Dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes: safety, tolerability, and efficacy

Figures & data

Table 1 Dipeptidyl peptidase inhibitors efficacy trials summary

Study author	Number patients	Dose	Compared to	Add-on to	Trial duration	Baseline mean hemoglobin A1c	Mean hemoglobin A1c reduction^a
Sitagliptin
Raz^Citation16	521	100 or 200 mg daily	Placebo	Diet/exercise	18 weeks	8.1%	100 mg: 0.6% 200 mg: 0.48%
Aschner^Citation70	741	100 or 200 mg daily	Placebo	Diet/exercise	24 weeks	8.0%	100 mg: 0.79% 200 mg: 0.94%
Scott^Citation82	743	5, 12.5, 25, 50 mg twice daily	Placebo	Diet/exercise	12 weeks	7.9%	Range: 0.38%–0.77% (dose-dependent response) 50 mg bid: 0.77%
Hanefield^Citation81	555	25, 50, 100 mg daily, 50 mg twice daily	Placebo	Diet/exercise	12 weeks	7.6%–7.8%	Range: 0.39%–0.56% 100 mg daily: 0.56%
Raz^Citation52	190	100 mg daily	Placebo	Metformin	30 weeks	9.2%	0.94%
Charbonnel^Citation53	701	100 mg daily	Placebo	Metformin	24 weeks	8%	0.65%
Scott^Citation54	273	100 mg daily	Placebo	Metformin	18 weeks	7.7%	0.51%
Hermansen^Citation55	441	100 mg daily	Placebo	Glimeperide or glimepride + metformin	24 weeks	8.3%	0.74% (overall) Glimeperide only: 0.89% Glimeperide + metformin: 0.57%
Rosenstock^Citation32	353	100 mg daily	Placebo	Pioglitazone	24 weeks	8.0%	0.70%
Goldstein^Citation56	1091	100 mg daily	Placebo or metformin or sitagliptin/metformin combination	Diet/exercise	24 weeks	8.8%	M2000/S100: 2.07% M1000/S100: 1.57% M2000: 1.30% M1000: 0.99% S100: 0.83%
Nauck^Citation57	1172	100 mg daily	Glipizide 5 to 20 mg daily	Metformin	52 weeks	7.5%	0.67% from baseline – noninferior to glipizide
DeFronzo^Citation58	61	100 mg daily	Exenatide 10 μg twice daily	Metformin	2 weeks, with 2-week cross-over	8.5%	Post-prandial glucose measured as outcome: Exen: 133 mg/dL Sita: 208 mg/dL (difference followed drug after cross-over)
Scott^Citation54	273	100 mg daily	Rosiglitazone 8 mg	Metformin	18 weeks	7.7%	0.51% – noninferior to rosiglitazone
Vildagliptin
Pratley^Citation71	98	25 mg twice daily	Placebo	Diet/exercise	12 weeks	8.0%	0.6%
Pi-Sunyer^Citation107	354	50 mg daily, 50 mg twice daily, 100 mg daily	Placebo	Diet/exercise	24 weeks	8.4%	50 mg daily: 0.5% 50 mg twice daily: 0.7% 100 mg daily: 0.9%
Dejager^Citation108	632	50 mg daily, 50 mg twice daily, 100 mg daily	Placebo	Diet/exercise	24 weeks	8.5%	50 mg daily: 0.8% 50 mg twice daily: 0.7% 100 mg daily: 0.9%
Scherbaum^Citation109	306	50 mg daily	Placebo	Diet/exercise	52 weeks	6.7%	0.3%
Scherbaum^Citation83	131	50 mg daily	Placebo	Diet/exercise	104 weeks (52 weeks then 4-week wash-out, then 52 weeks)	6.6%	1 year: 0.3% 2 years: 0.5%
Ristic^Citation84	279	25, 50, 100 mg daily, 25 mg twice daily	Placebo	Diet/exercise	12 weeks	7.7%	50 mg daily: 0.56% 100 mg daily: 0.53% Other groups were not statistically significantly different from placebo
Schweizer^Citation68	780	100 mg daily	Metformin	Diet/exercise	52 weeks	8.7%	Vildagliptin: 1.0% Metformin: 1.4% Vildagliptin effect did not reach statistical noninferiority
