Glucagon‐like peptide‐1 receptor agonists and sodium‐glucose co‐transporter‐2 inhibitors as combination therapy for type 2 diabetes: A systematic review and meta‐analysis
Abstract
Aim To assess the efficacy and safety of combination therapy with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) and a sodium-glucose co-transporter-2 inhibitor (SGLT2i) in patients with type 2 diabetes. Methods We searched Medline, Embase, the Cochrane Library and grey literature sources up to 2 December 2019 for randomized controlled trials in adults with type 2 diabetes assessing the combination of GLP-1RA and SGLT2i, either as co-initiation therapy or as add-on to each other, against placebo or an active comparator. The primary outcome was change in HbA 1c . Secondary outcomes included change in body weight, blood pressure and estimated glomerular filtration rate, and incidence of severe hypoglycaemia, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke and hospitalization for heart failure. We pooled data using random effects meta-analyses. Results Seven trials (1913 patients) were eligible. Compared with GLP-1RA, GLP-1RA/SGLT2i combination therapy was associated with a greater reduction in HbA1c (weighted mean difference -0.61%, 95% CI -1.09% to -0.14%, four studies), body weight (-2.59 kg, -3.68 to -1.51 kg, three studies) and systolic blood pressure (-4.13 mmHg, -7.28 to -0.99 mmHg, four studies). Compared with SGLT2i, GLP-1RA/SGLT2i combination therapy reduced HbA1c (-0.85%, -1.19% to -0.52%, six studies) and systolic blood pressure (-2.66 mmHg, -5.26 to -0.06 mmHg, six studies), but not body weight (-1.46 kg, -2.94 to 0.03 kg, five st…
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In patients with NAFLD, 13 weeks of IONIS-DGAT2Rx reduced PDFF by 4.2%.
“| Loomba et al. | IONIS-DGAT2Rx | NAFLD* | PDFF -4.2 % | ↔ | ↔ | ↔ | NR |”
From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [228]
In patients with NAFLD, 13 weeks of IONIS-DGAT2Rx did not change body weight.
“| Loomba et al. | IONIS-DGAT2Rx | NAFLD* | PDFF -4.2 % | ↔ | ↔ | ↔ | NR |”
From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [228]
Treatment effects of IONIS-DGAT2Rx were comparable to those of TVB-2640.
“The treatment effects of IONIS-DGAT2Rx were comparable to those of TVB-2640 (Table 1) [228].”
From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [228]
Several smaller short-term trials reported additive effects of GLP-1 receptor agonists and SGLT2 inhibitors on surrogate outcomes such as body weight, blood pressure and HbA1c.
“Several smaller short-term trials reported additive effects of GLP-1 RAs and SGLT2i on surrogate outcomes such as body weight, blood pressure and HbA1c18–21.”
From Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial (2024) · cites this paper as [21]
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- Authors
- Mantsiou, C., Karagiannis, T., Kakotrichi, P., Malandris, K., Avgerinos, I., Liakos, A., Tsapas, A., & Bekiari, E.
- Affiliations
- Aristotle University of Thessaloniki (GR)
- Clinical Research and Evidence‐Based Medicine Unit, Second Medical Department Aristotle University of Thessaloniki Thessaloniki Greece
- Corresponding author
- Mantsiou, Chrysanthi
- ORCID
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2020-07-14
- Volume
- 22
- Issue
- 10
- Pages
- 1857-1868
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W3032535508
- Cited by
- 98
- References
- 11
- Citations by year
- 2026: 12 · 2025: 20 · 2024: 26 · 2023: 13 · 2022: 14 · 2021: 9 · 2020: 4
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- OSF Preprints (OSF Preprints) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- type 2 diabetes, combination therapy, GLP-1 receptor agonists, SGLT2 inhibitors, HbA1c, glycemic control, body weight, systolic blood pressure, estimated glomerular filtration rate, hypoglycemia, cardiovascular outcomes, heart failure hospitalization, drug safety, adverse events, drug interactions, adjunctive therapy
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Sodium-Glucose Transporter 2 Inhibitors, Diabetes Mellitus, Type 2, Glucose, Humans, Hypoglycemic Agents, Sodium, Symporters
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