by Novo
Nordisk, but a once-daily oral formulation of semaglutide also
seems to be very active in glucose lowering and weight loss. That
oral formulation is well along in the process of development.
Glucose-responsive insulin (GRI); it used to be called smart
insulin. After this agent is injected, it releases insulin only
when the glucose level is high; it does not release insulin when
the glucose level is low. "This has worked well in mice, and we are
about to begin pig studies." Dr Zhen Gu, an assistant professor in
the Joint Department of Biomedical Engineering at the University of
North Carolina at Chapel Hill and North Carolina State University
in Raleigh has invented a patch for delivery of GRI.
4. New class of
Glucokinase (GK) activatorshave had a checkered past.
Development of previous GK activators was halted because of
problems with hypoglycemia in some cases, hypertriglyceridemia in
some cases, and a loss of efficacy after the first 6 months in
The newer GK activator, being developed by vTv Therapeutics in
High Point, North Carolina, seems to have overcome those barriers.
They are designing studies with their GK activator in patients with
type 1 diabetes. These studies will begin enrollment in the near
future. They also hope to develop this drug for use in type 2
Dr. Buse's practice combines
clinical care, research and education. He has received
international recognition for innovative clinical care and efforts
at prevention of type 1 diabetes, type 2 diabetes and their
complications. He practices patient-centered care focusing on
developing treatment programs in collaboration with patients that
meet their needs and expectations. He works with teams of
investigators in diabetes clinical trials, comparative
effectiveness research and translation of basic science research
towards clinical application. Current projects focus in novel
treatments including development of glucose-responsive insulin,
cardiovascular safety and efficacy of diabetes drugs and developing
the evidence-base for treatment guidelines of the future in