Table 2.

Main pharmacological differences between currently available dipeptidyl‐peptidase‐4 inhibitors

Characteristic	Sitagliptin69, 82	Vildagliptin70	Saxagliptin71, 81	Alogliptin72, 80	Linagliptin7, 28
Therapeutic dose (mg)	100	50	5	25	5
Relative (fold) in vitro selectivity for DPP‐4 vs DPP‐8 or DPP‐9	>2,60073	<30074	<45075	>10,00076	>10,00022
Fraction bound to plasma protein	Intermediate	Low	Low	Low	High
Renal excretion route	Major	Intermediate	Major	Major	Minor
Need for dose adjustment for renal impairment	Yes (moderate or severe)	May be required (limited experience)	Yes (moderate or severe)	Yes (moderate or severe)	No
Need for dose reduction with hepatic impairment (mild/moderate)	No (No experience in patients with severe hepatic impairment)	Not recommended for patients with hepatic impairment	No (Not recommended for patients with severe hepatic impairment)	No (No experience in patients with severe hepatic impairment)	No
Drug interaction potential	Low	Low	Intermediate	Low	Low
Efficacy – HbA1c lowering	Similar efficacy	Similar efficacy	Similar efficacy	Similar efficacy	Similar efficacy
Overall safety†	Good Most frequent AEs‡: URTI, nasopharyngitis, headache Risk of hospitalization for HF, HR: 1.00 (95% CI, 0.83 to 1.20) vs placebo77 Postmarketing reports of acute pancreatitis, acute renal failure, hypersensitivity reactions, exfoliative skin conditions; also reports of arthralgia	Good Common AEs§: dizziness Risk of HF unknown Postmarketing reports of hepatitis, urticaria, pancreatitis, skin lesions; also reports of arthralgia	Good Most frequent AEs‡: URTI, UTI, headache Risk of hospitalization for HF, HR: 1.27 (95% CI, 1.07 to 1.51) vs placebo78 Postmarketing reports of pancreatitis, hypersensitivity reactions, and severe arthralgia	Good Most frequent AEs‡: Nasopharyngitis, headache, URTI, abdominal pain, gastroesphageal reflux, rash Risk of hospitalization for HF, HR: 1.07 (95% CI, 0.79 to 1.46)79 Postmarketing reports of acute pancreatitis, hypersensitivity reactions, and hepaticfailure; also reports of arthralgia	Good Most frequent AEs‡: Nasopharyngitis, cough, rash, raised blood enzyme amylase, diarrhea Risk of HF unknown; data from pooled analysis show hospitalization for HF, HR: 1.04 (95% CI, 0.43 to 2.47)83 Postmarketing reports of acute pancreatitis and hypersensitivity reactions, exfoliative skin conditions; also reports of arthralgia

^†For all dipeptidyl‐peptidase‐4 (DPP‐4) inhibitors listed, hypoglycemia is reported more frequently with concomitant sulfonylurea (SU) or insulin therapy. ^‡Most frequent adverse event (AEs) are those listed in prescribing information to occur in ≥5% of patients and more frequently than with placebo. ^§Common AEs defined as a frequency of ≥1/100 to <1/10. CI, confidence interval; HbA1c, glycated hemoglobin; HF, heart failure; HR, hazard ratio; URTI, upper respiratory tract infection; UTI, urinary tract infection.