Randomized controlled trials (RCTs) have evaluated the efficacy of dipeptidyl peptidase-4 inhibitors (DPP-4i) as add-on therapy to insulin compared to insulin alone in T2DM patients, while there have been differences in the magnitude of the outcome effect across studies. This updated systematic review and meta-analysis aimed to evaluate the effect of DPP-4i in combination with insulin on HbA1c in T2DM patients.

MEDLINE, EMBASE, and Cochrane databases were searched for RCTs that compared DPP-4i plus insulin to insulin alone for T2DM patients, with or without background therapy with other oral agents. The primary endpoint was the absolute change of HbA1c from baseline. Weighted mean difference (WMD) with 95% confidence intervals (CI) was calculated using a random effect model. The methodological quality of included RCTs was evaluated using the Cochrane risk of bias tool.

Eighteen RCTs involving 6,493 patients with average follow-up of 32 weeks were identified and analyzed. DPP-4i plus insulin showed greater reduction in HbA1c than insulin alone (WMD -0.52%, 95% CI -0.61 to -0.43; P<0.0001) (Figure 1).

In conclusion, compared with use of insulin alone, DPP-4i in combination with insulin can significantly lower HbA1c levels in T2DM patients. Further analysis is needed to better understand effects of this combination therapy on other outcomes, such as hypoglycemia and insulin.


J. Yang: None. Q. Tian: None. Y. Tang: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc.. Employee; Spouse/Partner; GlaxoSmithKline plc.. Stock/Shareholder; Spouse/Partner; GlaxoSmithKline plc. A.K. Shah: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc. R. Zhang: Employee; Self; Merck Sharp & Dohme Corp. G. Chen: Employee; Self; Merck Sharp & Dohme Corp.. Y. Zhang: None. S. Rajpathak: Employee; Self; Merck & Co., Inc. T. Hong: Advisory Panel; Self; Novo Nordisk A/S, AstraZeneca.

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