Eighteen studies (8,327 participants, range 38 to 1,172) were included in the review. Overall risk of bias was unclear for most studies; three studies were considered to have a high risk of bias. All studies were double blind but in some cases it was not clear who was blinded. In no cases was incomplete outcome data addressed.
Sitagliptin versus placebo: Sitagliptin was significantly associated with a reduction in HbA1c (WMD 0.74, 95% CI 0.63 to 0.85; Ι²=45%; 11 studies), fasting plasma glucose (WMD 1.20, 95% CI 1.03 to 1.38; Ι²=31%; 11 studies) and HOMA-β (WMD -10.94, 95% CI -14.07 to -7.8; Ι²=0%; 12 studies) compared to placebo. Similar results were found in studies in which patients used other oral hypoglycaemics and those in which they did not.
Sitagliptin versus active control: Other oral hypoglycaemic monotherapy was significantly associated with a greater reduction in HbA1c than sitagliptin monotherapy (WMD -0.14, 95% CI -0.24 to -0.04; Ι²=7%; three studies) and fasting plasma glucose (WMD -0.73, 95% CI -1.32 to -0.13; Ι²=78%; three studies). Using sitagliptin as an add-on therapy was as efficacious as other oral hypoglycaemics. Sitagliptin as either monotherapy or an add-on therapy was not effective in altering HOMA-β.
Safety outcomes: There was no difference in incidence of hypoglycaemia or serious adverse events in sitagliptin compared to active control groups or in the incidence of serious adverse events in sitagliptin compared to placebo. Sitagliptin as an add-on therapy was associated with a higher risk of hypoglycaemia than placebo as an add-on therapy (RR 2.21, 95% CI 1.53 to 3.18; Ι²=55%; six studies).