SynthesisMedicine2026
Triple oral therapy combining metformin, SGLT-2 and DPP-4 inhibitors versus dual therapy in type 2 diabetes mellitus: A systematic review and meta-analysis.
Synthesis in Medicine, 2026. The graph read 1 number from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. Not yet cited in PubMed.
What it found
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Triple therapy resulted in greater reduction in fasting plasma glucose, with an SMD of -0.30 (95% CI: -0.62 to 0.01; P = .06).
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Where it lands on the map
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What it adds to each cell
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Diet, exercise & lifestyle×glycemic control
No readable resultOpen on the map →What to test next →5 readable studies in this cell: 3 favour the treatment, 2 find no difference, 0 favour the comparator.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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backgroundTriple oral therapy combining metformin, sodium-glucose cotransporter 2 inhibitor, and a dipeptidyl peptidase-4 inhibitor has been proposed as a synergistic approach to intensify glycemic control in patients with type 2 diabetes mellitus. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of triple therapy compared to dual therapy (metformin plus either sodium-glucose cotransporter 2 or dipeptidyl peptidase-4 inhibitor).
methodsFollowing preferred reporting items for systematic review and meta-analysis guidelines, we searched PubMed, Embase, Scopus, and Web of Science through January 2026. Studies included randomized controlled trials comparing triple versus dual therapy in adults with type 2 diabetes mellitus. Outcomes included hemoglobin A1c (HbA1c), fasting plasma glucose, body weight, achievement of HbA1c < 7%, and adverse events (AEs). Pooled standardized mean differences (SMDs) and risk ratios (RRs) were calculated using random-effects models.
resultsEight studies encompassing 2606 participants were included. Findings indicate triple therapy significantly reduced HbA1c levels compared to dual therapy, with a SMD of - 0.54 (95% confidence interval [CI]: -0.92 to -0.16; P = .005). Triple therapy resulted in greater reduction in fasting plasma glucose, with an SMD of -0.30 (95% CI: -0.62 to 0.01; P = .06). Patients on triple therapy were more likely to achieve HbA1c levels below 7% (RR: 2.02; 95% CI: 1.55-2.63; P < .0001). Weight reduction was modest, with an SMD: -0.14 (95% CI: -0.22 to -0.07; P = .0002). No significant differences were found in total AEs (RR = 0.97; P = .69) or hypoglycemia (RR = 1.32; P = .32), although there was higher discontinuation due to AEs (RR = 2.62; P = .03).
conclusionTriple therapy offers superior glycemic control over dual therapy without major safety trade-offs, though tolerability may affect long-term adherence.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.