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Cited by 29Diabetes Treatment and ManagementDiabetes Management and ResearchDiabetes and associated disorders

Sodium-glucose cotransporter 2 inhibitors as an add-on therapy to insulin for type 1 diabetes mellitus: meta-analysis of randomized controlled trials

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Rao, Lunwen, Ren, Chenhong, Luo, Shan, Huang, Chenghu, Li, Xuefeng·2021·Acta Diabetologica
DOI 10.1007/s00592-021-01686-xPMC PMC8187227
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Abstract

Aims: The aim was to systematically review the efficacy and safety of sodium–glucose cotransporter inhibitor (SGLT2i) as an adjunct to insulin at different follow-up durations in randomized, double-blind clinical trials in patients with type 1 diabetes. Methods: We conducted a search on Medline, Embase, and the Cochrane Library for relevant studies published before May 2020. According to the duration of follow-up, the subgroup analysis included four periods: 1–4, 12–18, 24–26, and 52 weeks. In the five trials included both 24–26 and 52 weeks of follow-up, we compared the efficacy by the placebo-subtracted difference and changes in SGLT2i groups. Results: Fifteen trials including 7109 participants were analyzed. The combination of SGLT2i and insulin improved hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), daily insulin dose, body weight, and blood pressure, which varied greatly by different follow-ups. Compared with %HbA1c at 24–26 weeks, placebo-subtracted differences and changes in the SGLT2i groups slightly increased. SGLT2i plus insulin treatment showed no difference in the occurrence of urinary tract infections (UTIs), hypoglycemia, or severe hypoglycemia but increased the risk of genital tract infections (GTIs) in a duration-dependent manner. SGLT2i treatment was associated with a significantly higher rate of ketone-related SAEs and diabetic ketoacidosis (DKA) at 52 weeks. Conclusion: SGLT2i as an add-on therapy to insulin improved glycemic control and body weight and decreased the required dose of insulin without increasing the risk of hypoglycemia. However, after 6 months the benefits of SGLT2is on glycemic control may weaken and the risks of GTIs and DKA increased.

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  • SGLT2 inhibitors have been studied in clinical trials in people with type 1 diabetes, and results showed improvements in A1C, reduced body weight, and improved blood pressure; however, SGLT2 inhibitor use in type 1 diabetes was associated with an increased rate of DKA.

    “Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been studied in clinical trials in people with type 1 diabetes, and results showed improvements in A1C, reduced body weight, and improved blood pressure (78); however, SGLT2 inhibitor use in type 1 diabetes was associated with an increased rate of DKA (79).”

    From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [78]

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Sorted by citations

Authors
Rao, L., Ren, C., Luo, S., Huang, C., & Li, X.
Affiliations
  • Hubei University of Medicine (CN)
  • People's Hospital of Bishan District (CN)
Corresponding author
  • Huang, Chenghu
  • Li, Xuefeng
ORCID
Venue
Acta Diabetologica
Publisher
Springer Science and Business Media LLC
Published
2021-03-02
Volume
58
Issue
7
Pages
869-880
ISSN
  • 0940-5429 (ISSN-L)
  • 1432-5233
DOI
10.1007/s00592-021-01686-x
PMC
PMC8187227
OpenAlex
W3135579416
Cited by
29
References
11
Citations by year
2026: 8 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 3
FWCI
0.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Diabetologica (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Natural Science Foundation of Hubei Province (D20182104)
  • The initial project for post-graduates of Hubei University of Medicine (2016QDJZR08)
  • The scientific and technological project of Shiyan City of Hubei Province (16K67)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
SGLT2 inhibitors, type 1 diabetes, insulin add-on therapy, glycemic control, HbA1c, insulin dose reduction, body weight, urinary tract infection, genital tract infection, diabetic ketoacidosis, hypoglycemia
MeSH terms
Sodium-Glucose Transporter 2 Inhibitors, Body Weight, Diabetes Mellitus, Type 1, Double-Blind Method, Drug Therapy, Combination, Glycated Hemoglobin, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Randomized Controlled Trials as Topic, Diabetic Ketoacidosis

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