ArticlePloS one2018
Comparison of antidiabetic drugs added to sulfonylurea monotherapy in patients with type 2 diabetes mellitus: A network meta-analysis.
Article in PloS one, 2018. The graph read 6 numbers from its abstract, feeding 6 cells of the map: it finds no clear difference in 1. Cited by 10 papers, 3 of them syntheses that pooled 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.
Ratios
Compared with GLP-1RA, all agents were associated with a lower risk of hypoglycemia, except Met [OR, 0.58 (95% CI: 0.29 to 1.18)] and basal insulin [OR, 0.76 (95% CI: 0.27 to 2.17)], which appeared to have no significant effects on the risk of hypoglycemia ( Table 2 and Fig 3 ).
Compared with placebo, all treatment regimens were associated with a significantly higher risk of hypoglycemia, except the combinations of SU plus sodium-glucose co-transporter-2 inhibitor (SGLT-2i) [OR, 1.35 (95% CI: 0.81 to 2.25)] or alpha-glucosidase inhibitor (AGI) [OR, 1.16 (95% CI: 0.55 to 2.44)].
Compared with placebo, all treatment regimens were associated with a significantly higher risk of hypoglycemia, except the combinations of SU plus sodium-glucose co-transporter-2 inhibitor (SGLT-2i) [OR, 1.35 (95% CI: 0.81 to 2.25)] or alpha-glucosidase inhibitor (AGI) [OR, 1.16 (95% CI: 0.55 to 2.44)].
Differences
In comparisons of second-line agents, SGLT-2i, GLP-1RA, and AGI more significantly reduced body weight versus TZD, Met, and DPP-4i, with changes ranging from -2.91 kg (95% CI: -4.15 to -1.68) for SGLT-2i versus TZD to -1.30 kg (95% CI: -1.98 to -0.62) for AGI versus DPP-4i.
In comparisons of other antidiabetic drugs, the significant differences ranged from a reduction of -0.30% (95% CI: -0.55 to -0.05) for basal insulin versus DPP-4i to -0.49% (95% CI: -0.64 to -0.34) for GLP-1RA versus TZD ( S12 Table ).
Direct pairwise meta-analyses (versus placebo) showed significant reductions in FPG with all second-line agents combined with SU, ranging from -2.77 mmol/l (95% CI: -4.14 to -1.40) for TZD to -0.62 mmol/l (95% CI: -0.78 to -0.47) for DPP-4i.
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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.
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.
Other glucose-lowering×hypoglycaemia
InconclusiveOpen on the map →What to test next →1 readable study in this cell: 1 favour the treatment, 0 find no difference, 0 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
Sulfonylureas & glinides×hypoglycaemia
No readable resultOpen on the map →What to test next →10 readable studies in this cell: 0 favour the treatment, 1 find no difference, 9 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
Metformin×body weight & composition
No readable resultOpen on the map →What to test next →19 readable studies in this cell: 7 favour the treatment, 6 find no difference, 6 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
Metformin×hypoglycaemia
No readable resultOpen on the map →What to test next →1 readable study in this cell: 0 favour the treatment, 1 find no difference, 0 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
Other glucose-lowering×glycemic control
No readable resultOpen on the map →What to test next →8 readable studies in this cell: 5 favour the treatment, 0 find no difference, 3 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
Sulfonylureas & glinides×glycemic control
No readable resultOpen on the map →What to test next →31 readable studies in this cell: 7 favour the treatment, 13 find no difference, 11 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
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.
Who cites it
10 citing papers in PubMed, 3 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- Comparative efficacy of dietary interventions for overweight or obese adults with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials.Frontiers in nutrition · 2026Pooled it
- Effects of different hypoglycaemic drugs on beta-cell function in type 2 diabetes mellitus: a systematic review and network meta-analysis.European journal of medical research · 2025Pooled it
- Comparative analysis of the efficacies of probiotic supplementation and glucose-lowering drugs for the treatment of type 2 diabetes: A systematic review and meta-analysis.Frontiers in nutrition · 2022Pooled it
- Comparative safety of sulfonylurea therapies on cardiovascular and severe hypoglycemia outcomes among adults with type 2 diabetes and moderate cardiovascular risk: a target trial emulation.BMJ open diabetes research & care · 2026Article
- ADD2Dia: Real-World Clinical Effectiveness of Adding a Sodium-Glucose Cotransporter 2 Inhibitor to Gliclazide-Based Therapy in Type 2 Diabetes.Advances in therapy · 2025Article
- The Role of Real-World Evidence in Treatment Decision-Making, Regulatory Assessment, and Understanding the Perspectives of People with Type 2 Diabetes: Examples with Gliclazide MR.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2023Article
- Prevalence and predictors of clinical inertia in patients with type 2 diabetes who were treated with a single oral antidiabetic drug.Journal of diabetes investigation · 2023Article
- Efficacy and Safety of Ertugliflozin in Patients With Diabetes Mellitus Inadequately Controlled by Sulfonylurea Monotherapy: a Substudy of VERTIS CV.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2021Article
- Prescription of Sulphonylureas among Patients with Type 2 Diabetes Mellitus in Italy: Results from the Retrospective, Observational Multicentre Cross-Sectional SUSCIPE (Sulphonyl_UreaS_Correct_Internal_Prescription_Evaluation) Study.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2020Article
- The Place of Sulfonylureas in the Evolving Landscape of Combination Therapy.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
aimsThis study aimed to investigate the efficacy and safety of dual therapy comprising sulfonylurea (SU) plus antidiabetic drugs for the treatment of type 2 diabetes mellitus (T2DM).
methodsWe searched the PubMed, Cochrane library, and Embase databases for randomized clinical trials (≥24 weeks) published up to December 28, 2017. Subsequently, we conducted pairwise and network meta-analyses to calculate the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) of the outcomes.
resultsThe final analyses included 24 trials with a total of 10,032 patients. Compared with placebo, all treatment regimens were associated with a significantly higher risk of hypoglycemia, except the combinations of SU plus sodium-glucose co-transporter-2 inhibitor (SGLT-2i) [OR, 1.35 (95% CI: 0.81 to 2.25)] or alpha-glucosidase inhibitor (AGI) [OR, 1.16 (95% CI: 0.55 to 2.44)]. Notably, the combination of SU plus glucagon-like peptide-1 receptor agonist (GLP-1RA) was associated with the most significant increase in the risk of hypoglycemia. Furthermore, all SU-based combination regimens reduced the glycated hemoglobin (HbA1c) and fasting plasma glucose levels (FPG). However, only combinations containing SGLT-2i [MD, -1.00 kg (95% CI: -1.73 to -0.27)] and GLP-1RA [MD, -0.56 kg (95% CI: -1.10 to -0.02)] led to weight loss.
conclusionsOur findings highlight the importance of considering the risk of hypoglycemia when selecting antidiabetic drugs to be administered concomitantly with SU. Although all classes of antidiabetic drugs improved glucose control when administered in combination with SU, SGLT-2i might be the best option with respect to factors such as hypoglycemia and body weight.
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What Socratic holds
Registered trials
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.