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.

Abdul Fatah Malik, Fnu Kashish, Fnu Shivani, Somesh Kumar, Vanesha Kumari, Abdul Haseeb, Ahmad Mujtaba, Abdur Raheem, Syed Muhammad Sinaan Ali, Usama Saleh and 1 more

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

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.

1number the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

Read, but not usablea number the graph found but could not read as for or against

Glycemic controlcomparator not stated · t2dfeeds one cell of the map
reduction -0.30-0.62 to 0.01P = .06
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).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

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.

Belief with this paper
0.99replicated · 2 families support, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

11 authors.

Abdul Fatah MalikDepartment of Medicine, Bilawal Medical College, LUMHS, Jamshoro, Pakistan.
Fnu KashishDepartment of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan.
Fnu ShivaniDepartment of Medicine, Ascension Saint Jospeh Hospital, Chicago, IL.
Somesh KumarDepartment of Medicine, Khairpur Medical College, Khairpur Mir's, Pakistan.
Vanesha KumariDepartment of Medicine, Ghulam Muhammad Mahar Medical College, Sukkur, Pakistan.
Abdul HaseebDepartment of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan.
Ahmad MujtabaDepartment of Medicine, Liaquat National Hospital and Medical College, Karachi, Pakistan.
Abdur RaheemDepartment of Medicine, Baqai Medical College, Karachi, Pakistan.
Syed Muhammad Sinaan AliDepartment of Medicine, Liaquat National Hospital and Medical College, Karachi, Pakistan.
Usama SalehDepartment of Medicine, Dow International Medical College, Karachi, Pakistan.
Tagwa Kalool Fadlalla AhmadDepartment of Medicine, Ahfad University of Women, Omdurman, Sudan.ORCID 0009-0005-3942-9554

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

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.

Indexed as

Diabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsHypoglycemic AgentsMetforminSodium-Glucose Transporter 2 InhibitorsAdministration, OralBlood GlucoseDrug Therapy, CombinationGlycated HemoglobinHumansRandomized Controlled Trials as TopicBlood GlucoseDipeptidyl-Peptidase IV InhibitorsGlycated HemoglobinHypoglycemic AgentsMetforminSodium-Glucose Transporter 2 InhibitorsDPP-4 inhibitorsfasting blood glucoseHbA1cmetforminSGLT-2 inhibitorstype 2 diabetes mellitus

Identifiers

PMID42216339
PMCPMC13225597

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.