1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...

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compared to a standard breakfast meal test (incremental glucose AUC ~5 fold greater)
(241).
Regarding the mechanisms via which a single dose administration of vildagliptin
(100 mg) before an mixed evening meal improves glucose tolerance and reduces fasting
plasma glucose in DM2, it was shown that increasing insulin secretion rate despite a
significant reduction in plasma glucose (increase in insulinogenic index) and suppressing
plasma glucagon, leads to enhanced suppression of endogenous glucose production.
During the overnight period, endogenous glucose production was significantly reduced and
its decline was positively correlated with the decrease in fasting plasma glucose (242). It
was demonstrated that 12 week treatment of drug-naïve DM2 with vildagliptin (50 mg bid)
compared to placebo, restored the acute insulin response to glucose (AIRg) and the
sensitiviy index (Si) determined during FSIVGTT. The disposition index (DI= AIRg x Si)
increased > 4-fold where part of this effect remained after 2-4 week washout, suggesting
that vildagliptin may exert some disease-modifying effect (243).
Recently, some results from ongoing phase III programmes with vildagliptin have
been presented in the same line described in the Sitagliptin section. One study, comprising
780 patients, compared vildagliptin monotherapy (50mg bid) with metformin. After 52
weeks, HbA1c levels were reduced significantly with both drugs. Vildagliptin was better
tolerated than metformin.Both treatments were weight neutral (244). In a second study
comprising 416 patients, vildagliptin (50 mg qd or bid) or placebo were added to metformin
improving glycemic control when the incretin enhancer was given in comparison to placebo
in a 24-week study. Vildagliptin was well-tolerated and mitigated metformin-induced
gastrointestinal side effects whenever present (245).
A third study comprised 256 patients and compared vildagliptin with placebo in
inadequately controlled DM2 requiring insulin. After 24 weeks, vildagliptin 100mg qd plus
insulin reduced insulin requirements and HbA1c slightly more in comparison with the
patients treated with placebo plus insulin. The hypoglycemic events were less common and
less severe in the vildagliptin-treated patients (246).
Although sitagliptin is not quite as potent as vildagliptin, the available data from
single-dose studies indicate that both compounds have similar clinical efficiency in
reducing glucose excursion after oral glucose administration (247). Data are not yet