Table 2.
PPG outcomes as add-on to metformin: selected trials published from 2008 to October 2012
| Drug | Baseline demographics
|
Treatments | PPG outcome | ||
|---|---|---|---|---|---|
| Patients, n | Male/female, n/n | Mean age (SD), years | |||
| GLP-1 analogs | |||||
| Exenatide60 | 234 | 48%/52% | 55 (9) | • Exenatide 5 μg bid for 4 weeks and 10 μg bid for 12 weeks • Matching placebo |
Mean decrease in morning, midday, and evening PPGE at week 16 significant for exenatide plus metformin versus placebo plus metformin (P<0.001) |
| Exenatide61,62 | • Exenatide, 205 • Insulin glargine, 209 |
• 55%/45% • 55%/45% |
• 59 (9) • 57 (10) |
• Exenatide 5 μg bid for 4 weeks and then 10 μg bid, with titration up to 20 μg tid if needed • Insulin glargine 10 U qd followed by self-adjusted dosing |
Mean decrease in PPG AUC at weeks 26 and 52 significant for exenatide plus metformin versus insulin glargine plus metformin (P<0.001) |
| Exenatide63 | 30 | 11/19 | 53 (11) | • Exenatide 5 μg bid for 1 week and 10 μg bid for 1 week • Matching placebo |
Mean morning, midday, and evening 2-hour PPG at week 2 significantly lower for exentatide plus metformin versus placebo plus metformin (P≤0.001) |
| Lixisenatide79 | • 5 μg qd, 55 • 10 μg qd, 52 • 20 μg qd, 55 • 30 μg qd, 54 • 5 μg bid, 53 • 10 μg bid, 56 • 20 μg bid, 54 • 30 μg bid, 54 |
• 26/29 • 31/21 • 28/27 • 27/27 • 25/28 • 29/27 • 20/34 • 23/31 |
• 57 (8) • 55 (9) • 55 (10) • 57 (9) • 57 (8) • 56 (8) • 57 (8) • 55 (9) |
• Lixisenatide 5, 10, 20, or 30 μg qd or bid • Matching placebo |
Mean decreases in morning 2-hour PPG at week 13 significant for all doses of lixisenatide plus metformin versus placebo plus metformin (P<0.01 except for lowest dose given qd or bid [P<0.05]) |
| DPP-4 inhibitors | |||||
| Sitagliptin146 | • Sitagliptin, 248 • Glipizide, 256 |
• 142/106 • 161/95 |
• 58 (9) • 57 (9) |
• Sitagliptin 100 mg qd • Glipizide 5 mg qd |
Mean decrease from baseline to year 2 in PPG AUC seen with sitagliptin plus metformin but not glipizide plus metformin |
| Saxagliptin147 | 93 | 49/44 | 55 (9) | • Saxagliptin 5 mg qd • Matching placebo |
Mean decreases from baseline to week 4 in 2-hour and 4-hour PPG (evening meal) significant with saxagliptin plus metformin versus placebo plus metformin (P≤0.0010) |
| Saxagliptin113 | • 2.5 mg, 192 • 5 mg, 191 • 10 mg, 181 |
• 83/109 • 103/88 • 95/86 |
• 55 (10) • 55 (10) • 54 (10) |
• Saxagliptin 2.5, 5, or 10 mg qd • Matching placebo |
Mean decreases from baseline to week 24 in 2-hour PPG and PPG AUC significant with all doses of saxagliptin plus metformin versus placebo plus metformin (P≤0.0001) |
| Saxagliptin148 | • Saxagliptin + metformin, 138 • Metformin, 144 |
• 57/81 • 73/71 |
• 55 (9) • 56 (10) |
• Saxagliptin 5 mg + metformin XR 1500 mg qd • Metformin XR 2000 mg qd |
Mean decreases from baseline to week 18 in 2-hour PPG significant with saxagliptin plus metformin XR 1,500 mg versus metformin XR 2,000 mg (P=0.0013) |
| Vildagliptin122,149 | 2,789 | 1,490/1,299 | 57 (9) | • Vildagliptin 50 mg bid • Glimepiride 6 mg qd |
Mean decrease from baseline to year 2 in PPG AUC similar with vildagliptin plus metformin and glimepiride plus metformin |
| Linagliptin112 | 700 | 379/321 | 57 (10) | • Linagliptin 5 mg qd • Matching placebo |
Mean decrease from baseline to week 24 in 2-hour PPG levels significant with linagliptin plus metformin versus placebo plus metformin (P<0.0001) |
Abbreviations: AUC, area under the curve; bid, twice daily; DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1; PPG[E], postprandial glucose [excursion]; qd, once daily; SD, standard deviation; tid, three times daily; XR, extended release.