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Efficacy of DPP-4 Inhibitors and Metformin as Initial Combo Therapy in Type 2 Diabetes

DPP-4 may be a credible alternative for patients unable to tolerate metformin….

The goal for this meta-analysis study was to provide an update on the efficacy and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes.

The researchers looked at these medications as first line treatments because of their popularity among diabetics for adjunct therapy on top of other medication regimens.

The study was performed by utilizing a search on MEDLINE, Embase and Cochrane Collaborative database for randomized controlled trials of DPP-4 inhibitors and metformin as initial combination therapy or as metformin monotherapy in patients with type 2 diabetes. The majority of the data was taken in December 2012 and included medications such as: alogliptin, dutogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin, and metformin.

All randomized controlled trials were selected for meta-analysis if they specifically compared DPP-4 inhibitors plus metformin as initial combination therapy or DPP-4 inhibitor monotherapy to metformin monotherapy. The second inclusion parameter used in the study took into consideration the duration of treatment. All trials incorporated into the study had to be greater than 12 weeks to be included. A final reporting criteria for the medication study was the reported data on HbA1c change, fasting plasma glucose change, weight change, adverse cardiovascular events, hypoglycemia, or gastrointestinal adverse events.

Results from the review study came from 8 randomized controlled trials. The authors from the study summarized the results as follows from a large comparison of all randomized controlled trial data. Compared to metformin monotherapy, DPP-4 inhibitors monotherapy was associated with lower reduction in HbA1c level [weighted mean differences (MD) =0.28], lower reduction in fasting glucose level MD=0.8, lower weight loss MD=1.51, but lower risk of adverse cardiovascular events (RR)=0.36, lower risk of hypoglycemia RR=0.44 and lower risk of gastrointestinal adverse events RR=0.63.

Compared with metformin monotherapy, DPP-4 inhibitors plus metformin as initial combination therapy was associated with higher reduction in HbA1c level MD=−0.49, higher reduction in fasting plasma glucose levels MD=−0.80, lower weight loss MD=0.44 but was not associated with a further reduction in adverse cardio vascular events RR=0.54, nor the higher risk of hypoglycemia RR=1.04, nor the prolonged risk of gastrointestinal adverse events RR=0.98.

In conclusion, DPP-4 inhibitors, which were safe and effective in controlling the blood glucose, may possibly decrease the risk of cardiovascular events in patients with type 2 diabetes. It could be a credible alternative for type 2 diabetic patients who cannot tolerate metformin, or are in high risk of cardiovascular exposure and complications. High-quality, large sample and long-term follow-up clinical trials are needed to confirm the long-term conclusions, the authors said.

Dan, Wu. "Efficacy and safety of dipeptidyl peptidase-4 inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus: A Meta-analysis." Diabetes, Obesity and Metabolism. 2013 John Wiley & Sons, Inc. January 1 (2013): n. page. Web. 13 Jul. 2013.