Vildagliptin may be a better treatment
option than repaglinide for Type 2 diabetes in patients who also
have symptomatic coronary artery disease (CAD), research
suggests.

Presenting her findings at a poster session at the American
Diabetes 70th Scientific Sessions in Orlando, Florida, USA, Rosa
Rahmi, from the University of Sao Paulo in Brazil, explained that
her team had found repaglinide was more likely to eliminate
ischemic preconditioning (IPC), which protects against myocardial
necrosis, in these patients than vildagliptin.

IPC refers to the “phenomenon in which short periods of
myocardial ischemia promote resistance to a subsequent ischemic
insult,” she said.

The cellular pathways underlying this phenomenon appear to
involve the ATP-potassium channel.

Rahmi and team sought to investigate the effect of two
hypoglycemic agents - vildagliptin and repaglinide - on IPC in 83
patients with Type 2 diabetes and a positive exercise test, who
also had multivessel coronary disease confirmed by coronary
angiography.

Of these patients, 42 were receiving repaglinide 2 mg and 41
were receiving vildagliptin 100 mg.

Five days before the study started, nitrates, calcium entry
blocking agents, beta blockers, angiotensin-converting enzyme
inhibitors, angiotensin II receptor blockers, and sulfonylurea
drugs were withdrawn.

The participants completed phase I, which involved two
sequential exercise treadmill tests (T1 and T2), with a 30-minute
gap, while not taking hypoglycemic agents. They then took the
hypoglycemic agents for a week and completed phase II involving
another two sequential exercise treadmill tests (T3 and T4).

All the patients experienced ischemia (1.0-mm ST-segment
depression) during each of the exercise tests. IPC was demonstrated
by an increase in the time to the onset of ischemia between T1 and
T2.

In phase II, however, 83% of patients taking repaglinide
experienced ischemia significantly earlier in T4 than in T3 (298
seconds vs 337 seconds, respectively), indicating the cessation of
IPC. In comparison, cessation of IPC occurred in just 28% of
patients taking vildagliptin, while 72% preserved the protective
effect.

The researchers propose that IPC might be diminished by
repaglinide because it exerts its effects by binding to the
sulfonylurea receptor, which regulates ATP-potassium channel
activity.

Vildagliptin, on the other hand, is a dipeptidyl peptidase-4
inhibitor and so exerts its glucose-lowering effects through the
interaction of glucagon-like peptide 1 with a specific receptor
located on the cell membrane of the pancreatic beta cells.

The researchers concluded that because vildagliptin did not
affect IPC in a “relevant way” in patients with Type 2 diabetes and
CAD, it may be a “good alternative treatment in this
population.”

They call for further studies to determine the mechanisms
underlying this protection.

MedWire (www.medwire-news.md) is an independent clinical news
service provided by Current Medicine Group, a trading division of
Springer Healthcare Limited. © Springer Healthcare Ltd;
2010

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