Trial reportAdvances in therapy2015
Efficacy and safety of linagliptin co-administered with low-dose metformin once daily versus high-dose metformin twice daily in treatment-naïve patients with type 2 diabetes: a double-blind randomized trial.
Trial report in Advances in therapy, 2015. The graph read 3 numbers from its abstract, feeding 4 cells of the map, but none could be read as for or against, so it casts no vote. Cited by 8 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.
Read, but not usablea number the graph found but could not read as for or against
RESULTS: At Week 14, HbA1c changed from a mean baseline of 8.0% (64 mmol/mol) by -0.99% (-11 mmol/mol) for linagliptin + LD metformin, and -0.98% (-11 mmol/mol) for HD metformin [treatment difference -0.01% (95% confidence interval -0.13, 0.12) (0 mmol/mol), P = 0.8924].
RESULTS: At Week 14, HbA1c changed from a mean baseline of 8.0% (64 mmol/mol) by -0.99% (-11 mmol/mol) for linagliptin + LD metformin, and -0.98% (-11 mmol/mol) for HD metformin [treatment difference -0.01% (95% confidence interval -0.13, 0.12) (0 mmol/mol), P = 0.8924].
RESULTS: At Week 14, HbA1c changed from a mean baseline of 8.0% (64 mmol/mol) by -0.99% (-11 mmol/mol) for linagliptin + LD metformin, and -0.98% (-11 mmol/mol) for HD metformin [treatment difference -0.01% (95% confidence interval -0.13, 0.12) (0 mmol/mol), P = 0.8924].
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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.
DPP-4 inhibitors×glycemic control
No readable resultOpen on the map →What to test next →40 readable studies in this cell: 59 favour the treatment, 19 find no difference, 24 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.
DPP-4 inhibitors×adverse events & safety
No readable resultOpen on the map →What to test next →34 readable studies in this cell: 12 favour the treatment, 17 find no difference, 5 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×glycemic control
No readable resultOpen on the map →What to test next →40 readable studies in this cell: 41 favour the treatment, 13 find no difference, 7 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×adverse events & safety
No readable resultOpen on the map →What to test next →22 readable studies in this cell: 9 favour the treatment, 8 find no difference, 5 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
8 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- A systematic review and meta-analysis of the relative benefit of dual versus single oral hypoglycaemic therapy following diagnosis with type 2 diabetes (T2D).Diabetic medicine : a journal of the British Diabetic Association · 2026 · on this mapPooled it
- Dipeptidyl peptidase-4 inhibitors and gallbladder or biliary disease in type 2 diabetes: systematic review and pairwise and network meta-analysis of randomised controlled trials.BMJ (Clinical research ed.) · 2022Pooled it
- Role of metformin in overweight and obese people without diabetes: a systematic review and network meta-analysis.European journal of clinical pharmacology · 2019Pooled it
- Randomized clinical trial of the safety and efficacy of sitagliptin and metformin co-administered to Chinese patients with type 2 diabetes mellitus.Journal of diabetes investigation · 2016 · on this mapTrial
- Comparison of gliclazideWorld journal of diabetes · 2022Article
- Influence of Tangeretin on the Exponential Regression of Inflammation and Oxidative Stress in Streptozotocin-Induced Diabetic Nephropathy.Applied biochemistry and biotechnology · 2022Article
- Metformin: A Prospective Alternative for the Treatment of Chronic Pain.Frontiers in pharmacology · 2020Review
- Efficacy and Safety of Initial Combination Therapy in Treatment-Naïve Type 2 Diabetes Patients: A Systematic Review and Meta-analysis.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
introductionThe aim of this study was to investigate the efficacy and safety of linagliptin + low-dose (LD) metformin once daily versus high-dose (HD) metformin twice daily in treatment-naïve patients with type 2 diabetes.
methodsPatients (n = 689) were randomized (1:1) to double-blind treatment with linagliptin 5 mg + LD metformin (1000 mg) or HD metformin (2000 mg) for 14 weeks. Metformin was initiated at 500 mg/day and up-titrated within 2 weeks; the dose then remained unchanged. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to Week 14 in patients who tolerated a daily metformin dose of ≥1000 mg after 2 weeks.
resultsAt Week 14, HbA1c changed from a mean baseline of 8.0% (64 mmol/mol) by -0.99% (-11 mmol/mol) for linagliptin + LD metformin, and -0.98% (-11 mmol/mol) for HD metformin [treatment difference -0.01% (95% confidence interval -0.13, 0.12) (0 mmol/mol), P = 0.8924]. The proportion of patients who achieved HbA1c <7.0% (53 mmol/mol) without occurrence of moderate or severe gastrointestinal (GI) events (including abdominal pain, nausea, vomiting, diarrhea, and decreased appetite) was the same in both groups (51.3% for both). Although the occurrence of moderate or severe GI events was similar, the linagliptin + LD metformin group had fewer mild GI events (18.5% versus 24.3%). The incidence of hypoglycemia was low in both groups.
conclusionLinagliptin + LD metformin combination showed similar efficacy and safety to HD metformin. This combination may be an alternative treatment option in patients who may have difficulty tolerating metformin doses >1000 mg/day.
fundingBoehringer Ingelheim.
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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.