Trial reportDiabetes, obesity & metabolism2021
Combined exenatide and dapagliflozin has no additive effects on reduction of hepatocellular lipids despite better glycaemic control in patients with type 2 diabetes mellitus treated with metformin: EXENDA, a 24-week, prospective, randomized, placebo-controlled pilot trial.
Trial report in Diabetes, obesity & metabolism, 2021. The graph read 2 numbers from its abstract, feeding 4 cells of the map: it . It reports registered trial NCT03007329. Cited by 30 papers, 7 of them syntheses that pooled it.
What it found
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HbA1c (EXE + DAPA -17.8 mmol/mol, [95% CI -24.8, -10.8], P <0.001; PLAC + DAPA -6.9 mmol/mol, [95% CI -10.5, -3.3], P = 0.001) and fasting glucose significantly decreased in both groups, although EXE + DAPA achieved better glycaemic control than PLAC + DAPA (adjusted difference: HbA1c -6.0 mmol/mol [95% CI -9.7, -2.2], P < 0.01).
Read, but not usablea number the graph found but could not read as for or against
Inclusion criteria were glycated haemoglobin (HbA1c) 48 to 97 mmol/mol (6.5-11%), age 18 to 75 years, body mass index (BMI) ≥25 kg/m RESULTS: After 24 weeks, HCLs were reduced in both treatment groups (absolute change from baseline: EXE + DAPA -4.4%, 95% confidence interval [CI] -8.2, -0.7, P < 0.05; PLAC + DAPA -3.9%, 95% CI -6.0, -1.7, P < 0.01; relative change: EXE + DAPA -35.6%, PLAC + DAPA -32.3%) with no difference between groups.
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What it adds to each cell
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GLP-1 receptor agonists×glycemic control
No readable resultOpen on the map →What to test next →40 readable studies in this cell: 96 favour the treatment, 17 find no difference, 10 favour the comparator.
SGLT2 inhibitors×glycemic control
No readable resultOpen on the map →What to test next →40 readable studies in this cell: 81 favour the treatment, 11 find no difference, 4 favour the comparator.
GLP-1 receptor agonists×adverse events & safety
No readable resultOpen on the map →What to test next →40 readable studies in this cell: 47 favour the treatment, 14 find no difference, 2 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.
SGLT2 inhibitors×adverse events & safety
No readable resultOpen on the map →What to test next →38 readable studies in this cell: 18 favour the treatment, 19 find no difference, 1 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.
A 24 Week Monocentric Prospective Randomized, Placebo-controlled Trial to Evaluate Efficacy of Combination of Exenatide and Dapagliflozin Compared to Dapagliflozin and Placebo and Its Effects on Hepatic, Myocardial and Pancreatic Fat Distribution in Patients With Uncontrolled Type 2 Diabetes Mellitus.
Open the trial in the graphWho cites it
30 citing papers in PubMed, 7 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- Efficacy of Weight-Lowering Agents on Fat Distribution: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Pooled it
- Comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging in patients with type 2 diabetes mellitus: systematic review and network meta-analysis.Hormones (Athens, Greece) · 2023Pooled it
- Impact of tofogliflozin on hepatic outcomes: a systematic review.European journal of clinical pharmacology · 2023Pooled it
- The Effects of Sodium-Glucose Cotransporter 2-Inhibitors on Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease or Steatohepatitis and Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials.Medicina (Kaunas, Lithuania) · 2023Pooled it
- Comparing the effectiveness of long-term use of daily and weekly glucagon-like peptide-1 receptor agonists treatments in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus: a network meta-analysis.Frontiers in endocrinology · 2023Pooled it
- Pooled it
- Effect of glucagon-like peptide-1 receptor agonists on fat distribution in patients with type 2 diabetes: A systematic review and meta-analysis.Journal of diabetes investigation · 2022 · on this mapPooled it
- Dapagliflozin plus exenatide on patients with type 2 diabetes awaiting bariatric surgery in the DEXBASU study.Scientific reports · 2022Trial
- Combined exenatide and dapagliflozin has no additive effects on reduction of hepatocellular lipids despite better glycaemic control in patients with type 2 diabetes mellitus treated with metformin: EXENDA, a 24-week, prospective, randomized, placebo-controlled pilot trial.Diabetes, obesity & metabolism · 2021 · on this mapTrial
