Diabetes Management DPP-4 Inhibitors
Table 2: Randomised Controlled Clinical Trials with Sitagliptin (Januvia) in Type 2 Diabetes Author
Study Design
Aschner et al., 200659
Charbonnel et al., 200660
Rosenstock et al., 200661
Goldstein et al.,
200762 Nauck et al., 200763
Hermansen et al., 200764
RDBPC RDBPC RDBPC RDBPC RDBAC RDBPC
Duration Number of Dose (weeks)
Patients 24 24 24 24 52 24 741 701 353 340* 1,172 441
100 200 100
100 100 100 100 (mg/day)
Other Antidiabetic Treatment
Diet only Diet only
Diet + metformin Diet + pioglitazone Diet only Diet + metformin Diet + glimepiride Diet + glimepiride + metformin
*Number is the diet + placebo and the diet + sitagliptin arms only. HbA1c = glycated haemoglobin; RDBAC = randomised double-blind active comparator; RDBPC = randomised double-blind placebo controlled.
Table 3: Randomised Controlled Clinical Trials with Vildagliptin (Galvus) in Type 2 Diabetes Author
Study Design
Ahren et al., 200465 Garber et al., 200766
Rosenstock et al., 200767 Schweizer et al., 200768 Bosi et al., 200769
RDBPC RDBPC
RDBAC RDBAC RDBPC
Duration Number of Dose (weeks)
Patients
52 24
24 52 24
107 463
519 780 544
100 50
100 100 100 50
100 (mg/day)
Other Antidiabetic Treatment
Diet + metformin Diet + pioglitazone Diet + pioglitazone Diet only
Diet + metformin Diet + metformin Diet + metformin
*Approximate HbA1c value estimated from illustration. †Decrease in HbA1c was 1.0% diet + vildagliptin versus 1.4% for diet + metformin. HbA1c = glycated haemoglobin; RDBAC = randomised double-blind active comparator; RDBPC = randomised double-blind placebo-controlled.
Table 4: Randomised Controlled Clinical Trials with Saxagliptin (Onglyza) in Type 2 Diabetes Author
Study Design
Rosenstock et al., 200870
DeFronzo et al.,
200971 Chen et al., 200872
200873 Allen et al., 200874
RDBPC RDBPC RDBAC Ravichandran et al., RDBAC RDBPC
Duration Number of Dose (weeks)
Patients 12 24 24 24 24 338 743 1,306 768 565 (mg/day) 2.5, 5,
10, 20, 40 2.5, 5, 10
5, 10 2.5, 5 2.5, 5
Other Antidiabetic Treatment
Diet only Diet + metformin Diet + metformin Diet + glyburide Diet + thiazolidinedione*
* The thiazolidinedione was either pioglitazone or rosiglitazone. HbA1c = glycated haemoglobin; RDBAC = randomised double-blind active comparator; RDBPC = randomised double-blind placebo-controlled.
heart failure should be borne in mind. High dosages of gliptins have been associated with some adverse effects during pregnancy in animals, hence gliptins are not recommended in pregnancy and lactation.57–59
Diverging Actions of the Incretins – Future Prospects
Although there have been reports of pancreatitis among patients taking gliptins, the incidence appears to be similar to that seen in the background population with type 2 diabetes: the occurrence of pancreatitis in type 2 diabetes is about 2.8 times higher than in the non-diabetic population.86
22
It is widely held that the primary physiological role of incretins is to modulate plasma glucose. However, several independent lines of inquiry indicate that incretins have important functions relevant to pathophysiologies other than diabetes. There is a growing body of evidence indicating that incretin-related peptides have cardio- protective and neuroprotective actions that may combat other human
EUROPEAN ENDOCRINOLOGY
Mean
Baseline HbA1c (%)
8.0 8.0
7.96 8.05 8.8 7.5 8.34
Placebo- subtracted
Decrease in HbA1c (%)
↓ 0.79 ↓ 0.94 ↓ 0.65
↓ 0.70 ↓ 0.83 ↓ 0.67
↓ 0.57 ↓ 0.89
Mean
Baseline HbA1c (%)
7.7
8.7* 8.7* 8.7 8.7 8.4
Placebo- subtracted
Decrease in HbA1c (%) ↓ 1.1 ↓ 0.8 ↓ 1.0 ↓ 1.1 ↓ 1.0† ↓ 0.7 ↓ 1.1
Mean
Baseline HbA1c (%)
7.9 8.0 9.5 8.4 8.3
Placebo- subtracted
Decrease in HbA1c (%)
↓ 0.45–0.63 ↓ 0.46–0.56 ↓ 0.50–0.54 ↓ 0.54–0.64 ↓ 0.36–0.64
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