Early combination therapy for the treatment of type 2 diabetes mellitus: systematic review and meta‐analysis. Issue 5 (16th December 2013)

• Record Type: Journal Article
• Authors: Phung, O. J.; Sobieraj, D. M.; Engel, S. S.; Rajpathak, S. N.
• Is Part Of: Diabetes, obesity & metabolism. Volume 16:Issue 5(2014:May)
• Page Start: 410
• Page End: 417
• Publication Date: 2013-12-16
• Subjects: Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.12233
• Languages: English
• ISSNs: 1462-8902

Abstract

<abstract abstract-type="main" id="dom12233-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="dom12233-sec-0001" sec-type="section"> <title>Aims</title> <p id="dom12233-para-0001">Guidelines for type 2 diabetes recommend add‐on agents when metformin alone fails to provide adequate glycaemic control. However, early combination therapy may benefit health outcomes. We conducted a systematic review and meta‐analysis to investigate this question.</p> </sec> <sec id="dom12233-sec-0002" sec-type="section"> <title>Methods</title> <p id="dom12233-para-0002">We searched MEDLINE and Cochrane CENTRAL (up to July 2012) without language restrictions. We sought randomized controlled trials (RCTs) evaluating initial combination therapy with metformin versus metformin monotherapy in patients with untreated type 2 diabetes. Weighted mean differences (WMDs) for changes from baseline and relative risks (RRs) [with 95% confidence intervals (CIs)] were calculated using random‐effects model.</p> </sec> <sec id="dom12233-sec-0003" sec-type="section"> <title>Results</title> <p id="dom12233-para-0003">In 15 RCTs (N = 6693), the mean age range was 48.4–62.7 years; mean baseline glycosylated haemoglobin (A1c) was 7.2–9.9% and mean diabetes duration was 1.6–4.1 years, with median follow‐up of 6 months and with 13 comparisons for A1c change, 14 comparisons for A1c goal attainment of <7% and 13 comparisons for change in fasting plasma glucose (FPG). Drugs combined with metformin included thiazolidinediones (TZDs), insulin secretagogues, dipeptidyl peptidase‐4 (DPP‐4) inhibitors or sodium glucose transporterase (SGLT‐2) inhibitors. Compared to metformin alone, combination therapy with metformin provided statistically significant reductions in A1c (WMD −0.43%, 95% CI −0.56, −0.30), increases in attainment of A1c goal of less than 7% (RR 1.40, 95% CI 1.33–1.48) and reductions in FPG (WMD −14.30 mg/dl, 95% CI −16.09, −12.51).</p> </sec> <sec id="dom12233-sec-0004" sec-type="section"> <title>Conclusions</title> <p id="dom12233-para-0004">These results suggest a potential benefit of initial combination therapy on glycaemic outcomes in diabetes compared to metformin monotherapy across a wide range of baseline A1c levels. Further research should explore if early combination treatment may also affect longer term health outcomes in diabetes.</p> </sec> </abstract>