- SGLT-2 Inhibitors and GLP-1 Receptor Agonists as Combination Therapy in Type 2 Diabetes.Current diabetes reports · 2026Review
- Pharmacotherapy in metabolic-dysfunction-associated steatotic liver disease: an updated review of the past, present and a promising future.Diabetology international · 2025Article
- Metabolic Dysfunction-Associated Steatotic Liver Disease: A Silent Driver of Cardiovascular Risk and a New Target for Intervention.International journal of molecular sciences · 2025Review
- Efficacy and Safety of Tirzepatide Compared with GLP-1 RAs in Patients with Type 2 Diabetes Treated with Basal Insulin: A Network Meta-analysis.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2025Article
- The effects of gender-affirming hormone therapy on myocardial, hepatic, pancreatic lipid content, body fat distribution and other cardiometabolic risk factors: A magnetic resonance-based study in transgender individuals.Journal of clinical & translational endocrinology · 2025Article
- Safety, efficacy, and cardiovascular benefits of combination therapy with SGLT-2 inhibitors and GLP-1 receptor agonists in patients with diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.Diabetology & metabolic syndrome · 2025Review
- Current Status of Glucagon-like Peptide-1 Receptor Agonists in Metabolic Dysfunction-associated Steatotic Liver Disease: A Clinical Perspective.Journal of clinical and translational hepatology · 2025Review
- SGLT2 inhibitors as metabolic modulators: beyond glycemic control in type 2 diabetes.Frontiers in endocrinology · 2025Review
- Sex differences in ectopic lipid deposits and cardiac function across a wide range of glycemic control: a secondary analysis.Obesity (Silver Spring, Md.) · 2024Article
- Pharmacological Approaches to Nonalcoholic Fatty Liver Disease: Current and Future Therapies.Diabetes spectrum : a publication of the American Diabetes Association · 2024Article
- The role of anti-diabetic drugs in NAFLD. Have we found the Holy Grail? A narrative review.European journal of clinical pharmacology · 2024Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The marked sentences are the ones the graph read a number from.
aimsTo investigate the potential synergistic effects of combined exenatide (EXE) and dapagliflozin (DAPA) versus (PLAC) placebo and DAPA on hepatocellular lipid (HCL) reduction after 24 weeks of treatment. MATERIALS AND
methodsThirty patients with type 2 diabetes were randomized to weekly EXE and daily DAPA (n = 16) or weekly PLAC and daily DAPA (n = 14). Inclusion criteria were glycated haemoglobin (HbA1c) 48 to 97 mmol/mol (6.5-11%), age 18 to 75 years, body mass index (BMI) ≥25 kg/m
resultsAfter 24 weeks, HCLs were reduced in both treatment groups (absolute change from baseline: EXE + DAPA -4.4%, 95% confidence interval [CI] -8.2, -0.7, P < 0.05; PLAC + DAPA -3.9%, 95% CI -6.0, -1.7, P < 0.01; relative change: EXE + DAPA -35.6%, PLAC + DAPA -32.3%) with no difference between groups. Similar findings were observed for subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). HbA1c (EXE + DAPA -17.8 mmol/mol, [95% CI -24.8, -10.8], P <0.001; PLAC + DAPA -6.9 mmol/mol, [95% CI -10.5, -3.3], P = 0.001) and fasting glucose significantly decreased in both groups, although EXE + DAPA achieved better glycaemic control than PLAC + DAPA (adjusted difference: HbA1c -6.0 mmol/mol [95% CI -9.7, -2.2], P < 0.01). Body weight was reduced in both treatment groups (EXE + DAPA -7.3 kg, 95% CI -9.9, -4.8, P <0.001; PLAC + DAPA -4.6 kg, 95% CI -7.4, -1.8, P <0.01) with comparable results between groups. Changes in HCLs and weight, hip and waist circumference, VAT and SAT were positively associated.
conclusionAfter 24 weeks, HCLs were significantly but comparably reduced in the EXE + DAPA and PLAC + DAPA groups, despite significantly better glycaemic control in the combined group EXE + DAPA. Changes in HCLs were associated with weight loss and reduction of visceral adiposity, but not with glucose control. Further studies are necessary to evaluate possible additional long-term effects of a combined treatment.
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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.