Effectiveness of sitagliptin compared to sulfonylureas for type 2 diabetes mellitus inadequately controlled on metformin: a systematic review and meta-analysis

Abstract

Objective: To assess the effectiveness of sitagliptin compared to sulfonylureas as add-on to metformin in adults with type 2 diabetes mellitus from both randomised controlled trials (RCTs) and 'real-world' non-randomised studies.

Methods and analyses: We conducted a systematic review of EMBASE, MEDLINE, CENTRAL and grey literature for RCTs and non-randomised studies. We reported outcomes relating to change in HbA1c, fasting glucose, weight, blood pressure and lipids from baseline and need for treatment change. No study investigating macrovascular and microvascular diabetes complications was found. Meta-analysis was used where studies were sufficiently homogenous.

Results: Seven RCTs and five non-randomised studies were eligible for inclusion from 1335 articles retrieved. Meta-analysis of three homogenous RCTs revealed a statistically significant decrease in weight with sitagliptin when compared to sulfonylureas (weighted mean difference (WMD) -2.05 kg; 95% CI -2.38 to -1.71); however, a similar change from baseline in HbA1c (WMD 0.05; 95% CI -0.03 to 0.12), fasting glucose (WMD 0.11; 95% CI -0.08 to -0.29), blood pressure, lipids and the proportion achieving HbA1c <7% by study end (OR 0.98; 95% CI 0.85 to 1.13) was observed.Non-randomised studies identified consisted of four prospective and one retrospective cohort study. Three of these five studies were of moderate/high quality, and results though less precise suggested similar real-world comparative glycaemic and weight effectiveness for both treatments. Data from two cohort studies suggested that treatment change (HR 0.65; 95% CI 0.57 to 0.73) and insulin initiation (HR 0.76; 95% CI 0.65 to 0.90) were less likely among those prescribed sitagliptin; however, inadequate reporting of HbA1c at time of treatment change made interpreting results challenging.

Conclusion: Sitagliptin users experienced modest weight loss compared to gain with sulfonylureas; however, this difference was around 2 kg, which may not be of major clinical significance for most individuals. Similar change was observed across most other effectiveness outcomes reported. Further studies are needed to address longer-term effectiveness outcomes for sitagliptin compared to sulfonylureas as add-on to metformin.

Prospero registration number: CRD42016033983.

Keywords: meta-analysis; metformin; sitagliptin; sulfonylurea; systematic review; type 2 diabetes.

Figure 1

PRISMA flow diagram: study identification, selection and exclusions. *Monthly automated alerts from 01/11/15 to 01/06/16 consisting of updates to the search strategy identified additional articles in Embase, Medline and CENTRAL that have been included in the flow diagram above. However, no eligible studies for inclusion were obtained through these updates

Figure 2

Forest plots comparing sitagliptin and sulfonylureas for change from baseline in hbA1c (%) (A), weight (kg) (B), fasting plasma glucose (mmol/mol) (C) and for proportions achieving a hbA1c <7% (53 mmol/mol) at end of study (D). Dur, duration in months; Mean Diff, mean difference; NA, not applicable; Obs, Non-randomized Observational study; OR, Odds ratio; Rct, Randomized controlled trial; SD, Standard deviation; Sita, sitagliptin; Sulf, sulfonylureas;  Tot, total participants.  Note: Weights where present are from Fixed effects meta-analysis though Random-effects estimates were identical. Tau²=0% for all meta-analyses

Figure 3

Forest plots comparing sitagliptin and sulfonylureas for change from baseline for systolic blood pressure (mm Hg) (A), diastolic blood pressure (mm Hg) (B), triglycerides (mmol/l) (C), total cholesterol (mmol/mol) (D), risk of needing treatment change (E) and risk of initiating insulin (F). Dur, duration in months; HR, hazard ratio; Mean Diff, mean difference; Obs, non-randomised observational study; Rct, randomised controlled trial; SD, standard deviation; Sita, sitagliptin; Sulf, sulfonylureas.