Goke^Citation69	463	100 mg daily	Metformin	Diet/exercise	104 weeks (52 week extension of previous study^Citation68)	Vildagliptin: 8.4% Metformin: 8.8%	Vildagliptin: 1.0% Metformin: 1.5% Vildagliptin effect did not reach statistical noninferiority
Rosenstock^Citation64	786	50 mg twice daily	Rosiglitazone	Diet/exercise	24 weeks	8.7%	1.1% – noninferior to rosiglitazone
Rosenstock^Citation65	607	100 mg daily	Pioglitazone 30 mg vs vildagliptin + pioglitazone combination (100/30 mg daily or 50/15 mg daily)	Diet/exercise	24 weeks	8.7%	Vildagliptin: 1.1% Pioglitazone: 1.4% 100/30 mg daily: 1.9% 50/15 mg daily: 1.7%
Pan^Citation67	661	50 mg twice daily	Acarbose	Diet/exercise	24 weeks	8.6%	Vildagliptin: 1.4% Acarbose: 1.3%
Bosi^Citation59	484	50 or 100 mg daily	Placebo	Metformin	24 weeks	8.4%	50 mg daily: 0.7% 100 mg daily: 1.1%
Ahren^Citation60	57	50 mg daily	Placebo	Metformin	52 weeks	7.7%	1.0%
Garber^Citation61	515	50 mg daily or twice daily	Placebo	Glimeperide 4 mg daily	24 weeks	8.5%	50 mg daily: 0.6% 50 mg twice daily: 0.7%
Garber^Citation62	463	50 or 100 mg daily	Placebo	Pioglitazone	24 weeks	8.7%	50 mg daily: 0.8% 100 mg daily: 1.0%
Fonseca^Citation63	296	50 mg twice daily	Placebo	Insulin	24 weeks	8.4%	0.3%
Bolli^Citation66	576	50 mg twice daily	Pioglitazone	Metformin	24 weeks	8.4%	0.9% from baseline – noninferior to pioglitazone
Saxagliptin
Rosenstock^Citation72	338	2.5, 5, 10, 20 or 40 mg daily	Placebo	Diet/exercise	12 weeks	7.9%	0.45%–0.63%
Rosenstock^Citation72	85	100 mg daily	Placebo	Diet/exercise	6 weeks	7.8%	0.73%
Rosenstock^Citation47	401	2.5, 5, or 10 mg daily	Placebo	Diet/exercise	24 weeks	Main treatment cohort: 7.9% Open-label cohort: 10.7%	Main treatment cohort 2.5 mg daily: 0.62% 5 mg daily: 0.65% 10 mg daily: 0.73% Open label cohort: 1.87%
DeFronzo^Citation73	743	2.5, 5, or 10 mg daily	Placebo	Metformin	24 weeks	8.0%	2.5 mg daily: 0.73% 5 mg daily: 0.83% 10 mg daily: 0.72%
Jadzinsky^Citation75	1306	10 mg daily	Metformin or metformin + saxagliptin 5 mg or 10 mg daily	Diet/exercise	24 weeks	9.4%–9.6%	Saxabliptin: 1.7% Metformin: 2.0% Combination (both): 2.5% (Combinations statistically superior to either monotherapy)
Chacra^Citation74	768	2.5 or 5 mg daily	Glyburide uptitrated to 15 mg daily	Glyburide 10 mg maximum	24 weeks	8.4%–8.5%	2.5 mg daily: 0.54% 5 mg daily: 0.64% Glyburide uptitration: +0.08%
Alogliptin
Nauck^Citation76	527	12.5 or 25 mg daily	Placebo	Metformin	26 weeks	7.9%–8.0%	12.5 mg daily: 0.5% 25 mg daily; 0.5%
Pratley^Citation77	500	12.5 or 25 mg daily	Placebo	Glyburide	26 weeks	8.1%	12.5 mg daily: 0.39% 25 mg daily: 0.53%
Rosenstock^Citation78	390	12.5 or 25 mg daily	Placebo	Insulin with or without metformin	26 weeks	9.3%	12.5 mg daily: 0.50% 25 mg daily: 0.58%

a Placebo-subtracted, statistically significant hemoglobin A_1c value unless stated otherwise.

Abbreviations: M2000/S100, metformin 2000 mg, sitagliptin 100 mg; M1000/S100, metformin 1000 mg, sitagliptin 100 mg; M2000, metformin 2000 mg; M1000, metformin 1000 mg; S100, sitagliptin 100 mg.

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