Diabetes Management
Table 1: Clinical Trial Efficacy Data for Marketed Dipeptidyl Peptidase-4 Inhibitors in the Treatment of Type 2 Diabetes Treatment Indication, Administration Effect of Treatment from Baseline versus Placebo on:
Reference HbA1c Sitagliptin Sitagliptin Sitagliptin Sitagliptin
Sitagliptin versus placebo plus -0.7 % versus -0.54 % pioglitazone for 24 weeks
(p<0.001)
100 or 200 mg monotherapy -0.48 % and -0.36 % versus versus placebo for 18 weeks 0.12 % (both p<0.001)
100 mg or placebo plus metformin for 24 weeks Sitagliptin 100 mg qd Metformin 500 mg bid Metformin 1,000 mg bid Sitagliptin 50 mg +
metformin 500 mg bid Sitagliptin 50 mg + metformin 1,000 mg bid versus placebo
Saxagliptin 2.5 mg, 5 mg, or 10 mg plus metformin
versus metformin alone for 24 weeks
Saxagliptin 5 mg or 10 mg plus
metformin or saxagliptin 10 mg alone versus
metformin alone for 24 weeks
Saxagliptin 2.5 mg or 5 mg in combination -0.54 % and -0.64 % versus with glyburide 7.5 mg versus glyburide 10 mg alone for 24 weeks
+0.08 % (both p<0.0001) Saxagliptin 2.5 mg or 5 mg plus thiazolidinedione versus
placebo plus thiazolidinedione for 24 weeks
Linagliptin 2.5 mg, 5 mg, 10 mg, or placebo for 28 days
-0.31 %, -0.37 %, and
-0.28 % placebo-corrected mean change (p<0.025)
-0.66 % and -0.94 % versus -0.30 % (both p<0.001)
-7.0 mg/dl and -10.0 mg/dl
-0.59 %, -0.69 %, and -0.58 % -14.31 mg/dl, -22.03 mg/dl, versus +0.13 % (all p<0.0001) and -20.50 mg/dl versus +1.24 mg/dl (all p<0.0001)
-2.5 % and -2.5 % versus -1.7 % -60 mg/dl and -62 mg/dl (all p<0.001)
Mean changes from baseline at Week 24: -1.43 kg, -0.87 kg, and -0.53 kg versus -0.92 kg for metformin alone
and -1.1 kg for the saxagliptin DeFronzo, 200983
-0.67 % versus -0.02 % (p<0.001)
-0.66 %, -0.82 %, -1.13 %, -1.40 %, and -1.90 %
FPG
-12.6 mg/dl (p<0.001) and -10.8 mg/dl (p<0.01) versus 7.2 mg/dl
-17.5 mg/dl, -27.3 mg/dl, Body Weight
-17.7 mg/dl versus -11.0 mg/dl +1.8 kg versus +1.5 kg (p<0.001)
-0.6 kg and -0.2 kg versus -0.7 kg
-16.2 mg/dl versus 9.0 mg/dl Small decreases were (p<0.001)
observed (0.6–0.7 kg) Significant weight loss in all -29.3 mg/dl, -47.1 mg/dl, and groups (p<0.05) except
versus +0.17 % (all p<0.001) -63.9 mg/dl versus +5.8 mg/dl sitagliptin group, which (all p<0.001)
showed no change
Rosenstock et al., 200629
Raz et al., 200619
Charbonnel et al., 200624
Goldstein et al. 200721
Mean changes from baseline Jadzinsky et al.
and -2.0 % (all p<0.0001 versus versus -31 mg/dl and -47 mg/dl at Week 24: -1.8 kg, -1.4 kg, 200937 monotherapy)
groups versus -1.6 kg for metformin alone
+0.7 kg and +0.8 kg with
versus +1.0 mg/dl (p=0.0218 saxagliptin versus +0.3 kg and p=0.002)
with up-titrated glyburide (both p<0.05)
-14.4 mg/dl (p=0.0053) and +1.3 kg and +1.4 kg
-18.0 mg/dl (p=0.0005) versus versus +0.9 kg -3.6 mg/dl
-19.2 mg/dl, -21.4 mg/dl, and -0.9 kg to -1.6 kg for 16.6 mg/dl versus 3.2 mg/dl treatment groups versus (p<0.025)
-1.8 kg for placebo Bid = twice daily; DPP-4 = dipeptidyl peptidase-4; FPG = fasting plasma glucose; HbA1c = glycosylated hemoglobin; qd = once daily.
Hollander et al., 200942
Chacra et al., 200941
Forst et al., 201184
protocol population (n=504).26
A 30-week RCT in 1,035 patients with type 2
diabetes showed that sitagliptin was non-inferior to glimepiride, and an 18-week study in 273 patients found no difference between sitagliptin and rosiglitazone (both in combination with metformin) with regard to HbA1c.27,28
Studies have demonstrated the efficacy of sitagliptin in combination with thiazolidinediones.29,30
treatment reduced HbA1c levels by 0.70 % from baseline compared with placebo (between-treatment difference in least squares mean, p<0.001)
and FPG by 17.64 mg/dl (p<0.001) in a 24-week RCT in 353 patients with established type 2 diabetes (mean diabetes duration 6.1 years).29 Sitagliptin/metformin combination also achieved better glycemic control than metformin alone as first-line drug treatment in 520 patients.30
HbA1c
levels were reduced from baseline by 2.4 % and 1.5 % with the combination therapy and the monotherapy, respectively (treatment difference -0.9 %, p<0.001).30
FPG and two-hour post-prandial plasma
glucose (PPG) also fell significantly more with the sitagliptin/metformin combination than with metformin alone (-63.0 mg/dl versus -39.6 mg/dl
84 Adding sitagliptin to ongoing pioglitazone
Evidence also supports the efficacy of sitagliptin as an adjunct to insulin in patients with long-standing type 2 diabetes (mean disease duration 12–13 years). Adding sitagliptin to ongoing insulin treatment in 641 patients with
type 2 diabetes significantly reduced HbA1c compared with placebo (-0.6 % versus 0.0 %, p<0.001) over 24 weeks. FPG and two-hour PPG also fell significantly in sitagliptin-treated patients, with placebo-adjusted mean changes of -14.4 mg/dl and -36.0 mg/dl, respectively (p<0.001).32
Saxagliptin
Studies have demonstrated the clear benefits of saxagliptin as monotherapy and in combination with metformin, a sulfonylurea, or a thiazolidinedione.33–40
US ENDOCRINOLOGY
and -113.4 mg/dl versus -68.4 mg/dl, respectively; both p<0.001). When added to glimepiride alone or glimepiride plus metformin, sitagliptin is linked with improved glycemic control: after 24 weeks, compared with
placebo, there was a 0.74 % HbA1c reduction with sitagliptin added to glimepiride alone (p<0.001) and a 0.89 % HbA1c reduction with sitagliptin added to glimepiride plus metformin.31
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